17 results on '"Zhi Jian Cao"'
Search Results
2. Efficacy of Aeschynomene indica L. leaves for wound healing and isolation of active constituent
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Mingzhang Ao, Zhi-Jian Cao, Longjiang Yu, Jing-Jing Chen, and Zhi-Yong Lei
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Male ,Pathology ,medicine.medical_specialty ,Angiogenesis ,Dalbergia ,H&E stain ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,In vivo ,Drug Discovery ,medicine ,Animals ,Rats, Wistar ,Fibroblast ,Skin ,030304 developmental biology ,Pharmacology ,Wound Healing ,0303 health sciences ,integumentary system ,Eosin ,Plant Extracts ,CD68 ,business.industry ,Macrophages ,Staining ,Plant Leaves ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Wound healing ,business ,Phytotherapy - Abstract
Ethnopharmacological relevance In traditional Chinese medicine, the aerial parts of Aeschynomene indica L. (AIL) have been used for wound healing, and to treat urinary tract infection, hepatitis, enteritis, dysentery, nyctalopia, conjunctivitis, urticaria, and furuncle. However, no scientific investigation has been conducted on its wound healing potential. Aim of the study To investigate the effects of AIL extract on wound healing, isolate the active constituent and reveal the possible mechanism of enhancing wound healing. Materials and methods The circular excision wound healing model was used to evaluate in vivo wound-healing activity. Hematoxylin and eosin staining was applied to assess inflammatory cells infiltration, angiogenesis, fibroblast proliferation, collagen synthesis, collagen remodeling, and skin appendages generation. Sirius red-picric acid staining was employed for quantitative analysis of the ratio of collagen I/III. Immunohistochemical staining for CD68, CCR7 (CD197), CD163, TGF-β1 and α-SMA was performed to determine macrophages phenotypes transition (M1-to-M2) and prove the scar-improving effect of AIL on wound healing. Results We successfully isolated the active constituent (Sub-Fr0.2) for wound healing from AIL extract, circular excision wound healing experiment and hematoxylin & eosin staining showed Sub-Fr0.2 has a significant promoting effect on wound healing. Results of sirius red-picric acid staining demonstrated a reduced ratio of collagen I/III in the Sub-Fr0.2 group as compared with the vehicle group. Immunohistochemical staining for CD68, CCR7 (CD197), and CD163 in the Sub-Fr0.2 group exhibited an elevated speed of macrophages transiting from M1 phenotype to M2 phenotype, when compared with the vehicle group. Besides, the expression of TGF-β1 and α-SMA were inhibited on wounds treated with the ointment containing Sub-Fr0.2. Conclusion Leaves of AIL and its active constituent (Sub-Fr0.2) effectively promoted wound healing and reduced scar formation, this efficacy might be exerted by accelerating macrophages phenotypes transition and inhibiting TGF-β1 and α-SMA expression.
- Published
- 2019
3. Structural and functional diversity of acidic scorpion potassium channel toxins.
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Zong-Yun Chen, Dan-Yun Zeng, You-Tian Hu, Ya-Wen He, Na Pan, Jiu-Ping Ding, Zhi-Jian Cao, Mai-Li Liu, Wen-Xin Li, Hong Yi, Ling Jiang, and Ying-Liang Wu
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Medicine ,Science - Abstract
BACKGROUND: Although the basic scorpion K(+) channel toxins (KTxs) are well-known pharmacological tools and potential drug candidates, characterization the acidic KTxs still has the great significance for their potential selectivity towards different K(+) channel subtypes. Unfortunately, research on the acidic KTxs has been ignored for several years and progressed slowly. PRINCIPAL FINDINGS: Here, we describe the identification of nine new acidic KTxs by cDNA cloning and bioinformatic analyses. Seven of these toxins belong to three new α-KTx subfamilies (α-KTx28, α-KTx29, and α-KTx30), and two are new members of the known κ-KTx2 subfamily. ImKTx104 containing three disulfide bridges, the first member of the α-KTx28 subfamily, has a low sequence homology with other known KTxs, and its NMR structure suggests ImKTx104 adopts a modified cystine-stabilized α-helix-loop-β-sheet (CS-α/β) fold motif that has no apparent α-helixs and β-sheets, but still stabilized by three disulfide bridges. These newly described acidic KTxs exhibit differential pharmacological effects on potassium channels. Acidic scorpion toxin ImKTx104 was the first peptide inhibitor found to affect KCNQ1 channel, which is insensitive to the basic KTxs and is strongly associated with human cardiac abnormalities. ImKTx104 selectively inhibited KCNQ1 channel with a K(d) of 11.69 µM, but was less effective against the basic KTxs-sensitive potassium channels. In addition to the ImKTx104 toxin, HeTx204 peptide, containing a cystine-stabilized α-helix-loop-helix (CS-α/α) fold scaffold motif, blocked both Kv1.3 and KCNQ1 channels. StKTx23 toxin, with a cystine-stabilized α-helix-loop-β-sheet (CS-α/β) fold motif, could inhibit Kv1.3 channel, but not the KCNQ1 channel. CONCLUSIONS/SIGNIFICANCE: These findings characterize the structural and functional diversity of acidic KTxs, and could accelerate the development and clinical use of acidic KTxs as pharmacological tools and potential drugs.
