The Experts below are selected from a list of 201 Experts worldwide ranked by ideXlab platform
Jing Yao - One of the best experts on this subject based on the ideXlab platform.
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therapeutic inhibition of keratinocyte trpv3 sensory channel by local anesthetic Dyclonine
eLife, 2021Co-Authors: Qiang Liu, Jin Wang, Xin Wei, Conghui Ping, Yue Gao, Chang Xie, Peiyu Wang, Peng Cao, Zhengyu Cao, Jing YaoAbstract:The multimodal sensory channel transient receptor potential vanilloid-3 (TRPV3) is expressed in epidermal keratinocytes and implicated in chronic pruritus, allergy, and inflammation-related skin disorders. Gain-of-function mutations of TRPV3 cause hair growth disorders in mice and Olmsted syndrome in humans. Nevertheless, whether and how TRPV3 could be therapeutically targeted remains to be elucidated. We here report that mouse and human TRPV3 channel is targeted by the clinical medication Dyclonine that exerts a potent inhibitory effect. Accordingly, Dyclonine rescued cell death caused by gain-of-function TRPV3 mutations and suppressed pruritus symptoms in vivo in mouse model. At the single-channel level, Dyclonine inhibited TRPV3 open probability but not the unitary conductance. By molecular simulations and mutagenesis, we further uncovered key residues in TRPV3 pore region that could toggle the inhibitory efficiency of Dyclonine. The functional and mechanistic insights obtained on Dyclonine-TRPV3 interaction will help to conceive therapeutics for skin inflammation.
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therapeutic inhibition of keratinocyte trpv3 sensory channels by local anesthetic Dyclonine
bioRxiv, 2020Co-Authors: Jing Yao, Qiang Liu, Jin Wang, Xin Wei, Conghui Ping, Yue Gao, Chang XieAbstract:The multimodal sensory channel transient receptor potential vanilloid-3 (TRPV3) is expressed in epidermal keratinocytes and implicated in chronic pruritus, allergy, and inflammation-related skin disorders. Gain-of-function mutations of TRPV3 cause hair growth disorders in mice and Olmsted Syndrome in human. We here report that mouse and human TRPV3 channel is selectively targeted by the clinical medication Dyclonine that exerts a potent inhibitory effect. Accordingly, Dyclonine rescued cell death caused by gain-of-function TRPV3 mutations and suppressed pruritus symptoms in vivo in mouse model. At the single-channel level, Dyclonine inhibited TRPV3 open probability but not the unitary conductance. By molecular docking and mutagenesis, we further uncovered single residues in TRPV3 pore region that could toggle the inhibitory efficiency of Dyclonine. The functional and mechanistic insights obtained on Dyclonine-TRPV3 interaction will help to conceive updated therapeutics for skin inflammation.
Youming Xie - One of the best experts on this subject based on the ideXlab platform.
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Dyclonine enhances the cytotoxic effect of proteasome inhibitor bortezomib in multiple myeloma cells
Molecular Medicine Reports, 2014Co-Authors: Youming XieAbstract:The proteasome has become an important target for cancer therapy with the approval of bortezomib for the treatment of relapsed/refractory multiple myeloma (MM). However, numerous patients with MM do not respond to bortezomib and those responding initially often acquire resistance. Recent clinical studies have also demonstrated that bortezomib is also inefficacious in the treatment of other types of cancer. Therefore, it is imperative to develop novel approaches and agents for proteasome-targeting cancer therapy. In the present study, it was revealed that Dyclonine, a major component of the cough droplets Sucrets, markedly enhances the cytotoxic effects of bortezomib and minimizes drug resistance in MM cells. It was demonstrated that a combination of bortezomib and Dyclonine markedly induced apoptosis of MM cells. The present study suggests a novel therapeutic use of an over‑the‑counter medicine for the treatment of MM.
