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202 results on '"Zhang, Kehong"'

5. Single-cell transcriptome reveals highly complement activated microglia cells in association with pediatric tuberculous meningitis

Author

Mo, Siwei, primary, Shi, Chenyan, additional, Cai, Yi, additional, Xu, Maozhu, additional, Xu, Hongmei, additional, Xu, Yuzhong, additional, Zhang, Kehong, additional, Zhang, Yue, additional, Liu, Jiao, additional, Che, Siyi, additional, Liu, Xiangyu, additional, Xing, Chaonan, additional, Long, Xiaoru, additional, Chen, Xinchun, additional, and Liu, Enmei, additional

Published
2024
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6. Dynamics of polymer translocation into an anisotropic confinement

Author

Zhang, Kehong and Luo, Kaifu

Subjects
Condensed Matter - Soft Condensed Matter, Condensed Matter - Statistical Mechanics, Physics - Biological Physics, Quantitative Biology - Biomolecules
Abstract

Using Langevin dynamics simulations, we investigate the dynamics of a flexible polymer translocation into a confined area under a driving force through a nanopore. We choose an ellipsoidal shape for the confinement and consider the dependence of the asymmetry of the ellipsoid measured by the aspect ratio on the translocation time. Compared with an isotropic confinement (sphere), an anisotropic confinement (ellipsoid) with the same volume slows down the translocation, and the translocation time increases with increasing the aspect ratio of the ellipsoid. We further find that it takes different time for polymer translocation into the same ellipsoid through major-axis and minor-axis directions, depending on the average density of the whole chain in the ellipsoid, $\phi$. For $\phi$ lower than a critical value $\phi_c$, the translocation through minor axis is faster, and vice versa. These complicated behaviors are interpreted by the degree of the confinement and anisotropic confinement induced folding of the translocated chain., Comment: 8 pages, 7 figures, accepted to Soft Matter

Published
2012

7. Dynamics of polymer translocation into a circular nanocontainer through a nanopore

Author

Zhang, Kehong and Luo, Kaifu

Subjects
Condensed Matter - Soft Condensed Matter, Physics - Biological Physics, Quantitative Biology - Biomolecules
Abstract

Using Langevin dynamics simulations, we investigate the dynamics of polymer translocation into a circular nanocontainer through a nanopore under a driving force $F$. We observe that the translocation probability initially increases and then saturates with increasing $F$, independent of $\phi$, which is the average density of the whole chain in the nanocontainer. The translocation time distribution undergoes a transition from a Gaussian distribution to an asymmetric distribution with increasing $\phi$. Moreover, we find a nonuniversal scaling exponent of the translocation time as chain length, depending on $\phi$ and $F$. These results are interpreted by the conformation of the translocated chain in the nanocontainer and the time of an individual segment passing through the pore during translocation., Comment: 9 pages, 12 figures

Published
2012
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20. Modulation of Inflammation-Related Lipid Mediator Pathways by Celastrol During Human Macrophage Polarization

Author

Zhang,Kehong, Jordan,Paul Mike, Pace,Simona, Hofstetter,Robert K, Werner,Markus, Chen,Xinchun, Werz,Oliver, Zhang,Kehong, Jordan,Paul Mike, Pace,Simona, Hofstetter,Robert K, Werner,Markus, Chen,Xinchun, and Werz,Oliver

Abstract

Kehong Zhang,1,2 Paul Mike Jordan,1 Simona Pace,1 Robert K Hofstetter,1 Markus Werner,1 Xinchun Chen,2 Oliver Werz1 1Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, Jena, D-07743, Germany; 2Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen, 518000, People’s Republic of ChinaCorrespondence: Oliver Werz, Email oliver.werz@uni-jena.deBackground and Purpose: Celastrol (CS) is a major active ingredient of the Chinese/Asian herb Tripterygium wilfordii that is frequently used as phytomedicine to treat inflammation and autoimmune diseases. We showed before that short-term exposure to CS (1 μM) favorably impacts the biosynthesis of inflammation-related lipid mediators (LM) in human polarized macrophages by modulating the activities of different lipoxygenases (LOXs). However, whether CS regulates the expression of LOXs and other related LM-biosynthetic enzymes during macrophage polarization is unknown. Here, we investigated how CS affects LM-biosynthetic enzyme expression on the protein level and studied concomitant LM signature profiles during polarization of human monocyte-derived macrophages (MDM) towards M1- and M2-like phenotypes.Methods and Results: We used LM metabololipidomics to study the long-term effects of CS on LM profile signatures after manipulation of human monocyte-derived macrophages (MDM) during polarization. Exposure of MDM to low concentrations of CS (ie, 0.2 μM) during polarization to an inflammatory M1 phenotype potently suppressed the formation of pro-inflammatory cyclooxygenase (COX)- and 5-LOX-derived LM, especially prostaglandin (PG)E2. Notably, gene and enzyme expression of COX-2 and microsomal PGE2 synthase (mPGES)-1 as well as M1 markers were strongly decreased by CS during M1-MDM polarization, along with impaired activation of nuclear factor-κB and p38

Published
2022

21. Mycobacterium tuberculosis-Induced Upregulation of the COX-2/mPGES-1 Pathway in Human Macrophages Is Abrogated by Sulfasalazine

Author

Wang, Wenfei, primary, Ning, Yuping, additional, Wang, Yejun, additional, Deng, Guofang, additional, Pace, Simona, additional, Barth, Stefanie A., additional, Menge, Christian, additional, Zhang, Kehong, additional, Dai, Youchao, additional, Cai, Yi, additional, Chen, Xinchun, additional, and Werz, Oliver, additional

