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Thermally processed Buthus martensii Karsch scorpions are a traditional Chinese medical material for treating various diseases. However, their pharmacological foundation remains unclear. Here, a new degraded peptide of scorpion toxin was identified in Chinese scorpion medicinal material by proteomics. It was named BmK86-P1 and has six conserved cysteine residues. Homology modeling and circular dichroism spectra experiments revealed that BmK86-P1 not only contained representative disulfide bond-stabilized α-helical and β-sheet motifs but also showed remarkable stability at test temperatures from 20–95 °C. Electrophysiology experiments indicated that BmK86-P1 was a highly potent and selective inhibitor of the hKv1.2 channel with IC50 values of 28.5 ± 6.3 nM. Structural and functional dissection revealed that two residues of BmK86-P1 (i.e., Lys19 and Ile21) were the key residues that interacted with the hKv1.2 channel. In addition, channel chimeras and mutagenesis experiments revealed that three amino acids (i.e., Gln357, Val381 and Thr383) of the hKv1.2 channel were responsible for BmK86-P1 selectivity. This research uncovered a new bioactive peptide from traditional Chinese scorpion medicinal material that has desirable thermostability and Kv1.2 channel-specific activity, which strongly suggests that thermally processed scorpions are novel peptide resources for new drug discovery for the Kv1.2 channel-related ataxia and epilepsy diseases.
Chenhu Qin; Xuhua Yang; Zheng Zuo; Liuting Yang; Fan Yang; Zhijian Cao; Zongyun Chen; Yingliang Wu. BmK86-P1, a New Degradation Peptide with Desirable Thermostability and Kv1.2 Channel-Specific Activity from Traditional Chinese Scorpion Medicinal Material. Toxins 2021, 13, 610 .
AMA StyleChenhu Qin, Xuhua Yang, Zheng Zuo, Liuting Yang, Fan Yang, Zhijian Cao, Zongyun Chen, Yingliang Wu. BmK86-P1, a New Degradation Peptide with Desirable Thermostability and Kv1.2 Channel-Specific Activity from Traditional Chinese Scorpion Medicinal Material. Toxins. 2021; 13 (9):610.
Chicago/Turabian StyleChenhu Qin; Xuhua Yang; Zheng Zuo; Liuting Yang; Fan Yang; Zhijian Cao; Zongyun Chen; Yingliang Wu. 2021. "BmK86-P1, a New Degradation Peptide with Desirable Thermostability and Kv1.2 Channel-Specific Activity from Traditional Chinese Scorpion Medicinal Material." Toxins 13, no. 9: 610.
Carbapenem-resistant Acinetobacter baumannii (CRAB) is becoming a troublesome issue worldwide, and anti-CRAB drug research and development is urgently needed. To identify new anti-CRAB drug leads, we investigated seven scorpion venom-derived α-helical peptides that differ in their sequence composition and length. Three peptides, Hp1404, ctriporin and Im5, showed antimicrobial activities against Acinetobacter baumannii. Further antimicrobial assays revealed that Hp1404 exhibited the best cell selectivity with high anti-CRAB and low hemolytic activities. Fluorescence assays demonstrated that Hp1404 can induce dose-dependent disruptions of the bacterial cell membrane, implying a membrane-lytic mode of action. Taken together, our work sheds light on the potential of the scorpion venom-derived peptide Hp1404 for the development of novel antimicrobial agents against CRAB infections.
Xudong Luo; Xiangdong Ye; Li Ding; Wen Zhu; Zhiwen Zhao; Dan Luo; Na Liu; Luyue Sun; Zongyun Chen. Identification of the scorpion venom-derived antimicrobial peptide Hp1404 as a new antimicrobial agent against carbapenem-resistant Acinetobacter baumannii. Microbial Pathogenesis 2021, 157, 104960 .
AMA StyleXudong Luo, Xiangdong Ye, Li Ding, Wen Zhu, Zhiwen Zhao, Dan Luo, Na Liu, Luyue Sun, Zongyun Chen. Identification of the scorpion venom-derived antimicrobial peptide Hp1404 as a new antimicrobial agent against carbapenem-resistant Acinetobacter baumannii. Microbial Pathogenesis. 2021; 157 ():104960.
Chicago/Turabian StyleXudong Luo; Xiangdong Ye; Li Ding; Wen Zhu; Zhiwen Zhao; Dan Luo; Na Liu; Luyue Sun; Zongyun Chen. 2021. "Identification of the scorpion venom-derived antimicrobial peptide Hp1404 as a new antimicrobial agent against carbapenem-resistant Acinetobacter baumannii." Microbial Pathogenesis 157, no. : 104960.
