Protein target identification of ginsenosides in skeletal muscle tissues: discovery of natural small-molecule activators of muscle-type creatine kinase

Chen, Feiyan,Zhu, Kexuan,Chen, Lin,Ouyang, Liufeng,Chen, Cuihua,Gu, Ling,Jiang, Yucui,Wang, Zhongli,Lin, Zixuan,Zhang, Qiang,Shao, Xiao,Dai, Jianguo,Zhao, Yunan The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.3

Background: Ginseng effectively reduces fatigue in both animal models and clinical trials. However, the mechanism of action is not completely understood, and its molecular targets remain largely unknown. Methods: By screening for proteins that interact with the primary components of ginseng (ginsenosides) in an affinity chromatography assay, we have identified muscle-type creatine kinase (CK-MM) as a potential target in skeletal muscle tissues. Results: Biolayer interferometry analysis showed that ginsenoside metabolites, instead of parent ginsenosides, had direct interaction with recombinant human CK-MM. Subsequently, 20(S)-protopanaxadiol (PPD), which is a ginsenoside metabolite and displayed the strongest interaction with CK-MM in the study, was selected as a representative to confirm direct binding and its biological importance. Biolayer interferometry kinetics analysis and isothermal titration calorimetry assay demonstrated that PPD specifically bound to human CK-MM. Moreover, the mutation of key amino acids predicted by molecular docking decreased the affinity between PPD and CK-MM. The direct binding activated CK-MM activity in vitro and in vivo, which increased the levels of tissue phosphocreatine and strengthened the function of the creatine kinase/phosphocreatine system in skeletal muscle, thus buffering cellular ATP, delaying exercise-induced lactate accumulation, and improving exercise performance in mice. Conclusion: Our results suggest a cellular target and an initiating molecular event by which ginseng reduces fatigue. All these findings indicate PPD as a small molecular activator of CK-MM, which can help in further developing better CK-MM activators based on the dammarane-type triterpenoid structure.

Protein target identifi cation of ginsenosides in skeletal muscle tissues: discovery of natural smallmolecule activators of muscle-type creatine kinase

Feiyan Chen,Kexuan Zhu,Lin Chen,Liufeng Ouyang,Cuihua Chen,Ling Gu,Yucui Jiang,Zhongli Wang,Zixuan Lin,Qiang Zhang,Xiao Shao,Jianguo Dai,Yunan Zhao 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.3

Background: Ginseng effectively reduces fatigue in both animal models and clinical trials. However, themechanism of action is not completely understood, and its molecular targets remain largely unknown. Methods: By screening for proteins that interact with the primary components of ginseng (ginsenosides)in an affinity chromatography assay, we have identified muscle-type creatine kinase (CK-MM) as a potentialtarget in skeletal muscle tissues. Results: Biolayer interferometry analysis showed that ginsenoside metabolites, instead of parent ginsenosides,had direct interaction with recombinant human CK-MM. Subsequently, 20(S)-protopanaxadiol(PPD), which is a ginsenoside metabolite and displayed the strongest interaction with CK-MM in thestudy, was selected as a representative to confirm direct binding and its biological importance. Biolayerinterferometry kinetics analysis and isothermal titration calorimetry assay demonstrated that PPDspecifically bound to human CK-MM. Moreover, the mutation of key amino acids predicted by moleculardocking decreased the affinity between PPD and CK-MM. The direct binding activated CK-MM activityin vitro and in vivo, which increased the levels of tissue phosphocreatine and strengthened the functionof the creatine kinase/phosphocreatine system in skeletal muscle, thus buffering cellular ATP, delayingexercise-induced lactate accumulation, and improving exercise performance in mice. Conclusion: Our results suggest a cellular target and an initiating molecular event by which ginsengreduces fatigue. All these findings indicate PPD as a small molecular activator of CK-MM, which can helpin further developing better CK-MM activators based on the dammarane-type triterpenoid structure.

