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Dr. Chuanbin Shen
University of Toronto

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0 Medicine
0 Thrombosis
0 Toxins
0 platelet
0 integrin ligands

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Journal article
Published: 13 January 2021 in Cardiovascular & Hematological Disorders-Drug Targets
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Platelets are small blood cells known primarily for their ability to adhere and aggregate at injured vessels to arrest bleeding. However, when triggered under pathological conditions, the same adaptive mechanism of platelet adhesion and aggregation may cause thrombosis, a primary cause of heart attack and stroke. Over recent decades, research has made considerable progress in uncovering the intricate and dynamic interactions that regulate these processes. Integrins are heterodimeric cell surface receptors expressed on all metazoan cells that facilitate cell adhesion, movement, and signaling, to drive biological and pathological processes such as thrombosis and hemostasis. Recently, our group discovered that the plexin-semaphorin-integrin (PSI) domains of the integrin β subunits exert endogenous thiol isomerase activity derived from their two highly conserved CXXC active site motifs. Given the importance of redox reactions in integrin activation and its location in the knee region, this PSI domain activity may be critically involved in facilitating the interconversions between integrin conformations. Our monoclonal antibodies against the β3 PSI domain inhibited its thiol isomerase activity and proportionally attenuated fibrinogen binding and platelet aggregation. Notably, these antibodies inhibited thrombosis without significantly impairing hemostasis or causing platelet clearance. In this review, we will update mechanisms of thrombosis and hemostasis, including platelet versatilities and immune-mediated thrombocytopenia, discuss critical contributions of the newly discovered PSI domain thiol isomerase activity, and its potential as a novel target for anti-thrombotic therapies and beyond.

ACS Style

Daniel T. MacKeigan; Tiffany Ni; Chuanbin Shen; Tyler W. Stratton; Wenjing Ma; Guangheng Zhu; Preeti Bhoria; Heyu Ni. Updated Understanding of Platelets in Thrombosis and Hemostasis: The Roles of Integrin PSI Domains and their Potential as Therapeutic Targets. Cardiovascular & Hematological Disorders-Drug Targets 2021, 20, 260 -273.

AMA Style

Daniel T. MacKeigan, Tiffany Ni, Chuanbin Shen, Tyler W. Stratton, Wenjing Ma, Guangheng Zhu, Preeti Bhoria, Heyu Ni. Updated Understanding of Platelets in Thrombosis and Hemostasis: The Roles of Integrin PSI Domains and their Potential as Therapeutic Targets. Cardiovascular & Hematological Disorders-Drug Targets. 2021; 20 (4):260-273.

Chicago/Turabian Style

Daniel T. MacKeigan; Tiffany Ni; Chuanbin Shen; Tyler W. Stratton; Wenjing Ma; Guangheng Zhu; Preeti Bhoria; Heyu Ni. 2021. "Updated Understanding of Platelets in Thrombosis and Hemostasis: The Roles of Integrin PSI Domains and their Potential as Therapeutic Targets." Cardiovascular & Hematological Disorders-Drug Targets 20, no. 4: 260-273.

Journal article
Published: 27 November 2020 in Toxins
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Envenomation by viperid snakes may lead to severe bleeding, consumption coagulopathy, and thrombotic microangiopathy symptoms. The exact etiology or toxins responsible for thrombotic microangiopathy symptoms after snake envenomation remain obscure. Snake C-type lectin-like proteins (snaclecs) are one of the main non-enzymatic protein constituents in viper venoms, of which a majority are considered as modulators of thrombosis and hemostasis. In this study, we demonstrated that two snaclecs (mucetin and stejnulxin), isolated and identified from Protobothrops mucrosquamatus and Trimeresurus stejnegeri venoms, directly induced platelet degranulation and clot-retraction in vitro, and microvascular thrombosis has been confirmed in various organs in vivo. These snaclecs reduced cerebral blood flow and impaired motor balance and spatial memories in mice, which partially represent the thrombotic microangiopathy symptoms in some snakebite patients. The functional blocking of these snaclecs with antibodies alleviated the viper venom induced platelet activation and thrombotic microangiopathy-like symptoms. Understanding the pathophysiology of thrombotic microangiopathy associated with snake envenoming may lead to emerging therapeutic strategies.

ACS Style

Chengbo Long; Ming Liu; Huiwen Tian; Ya Li; Feilong Wu; James Mwangi; Qiumin Lu; Tarek Mohamed Abd El-Aziz; Ren Lai; Chuanbin Shen. Potential Role of Platelet-Activating C-Type Lectin-Like Proteins in Viper Envenomation Induced Thrombotic Microangiopathy Symptom. Toxins 2020, 12, 749 .

AMA Style

Chengbo Long, Ming Liu, Huiwen Tian, Ya Li, Feilong Wu, James Mwangi, Qiumin Lu, Tarek Mohamed Abd El-Aziz, Ren Lai, Chuanbin Shen. Potential Role of Platelet-Activating C-Type Lectin-Like Proteins in Viper Envenomation Induced Thrombotic Microangiopathy Symptom. Toxins. 2020; 12 (12):749.