Scorpion venoms are rich resources of antimicrobial peptides (AMPs). While the short-chain noncysteine-containing AMPs have attracted much attention as templates for drug development, the antimicrobial potential of long-chain noncysteine-containing AMPs has been largely overlooked. Here, by using the online HeliQuest server, we designed and analyzed a series of 14-residue fragments of Smp43, a 43-residue long-chain noncysteine-containing AMP identified from the venom of Scorpio maurus palmatus. We found that Smp43(1-14) shows high antimicrobial activity against both Gram-positive and Gram-negative bacteria and is nontoxic to mammalian cells at the antimicrobial dosage. Sequence alignments showed that the designed Smp43(1-14) displays a unique primary structure that is different from other natural short-chain noncysteine-containing AMPs from scorpions, such as Uy17, Uy192 and IsCT. Moreover, the peptide Smp43(1-14) caused concentration-dependent fluorescence increases in the bacteria for all of the tested dyes, propidium iodide, SYTOXTM Green and DiSC3-5, suggesting that the peptide may kill the bacteria through the formation of pore structures in the plasma membrane. Taken together, our work sheds light on a new avenue for the design of novel short-chain noncysteine-containing AMPs and provides a good peptide template with a unique sequence for the development of novel drugs for use against bacterial infectious diseases.
Xudong Luo; Li Ding; Xiangdong Ye; Wen Zhu; Kaiyue Zhang; Fangyan Li; Huiwen Jiang; Zhiwen Zhao; Zongyun Chen. An Smp43-Derived Short-Chain α-Helical Peptide Displays a Unique Sequence and Possesses Antimicrobial Activity against Both Gram-Positive and Gram-Negative Bacteria. Toxins 2021, 13, 343 .
AMA StyleXudong Luo, Li Ding, Xiangdong Ye, Wen Zhu, Kaiyue Zhang, Fangyan Li, Huiwen Jiang, Zhiwen Zhao, Zongyun Chen. An Smp43-Derived Short-Chain α-Helical Peptide Displays a Unique Sequence and Possesses Antimicrobial Activity against Both Gram-Positive and Gram-Negative Bacteria. Toxins. 2021; 13 (5):343.
Chicago/Turabian StyleXudong Luo; Li Ding; Xiangdong Ye; Wen Zhu; Kaiyue Zhang; Fangyan Li; Huiwen Jiang; Zhiwen Zhao; Zongyun Chen. 2021. "An Smp43-Derived Short-Chain α-Helical Peptide Displays a Unique Sequence and Possesses Antimicrobial Activity against Both Gram-Positive and Gram-Negative Bacteria." Toxins 13, no. 5: 343.
Methotrexate (MTX) has been widely used for the treatment of many types of autoimmune diseases, such as rheumatoid arthritis, psoriasis and dermatomyositis. However, its pharmacological mechanism is still unclear completely. In this study, we found that MTX is a potent and selective inhibitor of the Kv1.3 channel, a class of potassium channels highly associated with autoimmune diseases. Electrophysiological experiments showed that MTX inhibited human Kv1.3 channel with an IC50 of 41.5 ± 24.9 nM, and 1 μM MTX inhibited 32.6 ± 1.3% and 25.6 ± 2.2% of human Kv1.1 and Kv1.2 channel currents, respectively. These data implied the unique selectivity of MTX towards the Kv1.3 channel. Excitingly, using channel activation and chimeric experiments, we found that MTX bound to the outer pore region of Kv1.3 channel. Mutagenesis experiments in the Kv.3 channel extracellular pore region further showed that the Dsp371, Thr373 and His399 residues of outer pore region of Kv1.3 channel played important roles in MTX inhibiting activities. In conclusion, MTX inhibited Kv1.3 channel by targeting extracellular pore region, which is different form all the report small molecules, such as PAP-1 and 4-AP, but similar with many natural animal toxin peptides, such as ChTX, ShK and BmKTX. To the best of our knowledge, MTX is the first small molecular scaffold targeting the Kv1.3 channel extracellular pore region, suggesting its potential applications for designing novel Kv1.3 lead drugs and treating Kv1.3 channel-associated autoimmune diseases.
Zili Xie; Yonghui Zhao; Weishan Yang; Wenxin Li; Yingliang Wu; Zongyun Chen. Methotrexate, a small molecular scaffold targeting Kv1.3 channel extracellular pore region. Biochemical and Biophysical Research Communications 2020, 532, 265 -270.
AMA StyleZili Xie, Yonghui Zhao, Weishan Yang, Wenxin Li, Yingliang Wu, Zongyun Chen. Methotrexate, a small molecular scaffold targeting Kv1.3 channel extracellular pore region. Biochemical and Biophysical Research Communications. 2020; 532 (2):265-270.
Chicago/Turabian StyleZili Xie; Yonghui Zhao; Weishan Yang; Wenxin Li; Yingliang Wu; Zongyun Chen. 2020. "Methotrexate, a small molecular scaffold targeting Kv1.3 channel extracellular pore region." Biochemical and Biophysical Research Communications 532, no. 2: 265-270.