Effects of High Pressure on pH, Water-binding Capacity and Textural Properties of Pork Muscle Gels Containing Various Levels of Sodium Alginate

Chen, Cong-Gui,Borjigin, Gerelt,Jiang, Shao-Tong,Tadayuki, Nishiumi,Atsushi, Suzuki Asian Australasian Association of Animal Productio 2006 Animal Bioscience Vol.19 No.11

The objective of this study was to investigate the effects of sodium alginate (SA) and pressurization levels on pH, water-binding and textural properties of pork muscle gels (PMG) containing salt. Ground lean pork with 1.0% NaCl and a given amount of SA (0.25, 0.5, 0.75 and 1.0%, respectively), was pressurized to 100, 200 or 300 MPa and subsequently gelled by heating. Results showed that addition of SA into pork muscle enhanced water-holding capacity (WHC) of PMG (p<0.05) as SA increased from 0.25% to 1.0%, with pH slightly increased (p>0.05). A decrease (p<0.05) was observed in all textural parameters (hardness, cohesiveness, springiness and chewiness). Pressurization had no effect on the tendency of WHC to increase or the decrease of the textural parameters. However, the effectiveness of pressurization to enhance textural properties of PMG was significant at some SA levels, especially ${\geq}200MPa$ and at ${\leq}0.75%$ SA levels. Different combinations of pressure and SA levels could bring about variation in textural properties of PMG while SA enhanced WHC of pork muscle. The multiformity of the texture will open up a wide range of technological possibilities for the manufacture of pork-based restructured low-fat products.

Relationships of uPA and VEGF Expression in Esophageal Cancer and Microvascular Density with Tumorous Invasion and Metastasis

Jiang, Jian-Tao,Zhang, Lan-Fang,Zhou, Bin,Zhang, Shun-Qun,Li, Shao-Min,Zhang, Wei,Zhang, Jin,Qiao, Zhe,Kong, Ran-Ran,Ma, Yue-Feng,Chen, Sheng Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

Objective: To investigate uPA and VEGF expression in esophageal cancer and relations with tumorous invasion and metastasis. Methods: Immunohistochemistry was used to detect uPA and VEGF expression in the normal epithelial tissue of esophageal mucosa and cancer tissue and detect CD34 labeled micrangium and analyze the relationships with clinical pathological features and tumor angiogenesis. Results: Positive rates for uPA and VEGF protein expression were significantly greater in esophageal cancer than normal epithelial tissue (P < 0.05), the two being linked (P <0.05). In addition, uPA and VEGF protein expression of the high microvessel density (MVD) group was significantly lower than in the low MVD group (P < 0.05), with relation to clinical pathological staging, differentiation and lymph node metastasis (P < 0.05). Conclusion: In esophageal cancer tissue, uPA and VEGF proteins are overexpressed and promote tumor angiogenesis, indicative of a poor prognosis.

A Fibrin Matrix Promotes the Differentiation of EMSCs Isolated from Nasal Respiratory Mucosa to Myelinating Phenotypical Schwann-Like Cells

Chen, Qian,Zhang, Zhijian,Liu, Jinbo,He, Qinghua,Zhou, Yuepeng,Shao, Genbao,Sun, Xianglan,Cao, Xudong,Gong, Aihua,Jiang, Ping Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.3