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- 2012
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4. Rosehip Oil Promotes Excisional Wound Healing by Accelerating the Phenotypic Transition of Macrophages
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Wenwen Jin, Longjiang Yu, Zaiwang Yang, Mingzhang Ao, Zhi-Yong Lei, and Zhi-Jian Cao
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Male ,Pathology ,medicine.medical_specialty ,H&E stain ,Pharmaceutical Science ,Scars ,Rosa ,01 natural sciences ,Gas Chromatography-Mass Spectrometry ,Analytical Chemistry ,Mice ,Antigens, CD ,Fibrosis ,Drug Discovery ,Poor wound healing ,medicine ,Animals ,Plant Oils ,Macrophage ,Rats, Wistar ,Pharmacology ,Wound Healing ,integumentary system ,010405 organic chemistry ,CD68 ,business.industry ,Macrophages ,Organic Chemistry ,Cell Differentiation ,medicine.disease ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Phenotype ,Complementary and alternative medicine ,Molecular Medicine ,medicine.symptom ,Wound healing ,business ,CD163 - Abstract
Poor wound healing is a major and global threat to public health. Efforts have been made to better understand the underlying mechanisms and develop effective remedies, though the advancements that have been made are still limited. As there are no effective and generally applicable therapies available for skin injuries and fibrosis, it is urgent to develop new drugs and therapies that facilitate wound healing and effectively improve scars. In this study, GC-MS analysis was performed to identify the chemical composition of rosehip oil. The excisional wound healing model and the carrageenan-induced paw edema method were respectively applied to evaluate the wound healing activity and anti-inflammatory activity of rosehip oil. Hematoxylin and eosin staining was used to assess the pathological changes of sections, and Sirius-red staining was performed to analyze the ratio of collagen I/III in wound tissues. Immunohistological staining for CD68, CCR7 (CD197), CD163, TGF-β1, and α-SMA was applied to determine the macrophage phenotypes transition (M1-to-M2) and demonstrate the scar-improving efficacy of rosehip oil on wound healing. Results showed that rosehip oil significantly promoted wound healing and effectively improved scars. This efficacy might be exerted by accelerating the macrophage phenotypes transition and inhibiting the process of epithelial-mesenchymal transition.
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- 2018
5. The scorpions of Hainan Island, China (Arachnida: Scorpiones)
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Lin Zhu, Zhiyong Di, Ying-Liang Wu, Wen-Xin Li, Hui Liu, and Zhi-Jian Cao
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Geography ,biology ,Hemiscorpiidae ,Ecology ,Buthidae ,Fauna ,biology.organism_classification ,China - Published
- 2013
6. The first record of the family Euscorpiidae (Arachnida: Scorpiones) from Central China, with a key of Chinese species of the genus Scorpiops
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Wen-Xin Li, Zhi-Jian Cao, Yingliang Wu, Zhiyong Di, and Yawen He
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Geography ,biology ,Genus ,Zoology ,Key (lock) ,Central china ,Euscorpiidae ,biology.organism_classification - Published
- 2011
7. A convenient cell fusion assay for the study of SARS‐CoV entry and inhibition
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Ying Zhu, Da He Jiang, Wen Lan Wu, Xin Mao, Rui Gong, Zhi Jian Cao, Wenxin Li, Ying Liang Wu, Hui Liu, Xiu Ling Xu, and Yong Gang Sha