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Dyclonine and alverine citrate enhance the cytotoxic effects of proteasome inhibitor mg132 on breast cancer cells
International Journal of Molecular Medicine, 1998Co-Authors: Xiaogang Wang, Youming XieAbstract:Proteasome is an important target in cancer therapy. To enhance the efficacy of proteasome inhibitors is a challenging task due to the paucity of understanding the functional interactions between proteasome and other cellular pathways in mammalian cells. Taking advantage of the knowledge gained from Saccharomyces cerevisiae, we show that Dyclonine and alverine citrate, the major components of two over-the-counter medicines, can substantially enhance the cytotoxic effects of proteasome inhibitor MG132 on breast cancer cells. This study also highlights an important yeast genetic approach to identification of potential therapeutics that can be used for combination therapy with proteasome inhibitors.
Qiang Liu - One of the best experts on this subject based on the ideXlab platform.
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therapeutic inhibition of keratinocyte trpv3 sensory channel by local anesthetic Dyclonine
eLife, 2021Co-Authors: Qiang Liu, Jin Wang, Xin Wei, Conghui Ping, Yue Gao, Chang Xie, Peiyu Wang, Peng Cao, Zhengyu Cao, Jing YaoAbstract:The multimodal sensory channel transient receptor potential vanilloid-3 (TRPV3) is expressed in epidermal keratinocytes and implicated in chronic pruritus, allergy, and inflammation-related skin disorders. Gain-of-function mutations of TRPV3 cause hair growth disorders in mice and Olmsted syndrome in humans. Nevertheless, whether and how TRPV3 could be therapeutically targeted remains to be elucidated. We here report that mouse and human TRPV3 channel is targeted by the clinical medication Dyclonine that exerts a potent inhibitory effect. Accordingly, Dyclonine rescued cell death caused by gain-of-function TRPV3 mutations and suppressed pruritus symptoms in vivo in mouse model. At the single-channel level, Dyclonine inhibited TRPV3 open probability but not the unitary conductance. By molecular simulations and mutagenesis, we further uncovered key residues in TRPV3 pore region that could toggle the inhibitory efficiency of Dyclonine. The functional and mechanistic insights obtained on Dyclonine-TRPV3 interaction will help to conceive therapeutics for skin inflammation.
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therapeutic inhibition of keratinocyte trpv3 sensory channels by local anesthetic Dyclonine
bioRxiv, 2020Co-Authors: Jing Yao, Qiang Liu, Jin Wang, Xin Wei, Conghui Ping, Yue Gao, Chang XieAbstract:The multimodal sensory channel transient receptor potential vanilloid-3 (TRPV3) is expressed in epidermal keratinocytes and implicated in chronic pruritus, allergy, and inflammation-related skin disorders. Gain-of-function mutations of TRPV3 cause hair growth disorders in mice and Olmsted Syndrome in human. We here report that mouse and human TRPV3 channel is selectively targeted by the clinical medication Dyclonine that exerts a potent inhibitory effect. Accordingly, Dyclonine rescued cell death caused by gain-of-function TRPV3 mutations and suppressed pruritus symptoms in vivo in mouse model. At the single-channel level, Dyclonine inhibited TRPV3 open probability but not the unitary conductance. By molecular docking and mutagenesis, we further uncovered single residues in TRPV3 pore region that could toggle the inhibitory efficiency of Dyclonine. The functional and mechanistic insights obtained on Dyclonine-TRPV3 interaction will help to conceive updated therapeutics for skin inflammation.
Chang Xie - One of the best experts on this subject based on the ideXlab platform.