Only a few work have been done for peptides from non-venom gland tissues of venomous animals. Here, with the help of the whole body transcriptomic and the hemolymph proteomic data of the Chinese scorpion Buthus martensii Karsch, we identified the first Ascaris-type peptide BmHDP from scorpion hemolymph. The precursor of BmHDP has 80 residues, including a 16 residue signal peptide and a 64 residue mature peptide. The mature peptide has 10 conserved cysteines and adopts a conserved Ascaris-type fold. Using combined inclusion body refolding and biochemical identification strategies, recombinant BmHDP was obtained successfully. Protease inhibitory assays showed that BmHDP inhibited chymotrypsin apparently at a concentration of 8 nM. Patch-clamp experiments showed that BmHDP inhibited the Kv1.3 potassium channel apparently at a concentration of 1000 nM. Coagulation experiment assays showed that BmHDP inhibited intrinsic coagulation pathway apparently at a concentration of 500 nM. To the best of our knowledge, BmHDP is the first Ascaris-type peptide from scorpion hemolymph. Our work highlighted a functional link between scorpion non-venom gland peptides and venom gland toxin peptides, and suggested that scorpion hemolymph might be a new source of bioactive peptides.
Wen Zhu; Huanhuan Gao; Xudong Luo; Xiangdong Ye; Li Ding; Jinbo Hao; Zhan Shu; Shan Li; Jian Li; Zongyun Chen. Cloning and identification of a new multifunctional Ascaris-type peptide from the hemolymph of Buthus martensii Karsch. Toxicon 2020, 184, 167 -174.
AMA StyleWen Zhu, Huanhuan Gao, Xudong Luo, Xiangdong Ye, Li Ding, Jinbo Hao, Zhan Shu, Shan Li, Jian Li, Zongyun Chen. Cloning and identification of a new multifunctional Ascaris-type peptide from the hemolymph of Buthus martensii Karsch. Toxicon. 2020; 184 ():167-174.
Chicago/Turabian StyleWen Zhu; Huanhuan Gao; Xudong Luo; Xiangdong Ye; Li Ding; Jinbo Hao; Zhan Shu; Shan Li; Jian Li; Zongyun Chen. 2020. "Cloning and identification of a new multifunctional Ascaris-type peptide from the hemolymph of Buthus martensii Karsch." Toxicon 184, no. : 167-174.
Scorpion toxins are well-known as the largest potassium channel peptide blocker family. They have been successfully proven to be valuable molecular probes for structural research on diverse potassium channels. The potassium channel pore region, including the turret and filter regions, is the binding interface for scorpion toxins, and structural features from different potassium channels have been identified using different scorpion toxins. According to the spatial orientation of channel turrets with differential sequence lengths and identities, conformational changes and molecular surface properties, the potassium channel turrets can be divided into the following three states: open state with less hindering effects on toxin binding, half-open state or half-closed state with certain effects on toxin binding, and closed state with remarkable effects on toxin binding. In this review, we summarized the diverse structural features of potassium channels explored using scorpion toxin tools and discuss future work in the field of scorpion toxin-potassium channel interactions.
Yonghui Zhao; Zongyun Chen; Zhijian Cao; Wenxin Li; Yingliang Wu. Diverse Structural Features of Potassium Channels Characterized by Scorpion Toxins as Molecular Probes. Molecules 2019, 24, 2045 .
AMA StyleYonghui Zhao, Zongyun Chen, Zhijian Cao, Wenxin Li, Yingliang Wu. Diverse Structural Features of Potassium Channels Characterized by Scorpion Toxins as Molecular Probes. Molecules. 2019; 24 (11):2045.
Chicago/Turabian StyleYonghui Zhao; Zongyun Chen; Zhijian Cao; Wenxin Li; Yingliang Wu. 2019. "Diverse Structural Features of Potassium Channels Characterized by Scorpion Toxins as Molecular Probes." Molecules 24, no. 11: 2045.
Fungus defensin is a kind of important natural peptide resource, such as plectasin from the soil fungus Pseudoplectania nigrella with potential application in the antimicrobial peptide lead drug discovery. Here, a fungus defensin named Bldesin with Kv1.3 channel and serine protease inhibitory activities was first explored. By GST‐Bldesin fusion expression and enterokinase cleaving strategy, recombinant Bldesin was obtained successfully. Antimicrobial assays showed that Bldesin had potent activity against Gram‐positive Staphylococcus aureus, but had no effect on Gram‐negative Escherichia coli. Electrophysiological experiments showed that Bldesin had Kv1.3 channel inhibitory activity. Serine protease inhibitory associated experiments showed that Bldesin had unique chymotrypsin protease inhibitory, elastase protease inhibitory, and serine protease‐associated coagulation inhibitory activities. To the best of our knowledge, Bldesin is the first functionally characterized pathogenic fungus defensin with Kv1.3 channel and chymotrypsin inhibitory activities and highlighted novel pharmacological effects of fungus‐derived defensin peptides.