Chicago/Turabian Style

Chengbo Long; Ming Liu; Huiwen Tian; Ya Li; Feilong Wu; James Mwangi; Qiumin Lu; Tarek Mohamed Abd El-Aziz; Ren Lai; Chuanbin Shen. 2020. "Potential Role of Platelet-Activating C-Type Lectin-Like Proteins in Viper Envenomation Induced Thrombotic Microangiopathy Symptom." Toxins 12, no. 12: 749.

Journal article
Published: 20 August 2020 in Blood
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Several adaptor molecules bind to cytoplasmic tails of β-integrins and facilitate bidirectional signaling, which is critical in thrombosis and hemostasis. Interfering with integrin-adaptor interactions spatially or temporally to inhibit thrombosis without affecting hemostasis is an attractive strategy for the development of safe antithrombotic drugs. We show for the first time that the 14-3-3ζ–c-Src–integrin-β3 complex is formed during platelet activation. 14-3-3ζ–c-Src interaction is mediated by the -PIRLGLALNFSVFYYE- fragment (PE16) on the 14-3-3ζ and SH2-domain on c-Src, whereas the 14-3-3ζ–integrin-β3 interaction is mediated by the -ESKVFYLKMKGDYYRYL- fragment (EL17) on the 14-3-3ζ and -KEATSTF- fragment (KF7) on the β3-integrin cytoplasmic tail. The EL17-motif inhibitor, or KF7 peptide, interferes with the formation of the 14-3-3ζ–c-Src–integrin-β3 complex and selectively inhibits β3 outside-in signaling without affecting the integrin-fibrinogen interaction, which suppresses thrombosis without causing significant bleeding. This study characterized a previously unidentified 14-3-3ζ–c-Src–integrin-β3 complex in platelets and provided a novel strategy for the development of safe and effective antithrombotic treatments.

ACS Style

Chuanbin Shen; Ming Liu; Runjia Xu; Gan Wang; June Li; Pingguo Chen; Wenjing Ma; James Mwangi; Qiumin Lu; Zilei Duan; Zhiye Zhang; Fatima Zohra Dahmani; Daniel Thomas MacKeigan; Heyu Ni; Ren Lai. The 14-3-3ζ–c-Src–integrin-β3 complex is vital for platelet activation. Blood 2020, 136, 974 -988.

AMA Style

Chuanbin Shen, Ming Liu, Runjia Xu, Gan Wang, June Li, Pingguo Chen, Wenjing Ma, James Mwangi, Qiumin Lu, Zilei Duan, Zhiye Zhang, Fatima Zohra Dahmani, Daniel Thomas MacKeigan, Heyu Ni, Ren Lai. The 14-3-3ζ–c-Src–integrin-β3 complex is vital for platelet activation. Blood. 2020; 136 (8):974-988.

Chicago/Turabian Style

Chuanbin Shen; Ming Liu; Runjia Xu; Gan Wang; June Li; Pingguo Chen; Wenjing Ma; James Mwangi; Qiumin Lu; Zilei Duan; Zhiye Zhang; Fatima Zohra Dahmani; Daniel Thomas MacKeigan; Heyu Ni; Ren Lai. 2020. "The 14-3-3ζ–c-Src–integrin-β3 complex is vital for platelet activation." Blood 136, no. 8: 974-988.

Research article
Published: 14 August 2020 in Circulation Research
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Rationale: Epidemiological studies have identified an associate between iron deficiency (ID) and the use of oral contraceptives (CC) and ischemic stroke (IS). To date, however, the underlying mechanism remains poorly understood. Both ID and CC have been demonstrated to upregulate the level and iron-binding ability of Tf (transferrin), with our recent study showing that this upregulation can induce hypercoagulability by potentiating FXIIa/thrombin and blocking antithrombin-coagulation proteases interactions. Objective: To investigate whether Tf mediates IS associated with ID or CC and the underlying mechanisms. Methods and Results: Tf levels were assayed in the plasma of IS patients with a history of ID anemia, ID anemia patients, venous thromboembolism patients using CC, and ID mice, and in the cerebrospinal fluid of some IS patients. Effects of ID and estrogen administration on Tf expression and coagulability and the underlying mechanisms were studied in vivo and in vitro. High levels of Tf and Tf-thrombin/FXIIa complexes were found in patients and ID mice. Both ID and estrogen upregulated Tf through hypoxia and estrogen response elements located in the Tf gene enhancer and promoter regions, respectively. In addition, ID, administration of exogenous Tf or estrogen, and Tf overexpression promoted platelet-based thrombin generation and hypercoagulability and thus aggravated IS. In contrast, anti-Tf antibodies, Tf knockdown, and peptide inhibitors of Tf-thrombin/FXIIa interaction exerted anti-IS effects in vivo. Conclusions: Our findings revealed that certain factors (ie, ID and CC) upregulating Tf are risk factors of thromboembolic diseases decipher a previously unrecognized mechanistic association among ID, CC, and IS and provide a novel strategy for the development of anti-IS medicine by interfering with Tf-thrombin/FXIIa interactions.

