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Cardioprotective effect of ginsenoside Rb1 via regulating metabolomics profiling and AMP-activated protein kinase-dependent mitophagy

  • Hu, Jingui;Zhang, Ling;Fu, Fei;Lai, Qiong;Zhang, Lu;Liu, Tao;Yu, Boyang;Kou, Junping;Li, Fang
    • Journal of Ginseng Research
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    • v.46 no.2
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    • pp.255-265
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    • 2022
  • Background: Ginsenoside Rb1, a bioactive component isolated from the Panax ginseng, acts as a remedy to prevent myocardial injury. However, it is obscure whether the cardioprotective functions of Rb1 are related to the regulation of endogenous metabolites, and its potential molecular mechanism still needs further clarification, especially from a comprehensive metabolomics profiling perspective. Methods: The mice model of acute myocardial ischemia (AMI) and oxygen glucose deprivation (OGD)-induced cardiomyocytes injury were applied to explore the protective effect and mechanism of Rb1. Meanwhile, the comprehensive metabolomics profiling was conducted by high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (HPLC-Q/TOF-MS) and a tandem liquid chromatography and mass spectrometry (LC-MS). Results: Rb1 treatment profoundly reduced the infarct size and attenuated myocardial injury. The metabolic network map of 65 differential endogenous metabolites was constructed and provided a new inspiration for the treatment of AMI by Rb1, which was mainly associated with mitophagy. In vivo and in vitro experiments, Rb1 was found to improve mitochondrial morphology, mitochondrial function and promote mitophagy. Interestingly, the mitophagy inhibitor partly attenuated the cardioprotective effect of Rb1. Additionally, Rb1 markedly facilitated the phosphorylation of AMP-activated protein kinase α (AMPKα), and AMPK inhibition partially weakened the role of Rb1 in promoting mitophagy. Conclusions: Ginsenoside Rb1 protects acute myocardial ischemia injury through promoting mitophagy via AMPKα phosphorylation, which might lay the foundation for the further application of Rb1 in cardiovascular diseases.

Homogenization of Plastic Behavior of Metallic Particle/Epoxy Composite Adhesive for Cold Spray Deposition (저온 분사 공정을 위한 금속입자/에폭시 복합재료 접착제의 소성 거동의 균질화 기법 연구)

  • Yong-Jun Cho;Jae-An Jeon;Kinal Kim;Po-Lun Feng;Steven Nutt;Sang-Eui Lee
    • Composites Research
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    • v.36 no.3
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    • pp.199-204
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    • 2023
  • A combination of a metallic mesh and an adhesive layer of metallic particle/epoxy composite was introduced as an intermediate layer to enhance the adhesion between cold-sprayed particles and fiber-reinforced composites (FRCs). Aluminum was considered for both the metallic particles in the adhesive and the metallic mesh. To predict the mechanical characteristics of the intermediate bond layer under a high strain rate, the properties of the adhesive layer needed to be calculated or measured. Therefore, in this study, the Al particle/epoxy adhesive was homogenized by using a rule of mixture. To verify the homogenization, the penetration depth, and the thickness decrease after the cold spray deposition from the undeformed surface, was monitored with FE analysis and compared with experimental observation. The comparison displayed that the penetration depth was comparable to the diameters of one cold spray particle, and thus the homogenization approach can be reasonable for the prediction of the stress level of particulate polymer composite interlayer under a high strain rate for cold spray processing.

Mountain-cultivated ginseng protects against cognitive impairments in aged GPx-1 knockout mice via activation of Nrf2/ChAT/ERK signaling pathway