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fusion inhibition ,Time Factors ,viruses ,Clinical Biochemistry ,Green Fluorescent Proteins ,ACE2 ,Biology ,Peptidyl-Dipeptidase A ,Severe Acute Respiratory Syndrome ,Biochemistry ,Article ,Flow cytometry ,S protein ,Cell Fusion ,Viral Envelope Proteins ,Viral entry ,Chlorocebus aethiops ,Genetics ,medicine ,Escherichia coli ,Animals ,Trypsin ,cell‐to‐cell fusion assay ,Molecular Biology ,Fluorescent Dyes ,Glutathione Transferase ,Syncytium ,COS cells ,Cell fusion ,Membrane Glycoproteins ,medicine.diagnostic_test ,Ligand binding assay ,SARS‐CoV ,Cell Biology ,Articles ,Molecular biology ,Coculture Techniques ,Recombinant Proteins ,Cell biology ,Luminescent Proteins ,Severe acute respiratory syndrome-related coronavirus ,Cell culture ,COS Cells ,Spike Glycoprotein, Coronavirus ,Biological Assay ,Angiotensin-Converting Enzyme 2 ,Peptides ,Fusion mechanism - Abstract
SARS‐CoV spike (S) protein‐mediated cell fusion is important for the viral entry mechanism and identification of SARS‐CoV entry inhibitors. In order to avoid the high risks involved in handling SARS‐CoV and to facilitate the study of viral fusion mechanism, we established the cell lines: SR‐COS7 cells that stably express both SARS‐CoV S protein and red fluorescence protein, R‐COS7 cells that stably express red fluorescence protein, and AG‐COS7 cells that stably express both ACE2 and green fluorescence protein, respectively. When SR‐COS7 cells or R‐COS7 cells were cocultured with AG‐COS7 cells, syncytia with yellow fluorescence were conveniently observed after 12 h in SR‐COS7 cells plus AG‐COS7 cells, but not in R‐COS7 cells plus AG‐COS7 cells. The cell‐to‐cell fusion efficiency was simply determined for quantitative analysis based on the number of syncytium detected by flow cytometry. Such new cell‐to‐cell fusion model was further assessed by the potent HR2 peptide inhibitor, which led to the obvious decrease of the cell‐to‐cell fusion efficiency. The successful fusion and inhibition of cell‐based binding assay shows that it can be well used for the study of SARS‐CoV entry and inhibition. iubmb Life, 58: 480 ‐ 486, 2006
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- 2008
8. Genomic Sequence Analysis and Organization of BmKαTx11 and BmKαTx15 from Buthus martensii Karsch: Molecular Evolution of α-toxin genes
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Xin Mao, Wen Lan Wu, Wenxin Li, Da He Jiang, Hui Liu, Xiu Ling Xu, Yong Gang Sha, Zhi Jian Cao, Feng Luo, and Ji Qun Sheng
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DNA, Complementary ,Sequence analysis ,Molecular Sequence Data ,Scorpion Venoms ,Locus (genetics) ,Biology ,Biochemistry ,Evolution, Molecular ,Scorpions ,Gene Duplication ,Sequence Homology, Nucleic Acid ,Complementary DNA ,Gene duplication ,Animals ,Gene family ,Amino Acid Sequence ,Molecular Biology ,Gene ,Southern blot ,Genetics ,Genome ,Base Sequence ,General Medicine ,Introns ,Blotting, Southern ,genomic DNA ,Mutation ,Gene Deletion - Abstract
Based on the reported cDNA sequences of BmKalphaTxs , the genes encoding toxin BmKalphaTx11 and BmKalphaTx15 were amplified by PCR from the Chinese scorpion Buthus martensii Karsch genomic DNA employing synthetic oligonucleotides. Sequences analysis of nucleotide showed that an intron about 500 bp length interrupts signal peptide coding regions of BmKalphaTx11 and BmKalphaTx15. Using cDNA sequence of BmKalphaTx11 as probe, southern hybridization of BmK genome total DNA was performed. The result indicates that BmKalphaTx11 is multicopy genes or belongs to multiple gene family with high homology genes. The similarity of BmKalpha-toxin gene sequences and southern hybridization revealed the evolution trace of BmKalpha-toxins: BmKalpha-toxin genes evolve from a common progenitor, and the genes diversity is associated with a process of locus duplication and gene divergence.