ACS Style

Xiaopeng Tang; Mingqian Fang; Ruomei Cheng; Zhiye Zhang; Yuming Wang; Chuanbin Shen; Yajun Han; Qiumin Lu; Yingrong Du; Yingying Liu; Zhaohui Sun; Liping Zhu; James Mwangi; Min Xue; Chengbo Long; Ren Lai. Iron-Deficiency and Estrogen Are Associated With Ischemic Stroke by Up-Regulating Transferrin to Induce Hypercoagulability. Circulation Research 2020, 127, 651 -663.

AMA Style

Xiaopeng Tang, Mingqian Fang, Ruomei Cheng, Zhiye Zhang, Yuming Wang, Chuanbin Shen, Yajun Han, Qiumin Lu, Yingrong Du, Yingying Liu, Zhaohui Sun, Liping Zhu, James Mwangi, Min Xue, Chengbo Long, Ren Lai. Iron-Deficiency and Estrogen Are Associated With Ischemic Stroke by Up-Regulating Transferrin to Induce Hypercoagulability. Circulation Research. 2020; 127 (5):651-663.

Chicago/Turabian Style

Xiaopeng Tang; Mingqian Fang; Ruomei Cheng; Zhiye Zhang; Yuming Wang; Chuanbin Shen; Yajun Han; Qiumin Lu; Yingrong Du; Yingying Liu; Zhaohui Sun; Liping Zhu; James Mwangi; Min Xue; Chengbo Long; Ren Lai. 2020. "Iron-Deficiency and Estrogen Are Associated With Ischemic Stroke by Up-Regulating Transferrin to Induce Hypercoagulability." Circulation Research 127, no. 5: 651-663.

Cellular haemostasis and platelets
Published: 27 July 2020 in Thrombosis and Haemostasis
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Bleeding and thrombocytopenia to readministration are the most serious side effects of clinical integrin αIIbβ3 antagonists such as RGD-containing peptides. Here we show that a non-RGD peptide ZDPI, identified from skin secretions of Amolops loloensis, inhibited platelet aggregation induced by agonists, such as adenosine diphosphate, collagen, arachidonic acid, PAR1AP, and integrin αIIbβ3 allosteric activator, and reduces soluble fibrinogen binding to activated platelets without perturbing adhesion numbers on immobilized fibrinogen. Further study showed that ZDPI preferred to bind to the active conformation of integrin αIIbβ3, and thus inhibited c-Src-mediated integrin signaling transduction. In contrast to currently used clinical blockers of integrin αIIbβ3, which are all conformation-unspecific blockers, ZDPI conformation specifically binds to activated integrin αIIbβ3, subsequently suppressing platelet spreading. In vivo study revealed that ZDPI inhibited carotid arterial thrombosis with limited bleeding and thrombocytopenia. A non-RGD peptide which targets the active conformation of integrin αIIbβ3, such as ZDPI, might be an excellent candidate or template to develop antithrombotics without significant bleeding and thrombocytopenia side effects.

ACS Style

Chuanbin Shen; Ming Liu; Huiwen Tian; Jiameng Li; Runjia Xu; James Mwangi; Qiumin Lu; Xue Hao; Ren Lai. Conformation-Specific Blockade of αIIbβ3 by a Non-RGD Peptide to Inhibit Platelet Activation without Causing Significant Bleeding and Thrombocytopenia. Thrombosis and Haemostasis 2020, 120, 1432 -1441.

AMA Style

Chuanbin Shen, Ming Liu, Huiwen Tian, Jiameng Li, Runjia Xu, James Mwangi, Qiumin Lu, Xue Hao, Ren Lai. Conformation-Specific Blockade of αIIbβ3 by a Non-RGD Peptide to Inhibit Platelet Activation without Causing Significant Bleeding and Thrombocytopenia. Thrombosis and Haemostasis. 2020; 120 (10):1432-1441.

Chicago/Turabian Style

Chuanbin Shen; Ming Liu; Huiwen Tian; Jiameng Li; Runjia Xu; James Mwangi; Qiumin Lu; Xue Hao; Ren Lai. 2020. "Conformation-Specific Blockade of αIIbβ3 by a Non-RGD Peptide to Inhibit Platelet Activation without Causing Significant Bleeding and Thrombocytopenia." Thrombosis and Haemostasis 120, no. 10: 1432-1441.

Journal article
Published: 06 February 2020 in Toxins
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Snake venoms contain components selected to immobilize prey. The venoms from Elapidae mainly contain neurotoxins, which are critical for rapid prey paralysis, while the venoms from Viperidae and Colubridae may contain fewer neurotoxins but are likely to induce circulatory disorders. Here, we show that the venoms from Protobothrops mucrosquamatus and Trimeresurus stejnegeri are comparable to those of Naja atra in prey immobilization. Further studies indicate that snake C-type lectin-like proteins (snaclecs), which are one of the main nonenzymatic components in viper venoms, are responsible for rapid prey immobilization. Snaclecs (mucetin and stejnulxin) from the venoms of P. mucrosquamatus and T. stejnegeri induce the aggregation of both mammalian platelets and avian thrombocytes, leading to acute cerebral ischemia, and reduced animal locomotor activity and exploration in the open field test. Viper venoms in the absence of snaclecs fail to aggregate platelets and thrombocytes, and thus show an attenuated ability to cause cerebral ischemia and immobilization of their prey. This work provides novel insights into the prey immobilization mechanism of Viperidae snakes and the understanding of viper envenomation-induced cerebral infarction.

