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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.
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 StyleChengbo 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 StyleChengbo 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.
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.
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 StyleYaqun 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 StyleYaqun 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.
It was recently discovered that Ssm Spooky Toxin (SsTx) with 53 residues serves as a key killer factor in red-headed centipede’s venom arsenal, due to its potent blockage of the widely expressed KCNQ channels to simultaneously and efficiently disrupt cardiovascular, respiratory, muscular, and nervous systems, suggesting that SsTx is a basic compound for centipedes’ defense and predation. Here, we show that SsTx also inhibits KV1.3 channel, which would amplify the broad-spectrum disruptive effect of blocking KV7 channels. Interestingly, residue R12 in SsTx extends into the selectivity filter to block KV7.4, however, residue K11 in SsTx replaces this ploy when toxin binds on KV1.3. Both SsTx and its mutant SsTx_R12A inhibit cytokines production in T cells without affecting the level of KV1.3 expression. The results further suggest that SsTx is a key molecule for defense and predation in the centipedes’ venoms and it evolves efficient strategy to disturb multiple physiological targets.
Canwei Du; Jiameng Li; Zicheng Shao; James Mwangi; Runjia Xu; Huiwen Tian; Guoxiang Mo; Ren Lai; Shilong Yang. Centipede KCNQ Inhibitor SsTx Also Targets KV1.3. Toxins 2019, 11, 76 .
AMA StyleCanwei Du, Jiameng Li, Zicheng Shao, James Mwangi, Runjia Xu, Huiwen Tian, Guoxiang Mo, Ren Lai, Shilong Yang. Centipede KCNQ Inhibitor SsTx Also Targets KV1.3. Toxins. 2019; 11 (2):76.
Chicago/Turabian StyleCanwei Du; Jiameng Li; Zicheng Shao; James Mwangi; Runjia Xu; Huiwen Tian; Guoxiang Mo; Ren Lai; Shilong Yang. 2019. "Centipede KCNQ Inhibitor SsTx Also Targets KV1.3." Toxins 11, no. 2: 76.
Antistasin, first identified as a potent inhibitor of the blood coagulation factor Xa, is a novel family of serine protease inhibitors. In this study, we purified a novel antistasin-type inhibitor from leech Poecilobdella manillensis called poecistasin. Amino acid sequencing of this 48-amino-acid protein revealed that poecistasin was an antistasin-type inhibitor known to consist of only one domain. Poecistasin inhibited factor XIIa, kallikrein, trypsin, and elastase, but had no inhibitory effect on factor Xa and thrombin. Poecistasin showed anticoagulant activities. It prolonged the activated partial thromboplastin time and inhibited FeCl3-induced carotid artery thrombus formation, implying its potent function in helping Poecilobdella manillensis to take a blood meal from the host by inhibiting coagulation. Poecistasin also suppressed ischemic stroke symptoms in transient middle cerebral artery occlusion mice model. Our results suggest that poecistasin from the leech Poecilobdella manillensis plays a crucial role in blood-sucking and may be an excellent candidate for the development of clinical anti-thrombosis and anti-ischemic stroke medicines.
Xiaopeng Tang; Mengrou Chen; Zilei Duan; James Mwangi; Pengpeng Li; Ren Lai. Isolation and Characterization of Poecistasin, an Anti-Thrombotic Antistasin-Type Serine Protease Inhibitor from Leech Poecilobdella manillensis. Toxins 2018, 10, 429 .
AMA StyleXiaopeng Tang, Mengrou Chen, Zilei Duan, James Mwangi, Pengpeng Li, Ren Lai. Isolation and Characterization of Poecistasin, an Anti-Thrombotic Antistasin-Type Serine Protease Inhibitor from Leech Poecilobdella manillensis. Toxins. 2018; 10 (11):429.
Chicago/Turabian StyleXiaopeng Tang; Mengrou Chen; Zilei Duan; James Mwangi; Pengpeng Li; Ren Lai. 2018. "Isolation and Characterization of Poecistasin, an Anti-Thrombotic Antistasin-Type Serine Protease Inhibitor from Leech Poecilobdella manillensis." Toxins 10, no. 11: 429.