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- 2005
9. Open conformation of hERG channel turrets revealed by a specific scorpion toxin BmKKx2
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Jing Jing Wei, Yi Mei Du, Tian Li, Ying Liang Wu, Wenxin Li, Jun Hu, You Tian Hu, Jing Feng, and Zhi Jian Cao
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congenital, hereditary, and neonatal diseases and abnormalities ,Mesobuthus martensii ,Mutant ,hERG ,Pharmacology ,medicine.disease_cause ,Turret ,General Biochemistry, Genetics and Molecular Biology ,Molecular mechanism ,BmKKx2 ,medicine ,cardiovascular diseases ,Alanine ,Scorpion toxin ,biology ,Chemistry ,Toxin ,Research ,Mutagenesis ,hERG channel ,biology.organism_classification ,Potassium channel ,Biophysics ,biology.protein ,Pore region - Abstract
Background The human ether-a-go-go-related gene potassium channel (hERG) has an unusual long turret, whose role in recognizing scorpion toxins remains controversial. Here, BmKKx2, the first specific blocker of hERG channel derived from scorpion Mesobuthus martensii, was identified and the turret role of hERG channel was re-investigated using BmKKx2 as a molecular probe. Results BmKKx2 was found to block hERG channel with an IC50 of 6.7 ± 1.7 nM and share similar functional surface with the known hERG channel inhibitor BeKm-1. The alanine-scanning mutagenesis data indicate that different residue substitutions on hERG channel by alanine decreased the affinities of toxin BmKKx2 by about 10-fold compared with that of wild-type hERG channel, which reveals that channel turrets play a secondary role in toxin binding. Different from channel turret, the pore region of hERG channel was found to exert the conserved and essential function for toxin binding because the mutant hERG-S631A channel remarkably decreased toxin BmKKx2 affinity by about 104-fold. Conclusions Our results not only revealed that channel turrets of hERG channel formed an open conformation in scorpion toxin binding, but also enriched the diversity of structure-function relationships among the different potassium channel turrets.
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- 2014
10. [Genomic DNA sequences and functional expression, purification of BmalphaTX14 neurotoxin from scorpion Buthus martensii Karsch]
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Meng, Lü, Kun, Wang, Zhi-Jian, Cao, Da-He, Jiang, Xin, Mao, and Wen-Xin, Li
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Scorpions ,Base Sequence ,Molecular Sequence Data ,Animals ,Scorpion Venoms ,Amino Acid Sequence ,Cloning, Molecular ,Sequence Analysis ,Pichia ,Recombinant Proteins - Abstract
Based on the full-length cDNA of BmalphaTX14 from Chinese scorpion Buthus martensii Karsch (BmK), gene of the mature peptide of BmalphaTX14 was cloned into the yeast expression vector pPIC9K. After transforming, screening and inducing, tricine-SDS-PAGE and Western blot proved that rBmalphaTX14 protein was expressed in the medium for up to 84 hours, getting nearly 120 mg/L. Recombinant BmalphaTX14 was purified rapidly and efficiently through Ni-NTA-agarose, polyethylene glycol precipitation and gel filtration chromatography. The purified rBmalphaTX14 proved to have the anti-insect activity by toxicity assay. Meanwhile, genomic gene of BmalphaTX14 was cloned and sequenced by PCR method, sequence analysis of this gene showed that BmalphaTX14 had an intron of 408 base pairs located at the signal peptide encoding region, which was similar with the characteristic of other alpha-type sodium ion-channel toxin. Considering both the genomic organization and the peptide function, BmaTX14 proved to be a membership belonging to alpha-type sodium ion-channel toxin.
- Published
- 2006
11. [Analysis of the genomic organization of a novel scorpion toxin BmTXK beta]
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Fan, Xiao, Zhi-Jian, Cao, Meng, Lü, Da-He, Jiang, Xin, Mao, Hui, Liu, and Wen-Xin, Li
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Base Sequence ,Genetic Structures ,Molecular Sequence Data ,Scorpion Venoms ,Amino Acid Sequence - Abstract
Scorpion venoms contain different types of low molecular mass toxic peptides acting on ion channels. Many cDNAs and genomic genes encoding these toxins have been isolated and sequenced while the mechanisms of expression and regulation of scorpion toxins is not well studied yet. BmTXK beta, one of the four putative long-chain potassium channel toxins, is isolated from the cDNA library of the venom gland of Chinese scorpion BmK (Buthus martensii Karsch). It has an 886 bp intron located in the mature peptide while other scorpion toxins' introns are located in the signal peptide. The special genomic organization of BmTXK beta makes it a good object to study the mechanism of expression and regulation of scorpion toxins. With primers designed according to the already known sequence of BmTXK beta, its 5' and 3' flanking regions are cloned by the Vecttorette II Staorette Pack method and sequenced. Analysis of the sequence shows that another intron longer than 997 bp is located in the signal peptide region of BmTXK beta, which makes BmTXK beta different from all the other scorpion toxins that have no intron or only one intron in the signal peptide. The special genomic organization of BmTXK beta indicates that BmTXK beta is a new membership of long-chain potassium channel toxin.
