• Title/Summary/Keyword: Mechanistic study

Search Result 298, Processing Time 0.031 seconds

Echinacoside Induces UCP1- and ATP-Dependent Thermogenesis in Beige Adipocytes via the Activation of Dopaminergic Receptors

  • Kiros Haddish;Jong Won Yun
    • Journal of Microbiology and Biotechnology
    • /
    • v.33 no.10
    • /
    • pp.1268-1280
    • /
    • 2023
  • Echinacoside (ECH) is a naturally occurring phenylethanoid glycoside, isolated from Echinacea angustifolia, and this study aimed to analyze its effect on thermogenesis and its interaction with dopaminergic receptors 1 and 5 (DRD1 and DRD5) in 3T3-L1 white adipocytes and mice models. We employed RT-PCR, immunoblot, immunofluorescence, a staining method, and an assay kit to determine its impact. ECH showed a substantial increase in browning signals in vitro and a decrease in adipogenic signals in vivo. Additionally, analysis of the iWAT showed that the key genes involved in beiging, mitochondrial biogenesis, and ATP-dependent thermogenesis were upregulated while adipogenesis and lipogenesis genes were downregulated. OXPHOS complexes, Ca2+ signaling proteins as well as intracellular Ca2+ levelswere also upregulated in 3T3-L1 adipocytes following ECH treatment. This was collectively explained by mechanistic studies which showed that ECH mediated the beiging process via the DRD1/5-cAMP-PKA and subsequent downstream molecules, whereas it co-mediated the α1-AR-signaling thermogenesis via the DRD1/5/SERCA2b/RyR2/CKmt pathway in 3T3-L1 adipocytes. Animal experiments revealed that there was a 12.28% reduction in body weight gain after the ECH treatment for six weeks. The effects of ECH treatment on adipose tissue can offer more insights into the treatment of obesity and metabolic syndrome.

Phytochemical Identification of Bioactive Constituents of Dendrobii herba (생약석곡(Dendrobii herba)의 생리활성 성분 규명)

  • Bomi Nam
    • Proceedings of the Plant Resources Society of Korea Conference
    • /
    • 2023.04a
    • /
    • pp.18-18
    • /
    • 2023
  • Two new phenanthrenes, namely, (1R,2R)-1,7-hydroxy-2,8-methoxy-2,3-dihydrophenanthrene-4(1H)-one (1) and 2,7-dihydroxyphenanthrene-1,4-dione (2), were isolated from the ethyl acetate-soluble fraction of Dendrobii Herba, together with the eleven known compounds, densiflorol B (3), 6,7-dimethoxyphenanthrene2,5-diol (4), dehydroorchinol (5), 1,5,7-trimethoxy-2-phenanthrenol (6), denthyrsinin (7), ephemerantol A (8), lusianthridin (9), moscatilin (10), gigantol (11), 3-[(1E)-2-(3-hydroxyphenyl)ethenyl]-5-methoxyphenol (12) and (-)-syringaresinol (13). Structures of 1 and 2 were elucidated by analyzing 1D and 2D NMR as well as HR-ESI-MS data. The absolute configuration of compound 1 was confirmed by ECD spectroscopic method. In cytotoxicity evaluation using FaDu human hypopharyngeal squamous carcinoma cell line, compounds 3-6, 8, 10 and 12 showed activities, with IC50 values ranging from 2.55 to 17.70 μM. Among them, compound 10 exhibited remarkable cytotoxic activity with IC50 value of 2.55 μM. This is the first report on the anticancer mechanistic study of compound 10 in HNSCC including FaDu cells.