  • Bao Trong Nguyen;Eun-Joo Shin;Ji Hoon Jeong;Naveen Sharma;Ngoc Kim Cuong Tran;Yen Nhi Doan Nguyen;Dae-Joong Kim;Myung Bok Wie;Yi Lee;Jae Kyung Byun;Sung Kwon Ko;Seung-Yeol Nah;Hyoung-Chun Kim
    • Journal of Ginseng Research
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    • v.47 no.4
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    • pp.561-571
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    • 2023
  • Background: Escalating evidence shows that ginseng possesses an antiaging potential with cognitive enhancing activity. As mountain cultivated ginseng (MCG) is cultivated without agricultural chemicals, MCG has emerged as a popular herb medicine. However, little is known about the MCG-mediated pharmacological mechanism on brain aging. Methods: As we demonstrated that glutathione peroxidase (GPx) is important for enhancing memory function in the animal model of aging, we investigated the role of MCG as a GPx inducer using GPx-1 (a major type of GPx) knockout (KO) mice. We assessed whether MCG modulates redox and cholinergic parameters, and memory function in aged GPx-1 knockout KOmice. Results: Redox burden of aged GPx-1 KO mice was more evident than that of aged wild-type (WT) mice. Alteration of Nrf2 DNA binding activity appeared to be more evident than that of NFκB DNA binding activity in aged GPx-1 KO mice. Alteration in choline acetyltransferase (ChAT) activity was more evident than that in acetylcholine esterase activity. MCG significantly attenuated reductions in Nrf2 system and ChAT level. MCG significantly enhanced the co-localization of Nrf2-immunoreactivity and ChAT-immunoreactivity in the same cell population. Nrf2 inhibitor brusatol significantly counteracted MCG-mediated up-regulation in ChAT level and ChAT inhibition (by k252a) significantly reduced ERK phosphorylation by MCG, suggesting that MCG might require signal cascade of Nrf2/ChAT/ERK to enhance cognition. Conclusion: GPx-1 depletion might be a prerequisite for cognitive impairment in aged animals. MCG-mediated cognition enhancement might be associated with the activations of Nrf2, ChAT, and ERK signaling cascade.

A Study on the Regional Policy for Promoting the Creation of Technology Based Innovation Firms (기술혁신형 중소기업의 창업환경 조성방안)

  • Lee, J.H.;Bae, B.Y.
    • Korean Business Review
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    • v.21 no.1
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    • pp.91-117
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    • 2008
  • Since the late 20th century, due to the globalization of markets and the rapid developments of information and communication technologies, the world has entered into the age of fierce competition. With their abundant low-cost labor, former communist countries such as China, Russia and East Europe and former low-developed countries such as India and Brazil have received foreign investments from major industrial companies. Thus, there are no other alternatives remained for Korea and OECD countries other than moving the industrial economies to the knowledge based innovation systems. In the knowledge based innovation systems, economic developments and employments of regions and nations depend solely on companies situated in their territories. In this article, after reviewing the current state of technological based innovation small firms in korea, we provide a theoretical framework to promote the level of technology based innovation and entrepreneurship. The theoretical framework for analysis and policy suggestions is based on the Schumpeter's value system model that consist of supply factors, demand factors, and supporting institutions. In order to create more innovative small businesses, we insist on the followings. First, more R&D and innovation activities related with promising new technologies should be performed. Second, more R&D funds for technological innovation small companies should be provided from governments. Third, more M&A transactions and technology transactions should be marketed freely and competitively. Fourth, more business incubating services and venture capital services should be provided. Fifth, entrepreneurship and innovation culture should be popular and institutionized among people.

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A Design on Face Recognition System Based on pRBFNNs by Obtaining Real Time Image (실시간 이미지 획득을 통한 pRBFNNs 기반 얼굴인식 시스템 설계)