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- 2003
12. The scorpions of Hainan Island, China (Arachnida: Scorpiones).
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Zhi-Yong Di, Zhi-Jian Cao, Ying-Liang Wu, Lin Zhu, Hui Liu, and Wen-Xin Li
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SCORPIONS , *ANATOMY , *ANIMAL variation , *DISSECTING microscopes - Abstract
The redescriptions and illustrations of three species, Isometrus (Isometrus) maculatus (DeGeer, 1778), Lychas mucronatus (Fabricius, 1798) (Buthidae), and Liocheles australasiae (Fabricius, 1775) (Hemiscorpiidae) from Hainan Island, China are presented. Distribution data and updated key of Hainan scorpions are provided. [ABSTRACT FROM AUTHOR]
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- 2013
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13. Different Residues in Channel Turret Determining the Selectivity of ADWX-1 Inhibitor Peptide between Kv1.1 and Kv1.3 Channels.
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Shi-Jin Yin, Ling Jiang, Hong Yi, Song Han, Dai-Wen Yang, Mai-Li Liu, Hui Liu, Zhi-Jian Cao, Ying-Liang Wu, and Wen-Xin Li
- Published
- 2008
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14. Functional analysis of the α-neurotoxin, BmαTX14, derived from the Chinese scorpion, Buthus martensii Karsch.
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Kun Wang, Shi-Jin Yin, Meng Lu, Hong Yi, Chao Dai, Xiu-Jing Xu, Zhi-Jian Cao, Ying-Liang Wu, and Wen-Xin Li
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GENE expression ,GENETIC code ,GENETIC transcription ,CELLS ,GEL permeation chromatography ,NEURONS - Abstract
The gene encoding the BmαTX14 (α-neurotoxin TX14) protein, derived from the cDNA library of the Chinese scorpion Buthus martensii Karsch, was expressed in Pichia pastoris. The recombinant protein was purified by metal chelate affinity chromatography and gel filtration chromatography. Using patch-clamp technique, electrophysiological activity of rBmαTX14 was identified. In the neurons isolated from mice trigeminal root ganglion, the Na
+ current amplitude was reduced by 80% under whole cell patch-clamp recording. There were no apparent modifications to the gating mechanism in the presence of rBmαTX14. Although BmαTX14 shared a high amino acid sequence similarity with other typical α-toxins, it has different effects on neurons. Further electrophysiological analysis suggested that rBmαTX14 selectively blocked Na+ channels and is a member of a new group of scorpion toxins. [ABSTRACT FROM AUTHOR]- Published
- 2006
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15. Anti-osteoporosis effect of Cistanche deserticola Ma extract in ovariectomized rats.
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Li Zhang, Xin-Xia Yue, Lei Zhang, Jin-Fang Zhao, Yi-min Chen, Zhi-jian Cao, and Yong-lin Liu
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ORAL medication , *DRUG dosage , *OSTEOPOROSIS treatment , *OVARIECTOMY , *BONE density , *LABORATORY rats - Abstract
Purpose: To investigate the therapeutic effects of Cistanche deserticola Ma. extract (CDME) on ovariectomy-induced osteoporosis in rats. Methods: Female Sprague-Dawley rats were randomly assigned to a control group and five ovariectomy (OVX) subgroups, that is, OVX with vehicle (OVX), OVX with 17ß-estradiol (E2, 25 μg/kg/day), and OVX with CDME doses (40, 80, or 160 mg/kg/day). Daily oral administration of E2 or CDME started 4 weeks after OVX and lasted for 16 weeks. Bone mineral density (BMD) of L4 vertebrae and right femur of rats was estimated, The length of each femur was measured, and biochemical analysis of serum and urine specimens were performed. Results: CDME dose-dependently inhibited the reduction in BMD of L4 vertebrae (0.23 ± 0.02 g/cm3, p < 0.05) and femurs (0.20 ± 0.03 g/cm3, p < 0.05) caused by OVX and prevented the deterioration of trabecular microarchitecture (p < 0.05), which were accompanied by a significant decrease in skeletal remodeling (p < 0.05) as evidenced by the lower levels of bone turnover markers. Conclusion: This study indicates that CDME prevents OVX-induced osteoporosis in rats, and could be used for treating osteoporosis in elderly women. [ABSTRACT FROM AUTHOR]
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- 2016
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16. Hg1, Novel Peptide Inhibitor Specific for Kv1.3 Channels from First Scorpion Kunitz-type Potassium Channel Toxin Family.