ACS Style

Huiwen Tian; Ming Liu; Jiameng Li; Runjia Xu; Chengbo Long; Hao Li; James Mwangi; Qiumin Lu; Ren Lai; Chuanbin Shen; Li. Snake C-Type Lectins Potentially Contribute to the Prey Immobilization in Protobothrops mucrosquamatus and Trimeresurus stejnegeri Venoms. Toxins 2020, 12, 105 .

AMA Style

Huiwen Tian, Ming Liu, Jiameng Li, Runjia Xu, Chengbo Long, Hao Li, James Mwangi, Qiumin Lu, Ren Lai, Chuanbin Shen, Li. Snake C-Type Lectins Potentially Contribute to the Prey Immobilization in Protobothrops mucrosquamatus and Trimeresurus stejnegeri Venoms. Toxins. 2020; 12 (2):105.

Chicago/Turabian Style

Huiwen Tian; Ming Liu; Jiameng Li; Runjia Xu; Chengbo Long; Hao Li; James Mwangi; Qiumin Lu; Ren Lai; Chuanbin Shen; Li. 2020. "Snake C-Type Lectins Potentially Contribute to the Prey Immobilization in Protobothrops mucrosquamatus and Trimeresurus stejnegeri Venoms." Toxins 12, no. 2: 105.

Journal article
Published: 30 June 2019 in Toxins
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Antimalarial drug resistance is an enormous global threat. Recently, antimicrobial peptides (AMPs) are emerging as a new source of antimalarials. In this study, an AMP LZ1 derived from snake cathelicidin was identified with antimalarial activity. In the in vitro antiplasmodial assay, LZ1 showed strong suppression of blood stage Plasmodium falciparum (P. falciparum) with an IC50 value of 3.045 μM. In the in vivo antiplasmodial assay, LZ1 exerted a significant antimalarial activity against Plasmodium berghei (P. berghei) in a dose- and a time- dependent manner. In addition, LZ1 exhibited anti-inflammatory effects and attenuated liver-function impairment during P. berghei infection. Furthermore, by employing inhibitors against glycolysis and oxidative phosphorylation in erythrocytes, LZ1 specifically inhibited adenosine triphosphate (ATP) production in parasite-infected erythrocyte by selectively inhibiting the pyruvate kinase activity. In conclusion, the present study demonstrates that LZ1 is a potential candidate for novel antimalarials development.

ACS Style

Yaqun Fang; Xiaoqin He; Pengcheng Zhang; Chuanbin Shen; James Mwangi; Cheng Xu; Guoxiang Mo; Ren Lai; Zhiye Zhang. In Vitro and In Vivo Antimalarial Activity of LZ1, a Peptide Derived from Snake Cathelicidin. Toxins 2019, 11, 379 .

AMA Style

Yaqun Fang, Xiaoqin He, Pengcheng Zhang, Chuanbin Shen, James Mwangi, Cheng Xu, Guoxiang Mo, Ren Lai, Zhiye Zhang. In Vitro and In Vivo Antimalarial Activity of LZ1, a Peptide Derived from Snake Cathelicidin. Toxins. 2019; 11 (7):379.

Chicago/Turabian Style

Yaqun Fang; Xiaoqin He; Pengcheng Zhang; Chuanbin Shen; James Mwangi; Cheng Xu; Guoxiang Mo; Ren Lai; Zhiye Zhang. 2019. "In Vitro and In Vivo Antimalarial Activity of LZ1, a Peptide Derived from Snake Cathelicidin." Toxins 11, no. 7: 379.

Journal article
Published: 28 June 2019 in Chinese Journal of Natural Medicines
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Isoflavones are widely consumed by people around the world in the form of soy products, dietary supplements and drugs. Many isoflavones or related crude extracts have been reported to exert pain-relief activities, but the mechanism remains unclear. Voltage-gated sodium channels (VGSCs) play important roles in excitability of pain sensing neurons and many of them are important nociceptors. Here, we report that several isoflavones including 3′-methoxydaidzein (3MOD), genistein (GEN) and daidzein (DAI) show abilities to block VGSCs and thus to attenuate chemicals and heat induced acute pain or chronic constriction injury (CCI) induced pain hypersensitivity in mice. Especially, 3MOD shows strong analgesic potential without inducing addiction through inhibiting subtypes NaV1.7, NaV1.8 and NaV1.3 with the IC50 of 181 ± 14, 397 ± 26, and 505 ± 46 nmol·L−1, respectively, providing a promising compound or parent structure for the treatment of pain pathologies. This study reveals a pain-alleviating mechanism of dietary isoflavones and may provide a convenient avenue to alleviate pain.