Xudong Luo; Wen Zhu; Li Ding; Xiangdong Ye; Huanhuan Gao; Xuejiao Tai; Zheng Wu; Yi Qian; Xuzhi Ruan; Jian Li; Shan Li; Zongyun Chen. Bldesin, the first functionally characterized pathogenic fungus defensin with Kv1.3 channel and chymotrypsin inhibitory activities. Journal of Biochemical and Molecular Toxicology 2018, 33, e22244 .
AMA StyleXudong Luo, Wen Zhu, Li Ding, Xiangdong Ye, Huanhuan Gao, Xuejiao Tai, Zheng Wu, Yi Qian, Xuzhi Ruan, Jian Li, Shan Li, Zongyun Chen. Bldesin, the first functionally characterized pathogenic fungus defensin with Kv1.3 channel and chymotrypsin inhibitory activities. Journal of Biochemical and Molecular Toxicology. 2018; 33 (2):e22244.
Chicago/Turabian StyleXudong Luo; Wen Zhu; Li Ding; Xiangdong Ye; Huanhuan Gao; Xuejiao Tai; Zheng Wu; Yi Qian; Xuzhi Ruan; Jian Li; Shan Li; Zongyun Chen. 2018. "Bldesin, the first functionally characterized pathogenic fungus defensin with Kv1.3 channel and chymotrypsin inhibitory activities." Journal of Biochemical and Molecular Toxicology 33, no. 2: e22244.
Although there were a lot of weakly active animal toxins in the venoms, their values and applications are still mysterious, such as BF9, which is a Kunitz-type toxin isolated from the venom of the elapid snake Bungarus fasciatus. Here, we used BF9 to be a molecular scaffold, and engineered eight BF9-derived peptides by changing P1 site Asn17 of BF9, such as BF9-N17Y and BF9-N17T designed from the polar subfamily, BF9-N17L and BF9-N17G designed from the Non-polar subfamily, BF9-N17D designed from acidic subfamily, and BF9-N17H, BF9-N17K and BF9-N17R designed from basic subfamily. Through enzyme inhibitor experiment assays, we found a potent and selective chymotrypsin inhibitor BF9-N17Y, a potent and selective coagulation factor XIa inhibitor BF9-N17H, and two highly potent coagulation factor XIa inhibitors BF9-N17K and BF9-N17. APTT and PT assays further showed that BF9-N17H, BF9-N17K and BF9-N17R were three novel anticoagulants with selectively intrinsic coagulation pathway inhibitory activity. Considering that natural weakly active animal toxins are also a huge peptide resource, our present work might open a new window about pharmacological applications of weakly active animal toxins, which might be good templates for potent and selective molecular probe and lead drug designs.
Li Ding; Jinbo Hao; Xudong Luo; Zongyun Chen. Engineering varied serine protease inhibitors by converting P1 site of BF9, a weakly active Kunitz-type animal toxin. International Journal of Biological Macromolecules 2018, 120, 1190 -1197.
AMA StyleLi Ding, Jinbo Hao, Xudong Luo, Zongyun Chen. Engineering varied serine protease inhibitors by converting P1 site of BF9, a weakly active Kunitz-type animal toxin. International Journal of Biological Macromolecules. 2018; 120 ():1190-1197.
Chicago/Turabian StyleLi Ding; Jinbo Hao; Xudong Luo; Zongyun Chen. 2018. "Engineering varied serine protease inhibitors by converting P1 site of BF9, a weakly active Kunitz-type animal toxin." International Journal of Biological Macromolecules 120, no. : 1190-1197.
The Kv1.3 channel plays potential roles in immune, inflammation and coagulation system. Many studies showed that Kv1.3 channel inhibitors have immunosuppressive and anti-inflammatory activities, but no Kv1.3 channel inhibitors have been found to have anticoagulation activities. Here, based on our previous work about Kv1.3 channel toxin peptide inhibitors, we first attempt to test anticoagulation activities of four known venom-derived Kv1.3 channel inhibitors with different structural folds: BmKTX with CSα/β structural fold, OmTx3 with CSα/α structural fold, BF9 with Kuntz-type structural fold, and SjAPI-2 with Ascaris-type structural fold. Our results showed that BmKTX and OmTx3 have no activities towards both intrinsic and extrinsic coagulation pathway, SjAPI-2 just has weak activity towards intrinsic coagulation pathway, and BF9 has potent activity towards intrinsic coagulation pathway with no apparent effect on extrinsic coagulation pathway. Enzyme and inhibitor reaction kinetics experiments further showed that BF9 inhibited intrinsic coagulation pathway-associated coagulation factor XIa, but have no apparent effects on common coagulation pathway coagulation factor IIa. Structure-activity relationship showed that Gly14, Asn17, Ala18 and Ile20 of BF9 are main residues involved in the inhibiting effect on factor XIa. To the best of our knowledge, BF9 is the first anticoagulant with Kv1.3 channel inhibitory activity. Together, our present studies found the first dual functional peptides with Kv1.3 channel and coagulation factor XIa inhibitory activities, and provided a new molecular template for the lead drug discovery towards immune and thrombosis-associated human diseases.