Because Schwann cells perform the triple tasks of myelination, axon guidance and neurotrophin synthesis, they are candidates for cell transplantation that might cure some types of nervous-system degenerative diseases or injuries. However, Schwann cells are difficult to obtain. As another option, ectomesenchymal stem cells (EMSCs) can be easily harvested from the nasal respiratory mucosa. Whether fibrin, an important transplantation vehicle, can improve the differentiation of EMSCs into Schwann-like cells (SLCs) deserves further research. EMSCs were isolated from rat nasal respiratory mucosa and were purified using anti-CD133 magnetic cell sorting. The purified cells strongly expressed HNK-1, nestin, $p75^{NTR}$, S-100, and vimentin. Using nuclear staining, the MTT assay and Western blotting analysis of the expression of cell-cycle markers, the proliferation rate of EMSCs on a fibrin matrix was found to be significantly higher than that of cells grown on a plastic surface but insignificantly lower than that of cells grown on fibronectin. Additionally, the EMSCs grown on the fibrin matrix expressed myelination-related molecules, including myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and galactocerebrosides (GalCer), more strongly than did those grown on fibronectin or a plastic surface. Furthermore, the EMSCs grown on the fibrin matrix synthesized more neurotrophins compared with those grown on fibronectin or a plastic surface. The expression level of integrin in EMSCs grown on fibrin was similar to that of cells grown on fibronectin but was higher than that of cells grown on a plastic surface. These results demonstrated that fibrin not only promoted EMSC proliferation but also the differentiation of EMSCs into the SLCs. Our findings suggested that fibrin has great promise as a cell transplantation vehicle for the treatment of some types of nervous system diseases or injuries.

Structure-based design, structure–activity relationship analysis, and antitumor activity of diaryl ether derivatives

Shao-Mei Yang,Fu-Nan Li,Zhi-Ning Huang,Zhong-Shi Zhou,Jin Hou,Man-Yi Zheng,Li-Juan Wang,Yu Jiang,Xin-Yi Zhou,Qiu-Yue Chen,Shan-Hua Li 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.10

To identify novel therapeutic agents to treatcancer, we synthesized a series of diaryl ether derivatives. Structure–activity relationship studies revealed that thepresence of a chlorine or hydroxyl at the para-position onthe phenyl ring (5h or 5k) significantly enhanced antitumoractivity. Compound 5h had stronger growth inhibitory activityin HepG2, A549, and HT-29 cells than compound 5k,with IC50 values of 2.57, 5.48, and 30.04 lM, respectively. Compound 5h also inhibited the growth of other cells lines,including Hep3B, PLC/PRF5, SMMC-7721, HeLa, andA375, with IC50 values of 2.76, 4.26, 29.66, 18.86, and10.21 lM, respectively. The antitumor activity of compound5h was confirmed by a colony forming assay. Further,our results indicated that the antitumor activity ofcompound 5h may be mediated by enhancing expression ofp21 and cl-caspase3, and leading to apoptosis of cancercells.

MULTISCALE HYDRODYNAMIC JOURNAL BEARING WITH ULTRA LOW SURFACE SEPARATION

Shaojin Shao,Yongbin Zhang,Long Chen,Xuedong Jiang 한국자동차공학회 2022 International journal of automotive technology Vol.23 No.6

When the hydrodynamic journal bearing works under excessively heavy loads, there will be the mixed hydrodynamic regime. In the local area, due to the ultra low surface separation, there is only the physically adsorbed boundary layer lubrication; in the other areas, the hydrodynamic is multiscale contributed by both the adsorbed boundary layer non-continuum flows and the intermediate continuum fluid flow. The present study first gives different governing equations respectively for different flow regimes, and then derives the film pressure and carried load of the bearing. The calculations show that in the condition of ultra low surface clearances, the boundary adsorbed layer effect normally very significantly increases the film pressure and the load-carrying capacity of the bearing, and this increase can be more than 3 orders when the fluid-bearing surface interaction is strong.