Published
2022
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27. Anti-inflammatory celastrol promotes a switch from leukotriene biosynthesis to formation of specialized pro-resolving lipid mediators

Author

Pace, Simona, primary, Zhang, Kehong, additional, Jordan, Paul M., additional, Bilancia, Rossella, additional, Wang, Wenfei, additional, Börner, Friedemann, additional, Hofstetter, Robert K., additional, Potenza, Marianna, additional, Kretzer, Christian, additional, Gerstmeier, Jana, additional, Fischer, Dagmar, additional, Lorkowski, Stefan, additional, Gilbert, Nathaniel C., additional, Newcomer, Marcia E., additional, Rossi, Antonietta, additional, Chen, Xinchun, additional, and Werz, Oliver, additional

Published
2021
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38. Flunarizine suppresses Mycobacterium tuberculosis growth via calmodulin‐dependent phagosome maturation.

Author

Mo, Siwei, Liu, Xiaoqian, Zhang, Kehong, Wang, Wenfei, Cai, Yi, Ouyang, Qi, Zhu, Chuanzhi, Lin, Dachuan, Wan, Haoqiang, Li, Dechang, Wen, Zhihua, and Chen, Xinchun

Subjects
MYCOBACTERIUM tuberculosis, CALMODULIN, BACTERIAL diseases, COMMUNICABLE diseases, PROTEIN kinases, TUBERCULOSIS, CAUSES of death, RIFAMPIN
Abstract

Tuberculosis (TB), an infectious bacterial disease caused by Mycobacterium tuberculosis (Mtb), is a major cause of death worldwide. Multidrug‐resistant TB remains a public health crisis and thus novel effective treatments, such as host‐directed therapies (HDTs), are urgently required to overcome the challenges of TB infection. In this study, we evaluated 4 calcium modulators for their effects on Mtb growth in macrophages. Only flunarizine enhanced the bactericidal ability of macrophages against Mtb, which was induced by an increase in phosphorylated calcium/calmodulin (CaM)‐dependent protein kinase II (pCaMKII) levels. We further discovered that the expression of CaM was decreased in Mtb‐infected macrophages and restored following flunarizine treatment; this was associated with phagolysosome maturation and acidification. Consistent with these findings, the anti‐TB ability of macrophages was reduced following the silencing of CaM or inhibition of CAMKII activity. In conclusion, our results demonstrated that flunarizine enhanced the bactericidal ability of macrophages and clarified its CaM–pCAMKII‐dependent mechanism. Therefore, our findings strongly support further studies of this currently approved drug as an HDT candidate for TB therapy. [ABSTRACT FROM AUTHOR]

Published
2022
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44. Flunarizine suppresses Mycobacterium tuberculosisgrowth via calmodulin‐dependent phagosome maturation

Author

Mo, Siwei, Liu, Xiaoqian, Zhang, Kehong, Wang, Wenfei, Cai, Yi, Ouyang, Qi, Zhu, Chuanzhi, Lin, Dachuan, Wan, Haoqiang, Li, Dechang, Wen, Zhihua, and Chen, Xinchun

Abstract

Tuberculosis (TB), an infectious bacterial disease caused by Mycobacterium tuberculosis(Mtb), is a major cause of death worldwide. Multidrug‐resistant TB remains a public health crisis and thus novel effective treatments, such as host‐directed therapies (HDTs), are urgently required to overcome the challenges of TB infection. In this study, we evaluated 4 calcium modulators for their effects on Mtbgrowth in macrophages. Only flunarizine enhanced the bactericidal ability of macrophages against Mtb, which was induced by an increase in phosphorylated calcium/calmodulin (CaM)‐dependent protein kinase II (pCaMKII) levels. We further discovered that the expression of CaM was decreased in Mtb‐infected macrophages and restored following flunarizine treatment; this was associated with phagolysosome maturation and acidification. Consistent with these findings, the anti‐TB ability of macrophages was reduced following the silencing of CaM or inhibition of CAMKII activity. In conclusion, our results demonstrated that flunarizine enhanced the bactericidal ability of macrophages and clarified its CaM–pCAMKII‐dependent mechanism. Therefore, our findings strongly support further studies of this currently approved drug as an HDT candidate for TB therapy. Flunarizine limits Mycobacterium tuberculosis growth in macrophages by promoting CaM‐pCAMKII‐mediated phagolysosome maturation.

Published
2022
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48. Single dose of morphine produced a prolonged effect on dopamine neuron activities

Author

Zhang Kehong, Jin Guo-zhang, Zhang Hai, Zhang Die, and Zhen Xuechu

Subjects
Pathology, RB1-214
Abstract

Abstract Background Clinical observation and experimental studies have indicated that a single exposure to morphine could induce tolerance and dependence. It has become a concern in clinical antinociceptive practice. However, the underling mechanism remains unknown. This study was designed to explore the changes of dopamine (DA) neuron activities in the ventral tegmental area (VTA) by employing a spectral analysis followed single morphine treatment. Results Acute morphine treatment significantly increased not only the firing rate and firing population but also the power of slow oscillation of DA neurons in naïve rats. These changes lasted at least for 3 days following the morphine treatment. During this period of time, responses of the DA neurons to subsequent morphine challenge were diminished. We further demonstrated a transient desensitization of opiate receptors as monitored by GTPγS binding to G-proteins. The present study provided first direct evidence for the temporal changes in the VTA DA neuron activities and opiate receptors desensitization. Conclusion Prolonged VTA DA neuron activation and opiate receptors desensitization followed single morphine exposure may underlie the development of dependence and tolerance that may associate with the acute analgesic tolerance and acute addiction of morphine.

Published
2008
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