Li Ding; Jinbo Hao; Xudong Luo; Wen Zhu; Zheng Wu; Yi Qian; Fangfang Hu; Tianli Liu; Xuzhi Ruan; Shan Li; Jian Li; Zongyun Chen. The Kv1.3 channel-inhibitory toxin BF9 also displays anticoagulant activity via inhibition of factor XIa. Toxicon 2018, 152, 9 -15.
AMA StyleLi Ding, Jinbo Hao, Xudong Luo, Wen Zhu, Zheng Wu, Yi Qian, Fangfang Hu, Tianli Liu, Xuzhi Ruan, Shan Li, Jian Li, Zongyun Chen. The Kv1.3 channel-inhibitory toxin BF9 also displays anticoagulant activity via inhibition of factor XIa. Toxicon. 2018; 152 ():9-15.
Chicago/Turabian StyleLi Ding; Jinbo Hao; Xudong Luo; Wen Zhu; Zheng Wu; Yi Qian; Fangfang Hu; Tianli Liu; Xuzhi Ruan; Shan Li; Jian Li; Zongyun Chen. 2018. "The Kv1.3 channel-inhibitory toxin BF9 also displays anticoagulant activity via inhibition of factor XIa." Toxicon 152, no. : 9-15.
Non-Buthidae venomous scorpions are huge natural sources of toxin peptides; however, only a few studies have been done to understand their toxin peptides. Herein, we describe three new potential immunomodulating toxin peptides, Ctri18, Ctry68 and Ctry2908, from two non-Buthidae scorpions, Chaerilus tricostatus and Chaerilus tryznai. Sequence alignment analyses showed that Ctri18, Ctry68 and Ctry2908 are three new members of the scorpion toxin α-KTx15 subfamily. Electrophysiological experiments showed that Ctri18, Ctry68 and Ctry2908 blocked the Kv1.3 channel at micromole to nanomole levels, but had weak effects on potassium channel KCNQ1 and sodium channel Nav1.4, which indicated that Ctri18, Ctry68 and Ctry2908 might have specific inhibiting effects on the Kv1.3 channel. ELISA experiments showed that Ctri18, Ctry68 and Ctry2908 inhibited IL-2 cytokine secretions of activated T lymphocyte in human PBMCs. Excitingly, consistent with the good Kv1.3 channel inhibitory activity, Ctry2908 inhibited cytokine IL-2 secretion in nanomole level, which indicated that Ctry2908 might be a new lead drug template toward Kv1.3 channels. Together, these studies discovered three new toxin peptides, Ctri18, Ctry68 and Ctry2908, with Kv1.3 channel and IL-2 cytokine-inhibiting activities from two scorpions, C. tricostatus and C. tryznai, and highlighted that non-Buthidae venomous scorpions are new natural toxin peptide sources.
Li Ding; Jing Chen; Jinbo Hao; Jiahui Zhang; Xuejun Huang; Fangfang Hu; Zheng Wu; Yaru Liu; Wenxin Li; Zhijian Cao; Yingliang Wu; Jian Li; Shan Li; Hongyan Liu; Wenlong Wu; Zongyun Chen. Discovery of three toxin peptides with Kv1.3 channel and IL-2 cytokine-inhibiting activities from Non-Buthidae scorpions, Chaerilus tricostatus and Chaerilus tryznai. Peptides 2017, 91, 13 -19.
AMA StyleLi Ding, Jing Chen, Jinbo Hao, Jiahui Zhang, Xuejun Huang, Fangfang Hu, Zheng Wu, Yaru Liu, Wenxin Li, Zhijian Cao, Yingliang Wu, Jian Li, Shan Li, Hongyan Liu, Wenlong Wu, Zongyun Chen. Discovery of three toxin peptides with Kv1.3 channel and IL-2 cytokine-inhibiting activities from Non-Buthidae scorpions, Chaerilus tricostatus and Chaerilus tryznai. Peptides. 2017; 91 ():13-19.
Chicago/Turabian StyleLi Ding; Jing Chen; Jinbo Hao; Jiahui Zhang; Xuejun Huang; Fangfang Hu; Zheng Wu; Yaru Liu; Wenxin Li; Zhijian Cao; Yingliang Wu; Jian Li; Shan Li; Hongyan Liu; Wenlong Wu; Zongyun Chen. 2017. "Discovery of three toxin peptides with Kv1.3 channel and IL-2 cytokine-inhibiting activities from Non-Buthidae scorpions, Chaerilus tricostatus and Chaerilus tryznai." Peptides 91, no. : 13-19.