Thermo-Mechanical Behavior of Long-Bored Energy Pile: A Full-Scale Field Investigation

Gang Jiang,Dong Shao,Chenfeng Zong,Gen Chen,Jie Huang,Cheng Lin,Xudong Wang,Yuwei Zhang 대한토목학회 2023 KSCE Journal of Civil Engineering Vol.27 No.1

A geothermal energy pile is a revolutionary piling technique that combines a pile foundation with a ground source heat pump system that not only supports the structure but also provides heating and cooling for buildings and bridges. The thermo-mechanical behavior of long energy piles in soft clay has rarely been investigated, despite their increasing utilization. A long floating energy pile with a length-to-diameter ratio of 66.7 was evaluated on its own and monitored in service of the supported structure in the city of Kunshan, China. With vertical mechanical loads, the experiment involved alternate cooling and heating cycles, allowing for careful analysis and assessment of the pile's temperature, stress, and displacement. Temperature-induced stress, axial force, and friction resistance of the pile shaft, as well as the change in displacement of the energy pile throughout building, were all studied. The field observations revealed without any surprise that a longer energy pile outperformed a shorter one in terms of heating exchange capacity with a more homogenous temperature distribution along the pile. Following a quasi-linear relationship with the temperature variation, the thermo-induced additional axial force soared with the larger length-diameter ratio of the pile and may even reach four times that of the pile under pure mechanical loads. Important additional settlements were also observed especially in cooling conditions. The shaft frictions along the long bored energy pile were found to have a complicated distribution, which requires further investigations.

Designing Co7Fe3@TiO2 Core–Shell Nanospheres for Electromagnetic Wave Absorption in S and C Bands

Na Chen,Jian‑Tang Jiang,Zhen‑Jie Guan,Shao‑Jiu Yan,Liang Zhen,Cheng‑Yan Xu 대한금속·재료학회 2020 ELECTRONIC MATERIALS LETTERS Vol.16 No.5

Ferromagnetic-dielectric nanocomposites have attracted extensive interests for its high electromagnetic wave absorption(EMA) performance due to the synergetic effects between different components. Herein, we report the design of core–shellstructured Co7Fe3@TiO2 composite particles, which are subsequently annealed in H2/Ar atmosphere to further improve itsEMA performance. The introducing of TiO2dielectric shell together with hydrogen annealing contributes greatly to theelectromagnetic properties due to the increased conductivity and enhanced ferromagnetic resonance. Excellent EMA performanceis achieved in S (2–4 GHz) and C (4–8 GHz) bands in coatings using Co7Fe3@TiO2 as absorbents. Apart from thehigh EMA efficiency, the location of EMA band can be tailored in a wide range through regulating the coating thickness. Specifically, an effective absorption band of 2.0 GHz in C band at a thickness of 2.62 mm, and an effective absorption bandof 1.7 GHz are achieved in S band at thicknesses of 4.0–5.0 mm. The excellent electromagnetic properties are ascribed tothe effective complementary between dielectric loss and ferromagnetic loss.

Development and evaluation of self-microemulsifying liquid and granule formulations of Brucea javanica oil

Ali Shao,Gang Chen,Nan Jiang,Ye Li,Xiao Zhang,Lu Wen,Fan Yang,Shaoyang Wei 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.8

The aim of this study was to develop andcharacterize a self-microemulsifying drug delivery system(SMEDDS) of Brucea javanica oil (BJO) and transform theliquid formulation into solid granules. Solubility studies ofBJO and pseudo-ternary phase diagrams were used toidentify the most efficient self-emulsification region. Amethyl thiazolyl tetrazolium (MTT) assay was performedto identify cell apoptosis. Antitumor activity studies werealso employed to evaluate the BJO SMEDDS. The optimizedBJO SMEDDS in liquid and granule formulationsrapidly formed fine oil-in-water microemulsions with particlesizes\50 nm. Additionally, the MTT assay demonstratedthat BJO SMEDDS had a significant effect oncancer cells, and antitumor activity studies showedremarkable inhibition of S180 tumors. The BJO SMEDDS,optimized to have good characteristics, was successfullytransformed into solid granules by adsorbing onto crospovidone. The studies of the release of the BJO SMEDDS ofliquid and granules in vitro suggested that the release ofBJO was enhanced by the SMEDDS. These studiesrevealed that the new self-microemulsifying systems ofliquid and granule forms might be promising strategies forthe oral delivery of the poorly water-soluble drug BJO.