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therapeutic inhibition of keratinocyte trpv3 sensory channel by local anesthetic Dyclonine
eLife, 2021Co-Authors: Qiang Liu, Jin Wang, Xin Wei, Conghui Ping, Yue Gao, Chang Xie, Peiyu Wang, Peng Cao, Zhengyu Cao, Jing YaoAbstract:The multimodal sensory channel transient receptor potential vanilloid-3 (TRPV3) is expressed in epidermal keratinocytes and implicated in chronic pruritus, allergy, and inflammation-related skin disorders. Gain-of-function mutations of TRPV3 cause hair growth disorders in mice and Olmsted syndrome in humans. Nevertheless, whether and how TRPV3 could be therapeutically targeted remains to be elucidated. We here report that mouse and human TRPV3 channel is targeted by the clinical medication Dyclonine that exerts a potent inhibitory effect. Accordingly, Dyclonine rescued cell death caused by gain-of-function TRPV3 mutations and suppressed pruritus symptoms in vivo in mouse model. At the single-channel level, Dyclonine inhibited TRPV3 open probability but not the unitary conductance. By molecular simulations and mutagenesis, we further uncovered key residues in TRPV3 pore region that could toggle the inhibitory efficiency of Dyclonine. The functional and mechanistic insights obtained on Dyclonine-TRPV3 interaction will help to conceive therapeutics for skin inflammation.
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therapeutic inhibition of keratinocyte trpv3 sensory channels by local anesthetic Dyclonine
bioRxiv, 2020Co-Authors: Jing Yao, Qiang Liu, Jin Wang, Xin Wei, Conghui Ping, Yue Gao, Chang XieAbstract:The multimodal sensory channel transient receptor potential vanilloid-3 (TRPV3) is expressed in epidermal keratinocytes and implicated in chronic pruritus, allergy, and inflammation-related skin disorders. Gain-of-function mutations of TRPV3 cause hair growth disorders in mice and Olmsted Syndrome in human. We here report that mouse and human TRPV3 channel is selectively targeted by the clinical medication Dyclonine that exerts a potent inhibitory effect. Accordingly, Dyclonine rescued cell death caused by gain-of-function TRPV3 mutations and suppressed pruritus symptoms in vivo in mouse model. At the single-channel level, Dyclonine inhibited TRPV3 open probability but not the unitary conductance. By molecular docking and mutagenesis, we further uncovered single residues in TRPV3 pore region that could toggle the inhibitory efficiency of Dyclonine. The functional and mechanistic insights obtained on Dyclonine-TRPV3 interaction will help to conceive updated therapeutics for skin inflammation.
Yanning Hou - One of the best experts on this subject based on the ideXlab platform.
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development of a hplc ms ms method for simultaneous determination of tinidazole Dyclonine and chlorhexidine in rat plasma and its application in the pharmacokinetic research of a film forming solution
Journal of Pharmaceutical and Biomedical Analysis, 2012Co-Authors: Jianfang Liu, Yunhao Zhang, Yanning HouAbstract:A rapid and sensitive HPLC/MS/MS method was developed and validated for simultaneous determination of tinidazole, Dyclonine and chlorhexidine, the three main components of a film-forming solution, in rat plasma. The plasma samples were pretreated by solid phase extraction (SPE) method. Separation was achieved on a Phenomenex Gemini C(18) column (50 mm × 2.0 mm, 5 μm) using an isocratic mobile phase system composed of methanol-ammonium formate (10 mM)-formic acid (56:44:0.2, v/v/v) (pH 3.5) at a flow rate of 0.2 mL/min. Analytes were determined by tandem mass spectrometry with electrospray positive ionization and multiple-reaction monitoring (MRM) mode. The monitoring ions were (m/z) 247.4 → (m/z) 81.9 for tinidazole, (m/z) 290.1 → (m/z) 97.8 for Dyclonine, (m/z) 505.0 → (m/z) 335.3 for chlorhexidine and (m/z) 282.1 → (m/z) 212.0 for phentolamine (internal standard). The calibration curves were linear in the range of 2-1000 ng/mL for the three components. The precision and accuracy of the method were well within the generally accepted criteria for biomedical analysis. It has been successfully applied to the pharmacokinetic research of a film-forming solution in rat.