Ordinary screening of transfusion-transmissible infections (TTIs) among blood donors is essential for blood transfusion. Although there is several TTIs studies focus on human immunodeficiency virus, hepatitis B and C viruses, and Treponema pallidum infections in China, it is no data to illustrate any firm conclusion from Shiyan City, Central China. It aims to verify the seroprevalence of TTIs among blood donors at Shiyan. A retrospective analysis of blood donors’ information was conducted for the presence of HIV, HBV, HCV and T. pallidum. Logistic regression analysis was used to demonstrate risk factors including age, gender and occupation associated with them. The variation tendency in seroprevalence of these TTIs over the study period was evaluated by Cochran-Armitage trend test. Of 211 639 blood donors, 2 858 (1.35 %) had serological evidence of TTIs. The seroprevalence of HIV, HBV, HCV and T. pallidum were 0.08 %, 0.51 %, 0.20 % and 0.57 %, respectively. However, the co-infection prevalence of TTIs has not been detected. The HIV seropositivity significantly increased among female donors (OR = 1.63, P < 0.001) and farmers (OR = 2.02, P = 0.020). Significantly increased HBV seropositivity was only observed framers (OR = 1.87, P <0.001) compared to workers. Analogously, significantly increased HCV seropositivity was observed among farmers (OR = 2.59, P < 0.001), students (OR = 2.43, P < 0.001), merchants (OR = 1.70, P = 0.014) and others (OR = 1.78, P =0.001). The T. pallidum seroprevalence was notably increased among female (OR = 1.54, P < 0.001), and farmers (OR = 1.70, P <0.001). Moreover, significantly increasing trends of HIV (Z = −6.88, P < 0.01), HBV (Z = −4.52, P < 0.01), HCV (Z = −4.16, P < 0.01) and T. pallidum (Z = −1.36, P < 0.01) seropositivity were observed over the study period. It originally offers a substantial prevalence of TTIs among blood donors at Shiyan, Central China. Severe blood donor selection and all-inclusive screening of blood are highly recommended. It might be helpful for developing and updating guidance for blood safety. Retrospectively registered.
Shuguo Yang; Danmei Jiao; Changjun Liu; Ming Lv; Shan Li; Zongyun Chen; Yao Deng; Yanqing Zhao; Jian Li. Seroprevalence of human immunodeficiency virus, hepatitis B and C viruses, and Treponema pallidum infections among blood donors at Shiyan, Central China. BMC Infectious Diseases 2016, 16, 531 .
AMA StyleShuguo Yang, Danmei Jiao, Changjun Liu, Ming Lv, Shan Li, Zongyun Chen, Yao Deng, Yanqing Zhao, Jian Li. Seroprevalence of human immunodeficiency virus, hepatitis B and C viruses, and Treponema pallidum infections among blood donors at Shiyan, Central China. BMC Infectious Diseases. 2016; 16 (1):531.
Chicago/Turabian StyleShuguo Yang; Danmei Jiao; Changjun Liu; Ming Lv; Shan Li; Zongyun Chen; Yao Deng; Yanqing Zhao; Jian Li. 2016. "Seroprevalence of human immunodeficiency virus, hepatitis B and C viruses, and Treponema pallidum infections among blood donors at Shiyan, Central China." BMC Infectious Diseases 16, no. 1: 531.
Kunitz-type peptides from venomous animals are an important source of lead drug candidates towards human plasmin, a target of protease-associated diseases. However, no Kunitz-type plasmin inhibitor from venomous scorpion has been characterized. Here, we first investigated plasmin inhibiting activities of eight known Kunitz-type scorpion toxins Hg1, BmKTT-1, BmKTT-2, BmKTT-3, LmKTT-1a, LmKTT-1b, LmKTT-1c and BmKPI, and found a new plasmin inhibitor BmKTT-2, a Kunitz-type toxin peptide from the scorpion Buthus martensi karch. Protease inhibitory activity assay showed that BmKTT-2 potently inhibited plasmin with a Ki value of 8.75 ± 2.05 nM. Structure–function relationship studies between BmKTT-2 and plasmin showed that BmKTT-2 is a classical Kunitz-type plasmin inhibitor: Lys13 in BmKTT-2 is the P1 site, and Ala14 in BmKTT-2 is the P1′ site. Interestingly, BmKTT-2 has potent inhibiting activities towards three important digestive serine proteases trypsin, chymotrypsin and elastase, suggesting a good stability for administering oral medications. To the best of our knowledge, BmKTT-2 is the first Kunitz-type human plasmin inhibitor from scorpion venom, providing novel insights into drug developments targeting human plasmin protease.
Li Ding; Xiaobo Wang; Hongyan Liu; Mingkui San; Yue Xu; Jian Li; Shan Li; Zhijian Cao; Wenxin Li; Yingliang Wu; Zongyun Chen. A new Kunitz-type plasmin inhibitor from scorpion venom. Toxicon 2015, 106, 7 -13.
AMA StyleLi Ding, Xiaobo Wang, Hongyan Liu, Mingkui San, Yue Xu, Jian Li, Shan Li, Zhijian Cao, Wenxin Li, Yingliang Wu, Zongyun Chen. A new Kunitz-type plasmin inhibitor from scorpion venom. Toxicon. 2015; 106 ():7-13.