ACS Style

Run-Jia Xu; Shuo-Han Fei; Lin-Yan Chen; Gan Wang; Ming Liu; Wen-Sheng Zhang; Xiu-Wen Yan; Ren Lai; Chuan-Bin Shen. 3′-Methoxydaidzein exerts analgesic activity by inhibiting voltage-gated sodium channels. Chinese Journal of Natural Medicines 2019, 17, 413 -423.

AMA Style

Run-Jia Xu, Shuo-Han Fei, Lin-Yan Chen, Gan Wang, Ming Liu, Wen-Sheng Zhang, Xiu-Wen Yan, Ren Lai, Chuan-Bin Shen. 3′-Methoxydaidzein exerts analgesic activity by inhibiting voltage-gated sodium channels. Chinese Journal of Natural Medicines. 2019; 17 (6):413-423.

Chicago/Turabian Style

Run-Jia Xu; Shuo-Han Fei; Lin-Yan Chen; Gan Wang; Ming Liu; Wen-Sheng Zhang; Xiu-Wen Yan; Ren Lai; Chuan-Bin Shen. 2019. "3′-Methoxydaidzein exerts analgesic activity by inhibiting voltage-gated sodium channels." Chinese Journal of Natural Medicines 17, no. 6: 413-423.

Journal article
Published: 05 March 2018 in Nature Immunology
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Pathogens have co-evolved with mosquitoes to optimize transmission to hosts. Mosquito salivary-gland extract is known to modulate host immune responses and facilitate pathogen transmission, but the underlying molecular mechanisms of this have remained unknown. In this study, we identified and characterized a prominent 15-kilodalton protein, LTRIN, obtained from the salivary glands of the mosquito Aedes aegypti. LTRIN expression was upregulated in blood-fed mosquitoes, and LTRIN facilitated the transmission of Zika virus (ZIKV) and exacerbated its pathogenicity by interfering with signaling through the lymphotoxin-β receptor (LTβR). Mechanically, LTRIN bound to LTβR and ‘preferentially’ inhibited signaling via the transcription factor NF-κB and the production of inflammatory cytokines by interfering with the dimerization of LTβR during infection with ZIKV. Furthermore, treatment with antibody to LTRIN inhibited mosquito-mediated infection with ZIKV, and abolishing LTβR potentiated the infectivity of ZIKV both in vitro and in vivo. This study provides deeper insight into the transmission of mosquito-borne diseases in nature and supports the therapeutic potential of inhibiting the action of LTRIN to disrupt ZIKV transmission.

ACS Style

Lin Jin; Xiaomin Guo; Chuanbin Shen; Xuexue Hao; Peng Sun; Pengpeng Li; Tao Xu; Chunmiao Hu; Ombati Rose; Hongning Zhou; Mingdong Yang; Cheng-Feng Qin; Jingya Guo; Hua Peng; Mingzhao Zhu; Gong Cheng; Xiaopeng Qi; Ren Lai. Salivary factor LTRIN from Aedes aegypti facilitates the transmission of Zika virus by interfering with the lymphotoxin-β receptor. Nature Immunology 2018, 19, 342 -353.

AMA Style

Lin Jin, Xiaomin Guo, Chuanbin Shen, Xuexue Hao, Peng Sun, Pengpeng Li, Tao Xu, Chunmiao Hu, Ombati Rose, Hongning Zhou, Mingdong Yang, Cheng-Feng Qin, Jingya Guo, Hua Peng, Mingzhao Zhu, Gong Cheng, Xiaopeng Qi, Ren Lai. Salivary factor LTRIN from Aedes aegypti facilitates the transmission of Zika virus by interfering with the lymphotoxin-β receptor. Nature Immunology. 2018; 19 (4):342-353.

Chicago/Turabian Style

Lin Jin; Xiaomin Guo; Chuanbin Shen; Xuexue Hao; Peng Sun; Pengpeng Li; Tao Xu; Chunmiao Hu; Ombati Rose; Hongning Zhou; Mingdong Yang; Cheng-Feng Qin; Jingya Guo; Hua Peng; Mingzhao Zhu; Gong Cheng; Xiaopeng Qi; Ren Lai. 2018. "Salivary factor LTRIN from Aedes aegypti facilitates the transmission of Zika virus by interfering with the lymphotoxin-β receptor." Nature Immunology 19, no. 4: 342-353.

Journal article
Published: 19 October 2016 in EBioMedicine
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Psoriasis is histologically characterized by keratinocytes (KC) hyperproliferation, inflammation, and increased angiogenesis, but the pathological factor responsible for these symptoms is unknown. Here, a neuroendocrine peptide (prokineticin 2, PK2), is highly expressed in human and mouse psoriatic skins but no significant change in other autoimmune diseases, suggesting that PK2 is a psoriasis-specific factor. Bacterial products significantly up-regulated PK2, implying that infection induces PK2 over-expression. PK2 promoted KC and macrophage to produce interleukin-1 (IL-1), the central player of inflammation and psoriasis, which acts on adjacent fibroblast to induce inflammatory cascades and KC hyperproliferation. IL-1 feeds back on macrophages to induce PK2 production to perpetuate PK2-IL-1 positive feedback loop. PK2 also promoted angiogenesis, another psoriatic symptom. In mouse models, PK2 over-expression aggravated psoriasis while its knock-down inhibited pathological development. The results indicate that PK2 over-production perpetuates psoriatic symptoms by creating PK-2-IL-1 vicious loop. PK2 is a central player in psoriasis and a promising psoriasis-specific target.