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Zong-Yun Chen, You-Tian Hu, Wei-Shan Yang, Ya-Wen He, Jing Feng, Bin Wang, Rui-Ming Zhao, Jiu-Ping Ding, Zhi-Jian Cao, Wen-Xin Li, and Ying-Liang Wu
- Subjects
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MERCURY , *POTASSIUM channels , *AUTOIMMUNE diseases , *ELECTROPHYSIOLOGY , *SCORPION venom , *PHYSIOLOGY - Abstract
The potassium channel Kv1.3 is an attractive pharmacological target for autoimmune diseases. Specific peptide inhibitors are key prospects for diagnosing and treating these diseases. Here, we identified the first scorpion Kunitz-type potassium channel toxin family with three groups and seven members. In addition to their function as trypsin inhibitors with dissociation constants of 140 nM for recombinant LmKTT-1a, 160 nM for LmKTT-1b, 124 nM for LmKTT-1c, 136 nM for BmKTT-1, 420 nM for BmKTT-2, 760 nM for BmKTT-3, and 107 nM for Hg1, all seven recombinant scorpion Kunitz-type toxins could block the Kv1.3 channel. Electrophysiological experiments showed that six of seven scorpion toxins inhibited ∼50-80% of Kv1.3 channel currents at a concentration of 1μM. The exception was rBm- KTT-3, which had weak activity. The IC50 values of rBmKTT-1, rBmKTT-2, and rHg1 for Kv1.3 channels were ∼129.7, 371.3, and 6.2 nM, respectively. Further pharmacological experiments indicated that rHg1 was a highly selective Kv1.3 channel inhibitor with weak affinity for other potassium channels. Different from classical Kunitz-type potassium channel toxins with N-terminal regions as the channel-interacting interfaces, the channel- interacting interface of Hg1 was in the C-terminal region. In conclusion, these findings describe the first scorpion Kunitztype potassium channel toxin family, of which a novel inhibitor, Hg1, is specific for Kv1.3 channels. Their structural and functional diversity strongly suggest that Kunitz-type toxins are a new source to screen and design potential peptides for diagnosing and treating Kv1.3-mediated autoimmune diseases. [ABSTRACT FROM AUTHOR]
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- 2012
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17. Structural Basis of a Potent Peptide Inhibitor Designed for Kv1 .3 Channel, a Therapeutic Target of Autoimmune Disease.
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Song Han, Hong Yi, Shi-Jin Yin, Zong-Yun Chen, Hui Liu, Zhi-Jian Cao, Ying-Liang Wu, and Wen-Xin Li
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AUTOIMMUNE diseases , *AUTOIMMUNE disease treatment , *IMMUNOLOGIC diseases , *POTASSIUM channels , *IMMUNOREGULATION , *T cells - Abstract
The potassium channel Kv1.3 is an attractive pharmacological target for immunomodulation of T cell-mediated autoimmune diseases. Potent and selective blockers of Kv1.3 are potential therapeutics for treating these diseases. Here we describe the design of a new peptide inhibitor that is potent and selective for Kv1.3. Three residues (Gly11 Ile28, and Asp33) of a scorpion toxin BmKTX were substituted by Arg11, Thr28, and His33, resulting in a new peptide, named ADWX-1. The ADWX-1 peptide blocked Kv 1.3 with picomolar affinity (IC50, 1.89 pM), showing a 100-fold increase in activity compared with the native BmKTX toxin. The ADWX-1 also displayed good selectivity on Kv1.3 over related Kv1.1 and Kv1.2 channels. Furthermore, alanine-scanning mutagenesis was carried out to map the functional residues of ADWX-1 in blocking Kv1.3. Moreover, computational simulation was used to build a structural model of the ADWX-1-Kv1.3 complex. This model suggests that all mutated residues are favorable for both the high potency and selectivity of ADWX-1 toward Kv1.3. While Arg11 of ADWX-1 interacts with Asp386 in Kv1.3, Thr28 and His33 of ADWX-1 locate right above the selectivity filter-S6 linker of Kv1.3. Together, our data indicate that the specific ADWX-1 peptide would be a viable lead in the therapy of T cell-mediated autoimmune diseases, and the successful design of ADWX-1 suggests that rational design based on the structural model of the peptide-channel complex should accelerate the development of diagnostic and therapeutic agents for human channelopathies. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
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