Chicago/Turabian StyleLi Ding; Xiaobo Wang; Hongyan Liu; Mingkui San; Yue Xu; Jian Li; Shan Li; Zhijian Cao; Wenxin Li; Yingliang Wu; Zongyun Chen. 2015. "A new Kunitz-type plasmin inhibitor from scorpion venom." Toxicon 106, no. : 7-13.
Peptides with Ascaris-type fold are a new kind of toxins founded from venomous animals recently. Functionally, these unique toxin peptides had been identified as potent protease inhibitors, which was similar to other known Ascaris-type peptides from non-venomous animals. Whether Ascaris-type peptides from venom animals have neurotoxin activities remains unclear. Here, a scorpion toxin SjAPI-2 with Ascaris-type fold was characterized to have a neurotoxin activity, which can selectively inhibit KCNQ1 potassium channel. SjAPI-2 had 62 amino acid residues, including 10 cysteine residues. Charged residue analyses showed that two acidic residues of SjAPI-2 were regionally distributed, and 10 basic residues were distributed widely throughout the whole peptide, which was similar to classical potassium channel toxins. Pharmacological studies confirmed that SjAPI-2 was a selective KCNQ1 potassium channel inhibitor with weak effects on other potassium channels, such as Kv1.1, Kv1.2, Kv1.3, SKCa2, SKCa3, and IKCa channels. Concentration-dependent studies showed that SjAPI-2 inhibited the KCNQ1 potassium channel with an IC50 of 771.5±169.9 nM. To the best of our knowledge, SjAPI-2 is the first neurotoxin with a unique Ascaris-type fold, providing novel insights into the divergent evolution of neurotoxins from venomous animals.
Jing Chen; Chuangeng Zhang; Weishan Yang; Zhijian Cao; Wenxin Li; Zongyun Chen; Yingliang Wu. SjAPI-2 is the first member of a new neurotoxin family with Ascaris-type fold and KCNQ1 inhibitory activity. International Journal of Biological Macromolecules 2015, 79, 504 -510.
AMA StyleJing Chen, Chuangeng Zhang, Weishan Yang, Zhijian Cao, Wenxin Li, Zongyun Chen, Yingliang Wu. SjAPI-2 is the first member of a new neurotoxin family with Ascaris-type fold and KCNQ1 inhibitory activity. International Journal of Biological Macromolecules. 2015; 79 ():504-510.
Chicago/Turabian StyleJing Chen; Chuangeng Zhang; Weishan Yang; Zhijian Cao; Wenxin Li; Zongyun Chen; Yingliang Wu. 2015. "SjAPI-2 is the first member of a new neurotoxin family with Ascaris-type fold and KCNQ1 inhibitory activity." International Journal of Biological Macromolecules 79, no. : 504-510.
Although many studies concerning the sensitivity mechanism of scorpion toxin-potassium channel interactions have been reported, few have explored the biochemical insensitivity mechanisms of potassium channel receptors toward natural scorpion toxin peptides, such as the KCNQ1 channel. Here, by sequence alignment analyses of the human KCNQ1 channel and scorpion potassium channel MmKv2, which is completely insensitive to scorpion toxins, we proposed that the insensitivity mechanism of KCNQ1 toward natural scorpion toxins might involve two functional regions, the turret and filter regions. Based on this observation, a series of KCNQ1 mutants were constructed to study molecular mechanisms of the KCNQ1 channel insensitivity toward natural scorpion toxins. Electrophysiological studies of chimera channels showed that the channel filter region controls KCNQ1 insensitivity toward the classical scorpion toxin ChTX. Interestingly, further residue mutant experiments showed that a single basic residue in the filter region determined the insensitivity of KCNQ1 channels toward scorpion toxins. Our present work showed that amino acid residue diversification at common sites controls the sensitivity and insensitivity of potassium channels toward scorpion toxins. The unique insensitivity mechanism of KCNQ1 toward natural scorpion toxins will accelerate the rational design of potent peptide inhibitors toward this channel.
Zongyun Chen; Youtian Hu; Bin Wang; Zhijian Cao; Wenxin Li; Yingliang Wu. A single conserved basic residue in the potassium channel filter region controls KCNQ1 insensitivity toward scorpion toxins. Biochemistry and Biophysics Reports 2015, 3, 62 -67.
AMA StyleZongyun Chen, Youtian Hu, Bin Wang, Zhijian Cao, Wenxin Li, Yingliang Wu. A single conserved basic residue in the potassium channel filter region controls KCNQ1 insensitivity toward scorpion toxins. Biochemistry and Biophysics Reports. 2015; 3 ():62-67.
Chicago/Turabian StyleZongyun Chen; Youtian Hu; Bin Wang; Zhijian Cao; Wenxin Li; Yingliang Wu. 2015. "A single conserved basic residue in the potassium channel filter region controls KCNQ1 insensitivity toward scorpion toxins." Biochemistry and Biophysics Reports 3, no. : 62-67.