ACS Style

Xiaoqin He; Chuanbin Shen; Qiumin Lu; Jiong Li; Yuquan Wei; Li He; Ruizhen Bai; Jie Zheng; Ning Luan; Zhiye Zhang; Mingqiang Rong; Ren Lai. Prokineticin 2 Plays a Pivotal Role in Psoriasis. EBioMedicine 2016, 13, 248 -261.

AMA Style

Xiaoqin He, Chuanbin Shen, Qiumin Lu, Jiong Li, Yuquan Wei, Li He, Ruizhen Bai, Jie Zheng, Ning Luan, Zhiye Zhang, Mingqiang Rong, Ren Lai. Prokineticin 2 Plays a Pivotal Role in Psoriasis. EBioMedicine. 2016; 13 ():248-261.

Chicago/Turabian Style

Xiaoqin He; Chuanbin Shen; Qiumin Lu; Jiong Li; Yuquan Wei; Li He; Ruizhen Bai; Jie Zheng; Ning Luan; Zhiye Zhang; Mingqiang Rong; Ren Lai. 2016. "Prokineticin 2 Plays a Pivotal Role in Psoriasis." EBioMedicine 13, no. : 248-261.

Journal article
Published: 08 December 2015 in Immunity
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Summary Atherosclerosis is a chronic inflammatory disease of arterial wall. Mitochondrial DNA (mtDNA) and human antimicrobial peptide LL-37 (Cramp in mice) are involved in atherosclerosis. Recently, mtDNA has been found to escape from autophagy and cause inflammation. Normally, mtDNA as an inflammatogenic factor cannot escape from autophagy and degradation by DNase II. In this study, we found elevated amounts of LL37-mtDNA complex in atherosclerotic plasma and plaques. The complex was resistant to DNase II degradation and escaped from autophagic recognition, leading to activation of Toll-like receptor 9 (TLR9)-mediated inflammatory responses. Mouse model studies indicated that Cramp-mtDNA complex aggravated atherosclerotic lesion formation in apolipoprotein E-deficient mice and antibody treatment against the complex alleviated the lesion. These findings suggest that the LL-37-mtDNA complex acts as a key mediator of atherosclerosis formation, and thus represents a promising therapeutic target.

ACS Style

Zhiye Zhang; Ping Meng; Yajun Han; Chuanbin Shen; Bowen Li; Abdul Hakim; Xuguang Zhang; Qiumin Lu; Mingqiang Rong; Ren Lai. Mitochondrial DNA-LL-37 Complex Promotes Atherosclerosis by Escaping from Autophagic Recognition. Immunity 2015, 43, 1137 -1147.

AMA Style

Zhiye Zhang, Ping Meng, Yajun Han, Chuanbin Shen, Bowen Li, Abdul Hakim, Xuguang Zhang, Qiumin Lu, Mingqiang Rong, Ren Lai. Mitochondrial DNA-LL-37 Complex Promotes Atherosclerosis by Escaping from Autophagic Recognition. Immunity. 2015; 43 (6):1137-1147.

Chicago/Turabian Style

Zhiye Zhang; Ping Meng; Yajun Han; Chuanbin Shen; Bowen Li; Abdul Hakim; Xuguang Zhang; Qiumin Lu; Mingqiang Rong; Ren Lai. 2015. "Mitochondrial DNA-LL-37 Complex Promotes Atherosclerosis by Escaping from Autophagic Recognition." Immunity 43, no. 6: 1137-1147.

Journal article
Published: 01 September 2014 in The International Journal of Biochemistry & Cell Biology
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Vasotab TY is a KGD (Lys-Gly-Asp)-containing peptide identified from salivary glands of the horsefly of Tabanus yao. We have previously reported that vasotab TY showed a strong vasodilator activity. In the present study, vasotab TY was found to inhibit platelet aggregation effectively. It completely inhibited platelet aggregation induced by adenosine diphosphate (ADP) at the concentration of 9.6μg/ml. Vasotab TY significantly reduced thrombus weight in rat arteriovenous shunt model and inhibited thrombosis in carrageenan-induced mouse tail thrombosis model in vivo. Vasotab TY competitively bound to glycoprotein IIb/IIIa (GPIIb/IIIa) with eptifibatide, a well-known KGD-containing cyclic heptapeptide containing high specificity and high affinity for GPIIb/IIIa, suggesting that it is an antagonist of the fibrinogen receptor GPIIb/IIIa on the surface of platelet. The KGD motif in vasotab TY may facilitate the binding of it to GPIIb/IIIa. Vasotab TY showed a half-life of more than 1h in vivo. It showed little side effects including little bleeding, no hemolytic activity on human blood red cells and no cytotoxicity on human keratinocyte and THP-1 cells. Combined its vasodilator and platelet inhibitory functions, vasotab TY might be an excellent candidate for the development of clinical anti-thrombosis medicines.