  • Oh, Sung-Kwun;Seok, Jin-Wook;Kim, Ki-Sang;Kim, Hyun-Ki
    • Journal of Institute of Control, Robotics and Systems
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    • v.16 no.12
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    • pp.1150-1158
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    • 2010
  • In this study, the Polynomial-based Radial Basis Function Neural Networks is proposed as one of the recognition part of overall face recognition system that consists of two parts such as the preprocessing part and recognition part. The design methodology and procedure of the proposed pRBFNNs are presented to obtain the solution to high-dimensional pattern recognition problem. First, in preprocessing part, we use a CCD camera to obtain a picture frame in real-time. By using histogram equalization method, we can partially enhance the distorted image influenced by natural as well as artificial illumination. We use an AdaBoost algorithm proposed by Viola and Jones, which is exploited for the detection of facial image area between face and non-facial image area. As the feature extraction algorithm, PCA method is used. In this study, the PCA method, which is a feature extraction algorithm, is used to carry out the dimension reduction of facial image area formed by high-dimensional information. Secondly, we use pRBFNNs to identify the ID by recognizing unique pattern of each person. The proposed pRBFNNs architecture consists of three functional modules such as the condition part, the conclusion part, and the inference part as fuzzy rules formed in 'If-then' format. In the condition part of fuzzy rules, input space is partitioned with Fuzzy C-Means clustering. In the conclusion part of rules, the connection weight of pRBFNNs is represented as three kinds of polynomials such as constant, linear, and quadratic. Coefficients of connection weight identified with back-propagation using gradient descent method. The output of pRBFNNs model is obtained by fuzzy inference method in the inference part of fuzzy rules. The essential design parameters (including learning rate, momentum coefficient and fuzzification coefficient) of the networks are optimized by means of the Particle Swarm Optimization. The proposed pRBFNNs are applied to real-time face recognition system and then demonstrated from the viewpoint of output performance and recognition rate.

An investigative study of enrichment reduction impact on the neutron flux in the in-core flux-trap facility of MTR research reactors

  • Xoubi, Ned;Darda, Sharif Abu;Soliman, Abdelfattah Y.;Abulfaraj, Tareq
    • Nuclear Engineering and Technology
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    • v.52 no.3
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    • pp.469-476
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    • 2020
  • Research reactors in-core experimental facilities are designed to provide the highest steady state flux for user's irradiation requirements. However, fuel conversion from highly enriched uranium (HEU) to low enriched uranium (LEU) driven by the ongoing effort to diminish proliferation risk, will impact reactor physics parameters. Preserving the reactor capability to produce the needed flux to perform its intended research functions, determines the conversion feasibility. This study investigates the neutron flux in the central experimental facility of two material test reactors (MTR), the IAEA generic10 MW benchmark reactor and the 22 MW s Egyptian Test and Research Reactor (ETRR-2). A 3D full core model with three uranium enrichment of 93%, 45%, and 20% was constructed utilizing the OpenMC particle transport Monte Carlo code. Neutronics calculations were performed for fresh fuel, the beginning of life cycle (BOL) and end of life cycle (EOL) for each of the three enrichments for both the IAEA 10 MW generic reactor and core 1/98 of the ETRR-2 reactor. Criticality calculations of the effective multiplication factor (Keff) were executed for each of the twelve cases; results show a reasonable agreement with published benchmark values for both reactors. The thermal, epithermal and fast neutron fluxes were tallied across the core, utilizing the mesh tally capability of the code and are presented here. The axial flux in the central experimental facility was tallied at 1 cm intervals, for each of the cases; results for IAEA 10 MW show a maximum reduction of 14.32% in the thermal flux of LEU to that of the HEU, at EOL. The reduction of the thermal flux for fresh fuel was between 5.81% and 9.62%, with an average drop of 8.1%. At the BOL the thermal flux showed a larger reduction range of 6.92%-13.58% with an average drop of 10.73%. Furthermore, the fission reaction rate was calculated, results showed an increase in the peak fission rate of the LEU case compared to the HEU case. Results for the ETRR-2 reactor show an average increase of 62.31% in the thermal flux of LEU to that of the HEU due to the effect of spectrum hardening. The fission rate density increased with enrichment, resulting in 34% maximum increase in the HEU case compared to the LEU case at the assemblies surrounding the flux trap.