Among the three extracellular domains of the tetrameric voltage-gated K+ (Kv) channels consisting of six membrane-spanning helical segments named S1 through S6, the functional role of the S1-S2 linker still remains unclear due to the lack of a peptide ligand. In this study, the Kv1.3 channel S1-S2 linker was reported as a novel receptor site for human β-defensin 2 (hBD2). hBD2 shifts the conductance-voltage relationship curve of the human Kv1.3 channel in a positive direction by nearly 10.5 mV and increases the activation time constant for the channel. Unlike classical gating modifiers of toxin peptides from animal venoms, which generally bind to the Kv channel S3-S4 linker, hBD2 only targets residues in both the N- and C-terminals of the S1-S2 linker to influence channel gating and inhibit channel currents. The increment and decrement of the basic residue number in a positively charged S4 sensor of Kv1.3 channel yields conductance-voltage relationship curves in the positive direction by approximately 31.2 mV and 2-4 mV, which suggests that positively charged hBD2 is anchored in the channel S1-S2 linker and is modulating channel activation through electrostatic repulsion with an adjacent S4 helix. Together, these findings reveal a novel peptide ligand that binds with the Kv channel S1-S2 linker to modulate channel activation. These findings also highlight the functional importance of the Kv channel S1-S2 linker in ligand recognition and modification of channel activation.
Jing Feng; Weishan Yang; Zili Xie; Fang Xiang; Zhijian Cao; Wenxin Li; Hongzhen Hu; Zongyun Chen; Yingliang Wu. Kv Channel S1-S2 Linker Working as a Binding Site of Human β-Defensin 2 for Channel Activation Modulation. Journal of Biological Chemistry 2015, 290, 15487 -15495.
AMA StyleJing Feng, Weishan Yang, Zili Xie, Fang Xiang, Zhijian Cao, Wenxin Li, Hongzhen Hu, Zongyun Chen, Yingliang Wu. Kv Channel S1-S2 Linker Working as a Binding Site of Human β-Defensin 2 for Channel Activation Modulation. Journal of Biological Chemistry. 2015; 290 (25):15487-15495.
Chicago/Turabian StyleJing Feng; Weishan Yang; Zili Xie; Fang Xiang; Zhijian Cao; Wenxin Li; Hongzhen Hu; Zongyun Chen; Yingliang Wu. 2015. "Kv Channel S1-S2 Linker Working as a Binding Site of Human β-Defensin 2 for Channel Activation Modulation." Journal of Biological Chemistry 290, no. 25: 15487-15495.
Human potassium channels are widely inhibited by peptide toxins from venomous animals. However, no human endogenous peptide inhibitor has been discovered so far. In this study, we demonstrate for the first time using electrophysiological techniques, that endogenous human β–defensin 2 (hBD2) is able to selectively and dose-dependently inhibit the human voltage-gated Kv1.3 channel at picomolar peptide concentration. The co-immunoprecipitation assays further supported the selective binding of hBD2 to Kv1.3 channel. Using mutagenesis experiments, we found that the outer pore domain of Kv1.3 channel was the binding site of hBD2, which is similar to the interacting site of Kv1.3 channel recognized by animal toxin inhibitors. The hBD2 was able to suppress IL-2 production through inhibition of Kv1.3 channel currents in human Jurkat cells, which was further confirmed by the lack of hBD2 activity on IL-2 production after Kv1.3 knockdown in these cells. More interestingly, hBD2 was also found to efficiently inhibit Kv1.3 channel currents and suppress IL-2 production in both human primary CD3+ T cells and peripheral mononuclear cells from either healthy donors or psoriasis patients. Our findings not only evidenced hBD2 as the first characterized endogenous peptide inhibitor of human potassium channels, but also paved a promising avenue to investigate newly discovered function of hBD2 as Kv1.3 channel inhibitor in the immune system and other fields.
Weishan Yang; Jing Feng; Fang Xiang; Zili Xie; GuoYi Zhang; Jean-Marc Sabatier; Zhijian Cao; Wenxin Li; Zongyun Chen; Yingliang Wu. Endogenous animal toxin-like human β-defensin 2 inhibits own K+ channels through interaction with channel extracellular pore region. Cellular and Molecular Life Sciences 2014, 72, 845 -853.
AMA StyleWeishan Yang, Jing Feng, Fang Xiang, Zili Xie, GuoYi Zhang, Jean-Marc Sabatier, Zhijian Cao, Wenxin Li, Zongyun Chen, Yingliang Wu. Endogenous animal toxin-like human β-defensin 2 inhibits own K+ channels through interaction with channel extracellular pore region. Cellular and Molecular Life Sciences. 2014; 72 (4):845-853.
Chicago/Turabian StyleWeishan Yang; Jing Feng; Fang Xiang; Zili Xie; GuoYi Zhang; Jean-Marc Sabatier; Zhijian Cao; Wenxin Li; Zongyun Chen; Yingliang Wu. 2014. "Endogenous animal toxin-like human β-defensin 2 inhibits own K+ channels through interaction with channel extracellular pore region." Cellular and Molecular Life Sciences 72, no. 4: 845-853.