ACS Style

Zhiye Zhang; Lan Gao; Chuanbin Shen; Mingqiang Rong; Xiuwen Yan; Ren Lai. A potent anti-thrombosis peptide (vasotab TY) from horsefly salivary glands. The International Journal of Biochemistry & Cell Biology 2014, 54, 83 -88.

AMA Style

Zhiye Zhang, Lan Gao, Chuanbin Shen, Mingqiang Rong, Xiuwen Yan, Ren Lai. A potent anti-thrombosis peptide (vasotab TY) from horsefly salivary glands. The International Journal of Biochemistry & Cell Biology. 2014; 54 ():83-88.

Chicago/Turabian Style

Zhiye Zhang; Lan Gao; Chuanbin Shen; Mingqiang Rong; Xiuwen Yan; Ren Lai. 2014. "A potent anti-thrombosis peptide (vasotab TY) from horsefly salivary glands." The International Journal of Biochemistry & Cell Biology 54, no. : 83-88.

Journal article
Published: 27 May 2014 in The FASEB Journal
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Although it is well known that wound healing proceeds incredibly quickly in urodele amphibians, such as newts and salamanders, little is known about skin-wound healing, and no bioactive/effector substance that contributes to wound healing has been identified from these animals. As a step toward understanding salamander wound healing and skin regeneration, a potential wound-healing-promoting peptide (tylotoin; KCVRQNNKRVCK) was identified from salamander skin of Tylototriton verrucosus. It shows comparable wound-healing-promoting ability (EC50=11.14 μg/ml) with epidermal growth factor (EGF; NSDSECPLSHDGYCLHDGVCMYIEALDKYACNCVVGYIGERCQYRDLKWWELR) in a murine model of full-thickness dermal wound. Tylotoin directly enhances the motility and proliferation of keratinocytes, vascular endothelial cells, and fibroblasts, resulting in accelerated reepithelialization and granulation tissue formation in the wound site. Tylotoin also promotes the release of transforming growth factor β1 (TGF-β1) and interleukin 6 (IL-6), which are essential in the wound healing response. Gene-encoded tylotoin secreted in salamander skin is possibly an effector molecule for skin wound healing. This study may facilitate understanding of the cellular and molecular events that underlie quick wound healing in salamanders.—Mu, L., Tang, J., Liu, H., Shen, C., Rong, M., Zhang, Z., Lai, R. A potential wound-healing-promoting peptide from salamander skin.

ACS Style

Lixian Mu; Jing Tang; Han Liu; Chuanbin Shen; Mingqiang Rong; Zhiye Zhang; Ren Lai. A potential wound‐healing‐promoting peptide from salamander skin. The FASEB Journal 2014, 28, 3919 -3929.

AMA Style

Lixian Mu, Jing Tang, Han Liu, Chuanbin Shen, Mingqiang Rong, Zhiye Zhang, Ren Lai. A potential wound‐healing‐promoting peptide from salamander skin. The FASEB Journal. 2014; 28 (9):3919-3929.

Chicago/Turabian Style

Lixian Mu; Jing Tang; Han Liu; Chuanbin Shen; Mingqiang Rong; Zhiye Zhang; Ren Lai. 2014. "A potential wound‐healing‐promoting peptide from salamander skin." The FASEB Journal 28, no. 9: 3919-3929.

Journal article
Published: 01 April 2014 in The International Journal of Biochemistry & Cell Biology
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Cutaneous wound healing is a dynamic, complex, and well-organized process that requires the orchestration of many different cell types and cellular processes. Transforming growth factor β1 is an important factor that plays a key role during wound healing. Amphibian skin has been proven to possess excellent wound healing ability, whilst no bioactive substrate related to it has ever been identified. Here, a potential wound healing-promoting peptide (AH90, ATAWDFGPHGLLPIRPIRIRPLCG) was identified from the frog skin of Odorrana grahami. It showed potential wound healing-promoting activity in a murine model with full thickness dermal wound. AH90 promoted release of transforming growth factor β1 through activation of nuclear factor-κB and c-Jun NH2-terminal kinase mitogen-activated protein kinases signaling pathways, while inhibitors of nuclear factor-κB and c-Jun NH2-terminal kinase inhibited the process. In addition, the effects of AH90 on Smads family proteins, key regulators in transforming growth factor β1 signaling pathways, could also be inhibited by transforming growth factor β1 antibody. Altogether, this indicated that AH90 promoted wound healing by inducing the release of transforming growth factor β1. This current study may facilitate the understanding of effective factors involved in the wound repair of amphibians and the underlying mechanisms as well. Considering its favorable traits as a small peptide that greatly promoting generation of endogenous wound healing agents (transforming growth factor β1) without mitogenic effects, AH90 might be an excellent template for the future development of novel wound-healing agents.