Inhibition of HBV replication and gene expression in vitro and in vivo with a single AAV vector delivering two shRNA molecules

  • Li, Zhi;He, Ming-Liang;Yao, Hong;Dong, Qing-Ming;Chen, Yang-Chao;Chan, Chu-Yan;Zheng, Bo-Jian;Yuen, Kwok-Yung;Peng, Ying;Sun, Qiang;Yang, Xiao;Lin, Marie C.;Sung, Joseph J.Y.;Kung, Hsiang-Fu
    • BMB Reports
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    • v.42 no.1
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    • pp.59-64
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    • 2009
  • Hepatitis B virus (HBV) infection is highly prevalent worldwide. The major challenge for current antiviral treatment is the elevated drug resistance that occurs via rapid viral mutagenesis. In this study, we developed AAV vectors to simultaneously deliver two or three shRNAs targeting different HBV-related genes. These vectors showed markedly better antiviral effects than ones that delivered a single shRNA in vitro. A dual shRNA expression vector (AAV-157i/1694i), which simultaneously expressed two shRNAs targeted the S and X genes of HBV, reduced HBsAg, HBeAg and HBV DNA levels by $87{\pm}4$, $80.3{\pm}2.6$ and $86.2{\pm}7%$ respectively, eight days post-transduction. In a mouse model of prophylactic treatment, HBsAg and HBeAg were reduced to undetectable levels and the serum HBV DNA level was reduced by at least 100 fold. These results indicate that AAV-157i/1694i generates potent anti-HBV effects and that the strategy of constructing multi-shRNA expression vectors may lead to enhanced anti-HBV efficacy and overcome the evading mechanism of the virus and thus the development of drug resistance.

Effects of Replacing Lucerne (Medicago sativa L.) Hay with Fresh Citrus Pulp on Ruminal Fermentation and Ewe Performance

  • Sparkes, J.L.;Chaves, A.V.;Fung, Y.T.E.;van Ekris, I.;Bush, R.D.
    • Asian-Australasian Journal of Animal Sciences
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    • v.23 no.2
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    • pp.197-204
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    • 2010
  • Two studies were conducted to determine the effects of replacing 30% (% in diet DM) of lucerne (Medicago sativa L.) hay with citrus pulp in Merino ewe diets: i) an in vitro study which measured ruminal fermentation; and ii) an in vivo study in which twelve Merino ewes pre- and post-lambing were fed experimental diets in a cross-over design over 120 days to evaluate effects on ewe performance (i.e. DM intake, average daily gain (ADG) and wool growth). In both the in vitro and in vivo studies, the control treatment consisted of lucerne (91.3% in diet DM), lupins (8.3% in diet DM) and phosphate (0.42% in diet DM), while the citrus pulp treatment consisted of lucerne (57.7% in diet DM), lupins (9.5% in diet DM), phosphate (0.48% in diet DM) and fresh citrus pulp (32.3% in diet DM). Data were analysed using the mixed model procedure of SAS. In the in vitro study, gas production, total volatile fatty acid (VFA) yield, proportion of propionic acid to total VFA and in vitro dry matter digestibility (IVDMD) were higher (p<0.02) in the citrus pulp treatment compared to the control treatment. In contrast, in vitro ammonia production, pH and the acetate to propionate ratio were lower (p<0.03) for the citrus pulp treatment compared to the control treatment. In the in vivo study, DM intake of ewes fed the citrus pulp diet was lower than their control ewe counterparts throughout both the pre- and post-lambing periods (928.9 vs. 1,115.0 g/d pre-; 1,285.0 vs. 1,620.3 g/d post-lambing, p<0.01), however ADG was similar (p = 0.12). Wool growth parameters and lamb performance did not differ (p>0.32) between treatments. In summary, the in vitro study demonstrated that the replacement of 30% of a lucerne diet with fresh citrus pulp improved total VFA yield, increased total gas production and improved IVDMD, while decreasing the production of ammonia, acetic acid and rumen pH. In addition, the in vivo study demonstrated that the replacement of 30% of a lucerne diet with fresh citrus pulp pre- and post-lambing decreased intake but did not affect ewe performance in terms of ADG and wool growth. These findings, of course, would be of significant interest to sheep producers endeavouring to control cost of feed ingredients whilst maintaining productivity.