ACS Style

Han Liu; Lixian Mu; Jing Tang; Chuanbin Shen; Chen Gao; Mingqiang Rong; Zhiye Zhang; Jie Liu; Xiaoyang Wu; Haining Yu; Ren Lai. A potential wound healing-promoting peptide from frog skin. The International Journal of Biochemistry & Cell Biology 2014, 49, 32 -41.

AMA Style

Han Liu, Lixian Mu, Jing Tang, Chuanbin Shen, Chen Gao, Mingqiang Rong, Zhiye Zhang, Jie Liu, Xiaoyang Wu, Haining Yu, Ren Lai. A potential wound healing-promoting peptide from frog skin. The International Journal of Biochemistry & Cell Biology. 2014; 49 ():32-41.

Chicago/Turabian Style

Han Liu; Lixian Mu; Jing Tang; Chuanbin Shen; Chen Gao; Mingqiang Rong; Zhiye Zhang; Jie Liu; Xiaoyang Wu; Haining Yu; Ren Lai. 2014. "A potential wound healing-promoting peptide from frog skin." The International Journal of Biochemistry & Cell Biology 49, no. : 32-41.

Journal article
Published: 12 March 2014 in Biochimie
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26RFa is one of neuroendocrine peptide groups in the RFamide peptide family containing conserved Arg-Phe/Tyr-NH2 motif at their C-terminus. They exert multiple biological functions in vertebrates. A novel 26RFa peptide (TC26RFa) with unique structure is identified from the tree shrew of Tupaia belangeri chinensis in the present study. In structure, different from other 26RFa peptides containing conserved Phe-Arg-Phe-NH2 motif at their C-terminus, there is a Phe-Arg-Tyr-NH2 C-terminus in TC26RFa. It has been found that TC26RFa of intraperitoneal injection exerts strong analgesic activities in several mice models including acetic acid-induced abdominal writhing, formalin-induced paw licking, and thermal pain-induced tail withdrawal. It shows comparable analgesic ability with morphine. In addition, this peptide has been found to inhibit inflammatory factor secretion (including tumor necrosis factor-α, interleukin-6, and interleukin-1β) induced by lipopolysaccharides (LPS). Furthermore, it stimulates secretion of the anti-inflammatory factor, interleukin-10. In addition to the identification of a novel 26RFa peptide from tree shrew, a new type of function (anti-inflammation) involved in 26RFa peptide is discovered.

ACS Style

Yuqin Zhu; Zilei Duan; Guoxiang Mo; Chuanbin Shen; Longbao Lv; Wenlin Chen; Ren Lai. A novel 26RFa peptide containing both analgesic and anti-inflammatory functions from Chinese tree shrew. Biochimie 2014, 102, 112 -116.

AMA Style

Yuqin Zhu, Zilei Duan, Guoxiang Mo, Chuanbin Shen, Longbao Lv, Wenlin Chen, Ren Lai. A novel 26RFa peptide containing both analgesic and anti-inflammatory functions from Chinese tree shrew. Biochimie. 2014; 102 ():112-116.

Chicago/Turabian Style

Yuqin Zhu; Zilei Duan; Guoxiang Mo; Chuanbin Shen; Longbao Lv; Wenlin Chen; Ren Lai. 2014. "A novel 26RFa peptide containing both analgesic and anti-inflammatory functions from Chinese tree shrew." Biochimie 102, no. : 112-116.

Research article
Published: 30 December 2013 in PLOS ONE
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Antimicrobial peptides have been widely identified from amphibian skins except salamanders. A novel antimicrobial peptide (CFBD) was isolated and characterized from skin secretions of the salamander, Cynops fudingensis. The cDNA encoding CFBD precursor was cloned from the skin cDNA library of C. fudingensis. The precursor was composed of three domains: signal peptide of 17 residues, mature peptide of 41 residues and intervening propeptide of 3 residues. There are six cysteines in the sequence of mature CFBD peptide, which possibly form three disulfide-bridges. CFBD showed antimicrobial activities against Staphylococcus aureus, Bacillus subtilis, Candida albicans and Escherichia coli. This peptide could be classified into family of β-defensin based on its seqeuence similarity with β-defensins from other vertebrates. Evolution analysis indicated that CFBD was close to fish β-defensin. As far as we know, CFBD is the first β-defensin antimicrobial peptide from salamanders.

ACS Style

Ping Meng; Shilong Yang; Chuanbin Shen; Ke Jiang; Mingqiang Rong; Ren Lai. The First Salamander Defensin Antimicrobial Peptide. PLOS ONE 2013, 8, e83044 .

AMA Style

Ping Meng, Shilong Yang, Chuanbin Shen, Ke Jiang, Mingqiang Rong, Ren Lai. The First Salamander Defensin Antimicrobial Peptide. PLOS ONE. 2013; 8 (12):e83044.

Chicago/Turabian Style

Ping Meng; Shilong Yang; Chuanbin Shen; Ke Jiang; Mingqiang Rong; Ren Lai. 2013. "The First Salamander Defensin Antimicrobial Peptide." PLOS ONE 8, no. 12: e83044.