Methyl Donor Status Influences DNMT Expression and Global DNA Methylation in Cervical Cancer Cells

  • Poomipark, Natwadee;Flatley, Janet E;Hill, Marilyn H;Mangnall, Barbara;Azar, Elnaz;Grabowski, Peter;Powers, Hilary J
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3213-3222
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    • 2016
  • Background: Methyl donor status influences DNA stability and DNA methylation although little is known about effects on DNA methyltransferases. The aim of this study was to determine whether methyl-donor status influences DNA methyltransferase (Dnmt) gene expression in cervical cancer cells, and if so, whether there are associated effects on global DNA methylation. Materials and Methods: The human cervical cancer cell line, C4-II, was grown in complete medium and medium depleted of folate (F-M+) and folate and methionine (F-M-). Growth rate, intracellular folate, intracellular methionine and homocysteine in the extracellular medium were measured to validate the cancer cell model of methyl donor depletion. Dnmt expression was measured by qRT-PCR using relative quantification and global DNA methylation was measured using a flow cytometric method. Results: Intracellular folate and methionine concentrations were significantly reduced after growth in depleted media. Growth rate was also reduced in response to methyl donor depletion. Extracellular homocysteine was raised compared with controls, indicating disturbance to the methyl cycle. Combined folate and methionine depletion led to a significant down-regulation of Dnmt3a and Dnmt3b; this was associated with an 18% reduction in global DNA methylation compared with controls. Effects of folate and methionine depletion on Dnmt3a and 3b expression were reversed by transferring depleted cells to complete medium. Conclusions: Methyl donor status can evidently influence expression of Dnmts in cervical cancer cells, which is associated with DNA global hypomethylation. Effects on Dnmt expression are reversible, suggesting reversible modulating effects of dietary methyl donor intake on gene expression, which may be relevant for cancer progression.

A Study on the Economic Efficiency of Capital Market (자본시장(資本市場)의 경제적(經濟的) 효율성(效率性)에 관한 연구(硏究))

  • Nam, Soo-Hyun
    • The Korean Journal of Financial Management
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    • v.2 no.1
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    • pp.55-75
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    • 1986
  • This article is to analyse the economic efficiency of capital market, which plays a role of resource allocation in terms of financial claims such as stock and bond. It provides various contributions to the welfare theoretical aspects of modern capital market theory. The key feature that distinguishes the theory described here from traditional welfare theory is the presence of uncertainty. Securities has time dimensions and the state and outcome of the future are really uncertain. This problem resulting from this uncertainty can be solved by complete market, but it has a weak power to explain real stock market. Capital Market is faced with the uncertainity because it is a kind of incomplete market. Individuals and firms in capital market made their consumption-investment decision by their own criteria, i. e. the maximization of expected utility form intertemporal consumption and the maximization of the market value of firm. We noted that allocative decisions that had to be made in the economy could be naturally subdivided into two groups. One set of decisions concerned the allocation of first-period resources among consumption $C_i$, investment in risky firms $I_j$, and riskless investment M. The other decisions concern the distribution among individuals of income available in the second period $Y_i(\theta)$. Corresponing to this grouping, the theoretical analysis of efficiency has also been dichotomized. The optimality of the distribution of output in the second period is distributive efficiency" and the optimality of the allocation of first-period resources is 'the efficiency of investment'. We have found in the distributive efficiency that the conditions for attainability is the same as the conditions for market optimality. The necessary and sufficient conditions for attainability or market optimality is that (1) all utility functions are such that -$\frac{{U_i}^'(Y_i)}{{U_i}^"(Y_i)}={\mu}_i+{\lambda}Y_i$-linear risk tolerance function where the coefficients ${\mu}_i$ and $\lambda$ are independent of $Y_i$, and (2) there are homogeneous expectations, i. e. ${\Large f}_i(\theta)={\Large f}(\theta)$ for every i. On the other hand, the efficiency of investment has disagreement about optimal investment level. The investment level for market rule will not generally lead to Pareto-optimal allocation of investment. This suboptimality is caused by (1)the difference of Diamond's decomposable production function and mean-variance valuation model and (2) the selection of exelusive investment or competitive investment. In conclusion, this article has made an analysis of conditions and processes of Pareto-optimal allocation of resources in capital marker and tried to connect with significant issues in modern finance.

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