  • PDF

Comprehensive Analysis of the Corrosion Inhibition Performance of 4-Piperonylideneaminoantipyrine for Mild Steel in HCl Solution: Concentration, Time, Temperature Effects, and Mechanistic Insights

  • Ahmed Y. I. Rubaye;Sabah M. Beden;Ahmed A. Alamiery;A. A. H. Kadhum;Waleed K. Al-Azzawi
    • Corrosion Science and Technology
    • /
    • v.23 no.1
    • /
    • pp.20-32
    • /
    • 2024
  • Metal corrosion in acidic environments is a major issue in various industrial applications. This study evaluates the 4-piperonylideneaminoantipyrine (PPDAA) corrosion inhibition efficiency for mild steel in a hydrochloric acid (HCl) solution. The weight loss method was used to determine the corrosion inhibition efficiency at different concentrations and immersion time periods. Results revealed that the highest inhibition efficiency (94.3%) was achieved at 5 mM concentration after 5 hours of immersion time. To inspect the surface morphology of the inhibitor film on the mild steel surface, scanning electron microscopy (SEM) was used before and after immersion in 1.0 M HCl. Density functional theory (DFT) calculations were performed to investigate the molecular structure and electronic properties of the inhibitor molecule to understand the corrosion inhibition mechanism. Theoretical results showed that the inhibitor molecule can adsorb onto the mild steel surface through its nitrogen and oxygen atoms, forming a protective layer that prevents HCl corrosive attack. These findings highlight the potential of PPDAA as an effective corrosion inhibitor for mild steel in HCl solution. Moreover, combining experimental and theoretical approaches provides insights into the mechanism of corrosion inhibition, which is essential for developing effective strategies to prevent metal corrosion in acidic environments.

Development of FEMAXI-ATF for analyzing PCMI behavior of SiC cladded fuel under power ramp conditions

  • Yoshihiro Kubo;Akifumi Yamaji
    • Nuclear Engineering and Technology
    • /
    • v.56 no.3
    • /
    • pp.846-854
    • /
    • 2024
  • FEMAXI-ATF is being developed for fuel performance modeling of SiC cladded UO2 fuel with focuses on modeling pellet-cladding mechanical interactions (PCMI). The code considers probability distributions of mechanical strengths of monolithic SiC (mSiC) and SiC fiber reinforced SiC matrix composite (SiC/SiC), while it models pseudo-ductility of SiC/SiC and propagation of cladding failures across the wall thickness direction in deterministic manner without explicitly modeling cracks based on finite element method in one-dimensional geometry. Some hypothetical BWR power ramp conditions were used to test sensitivities of different model parameters on the analyzed PCMI behavior. The results showed that propagation of the cladding failure could be modeled by appropriately reducing modulus of elasticities of the failed wall element, so that the mechanical load of the failed element could be re-distributed to other intact elements. The probability threshold for determination of the wall element failure did not have large influence on the predicted power at failure when the threshold was varied between 25 % and 75 %. The current study is still limited with respect to mechanistic modeling of SiC failure as it only models the propagation of the cladding wall element failure across the homogeneous continuum wall without considering generations and propagations of cracks.

Development of a Zebrafish Larvae Model for Diabetic Heart Failure With Reduced Ejection Fraction

  • Inho Kim;Seung Hyeok Seok;Hae-Young Lee
    • Korean Circulation Journal
    • /
    • v.53 no.1
    • /
    • pp.34-46
    • /
    • 2023
  • Background and Objectives: Diabetes mellitus (DM)-associated heart failure (HF) causes high morbidity and mortality. In this study, we established a zebrafish larvae model for in vivo research on diabetic HF. Methods: DM-like phenotypes were induced by treating zebrafish larvae with a combination of D-glucose (GLU) and streptozotocin (STZ). HF was induced by treatment with terfenadine (TER), a potassium channel blocker. Additionally, myocardial contractility, motility, and viability were evaluated. Results: The zebrafish larvae treated with a combination of GLU and STZ showed significantly higher whole-body glucose concentrations, lower insulin levels, and higher phosphoenolpyruvate carboxykinase levels, which are markers of abnormal glucose homeostasis, than the group treated with only GLU, with no effect on viability. When treated with TER, DM zebrafish showed significantly less myocardial fractional shortening and more irregular contractions than the non-DM zebrafish. Furthermore, in DM-HF with reduced ejection fraction (rEF) zebrafish, a significant increase in the levels of natriuretic peptide B, a HF biomarker, markedly reduced motility, and reduced survival rates were observed. Conclusions: We established a DM-HFrEF zebrafish model by sequentially treating zebrafish larvae with GLU, STZ, and TER. Our findings indicate the potential utility of the developed zebrafish larvae model not only in screening studies of new drug candidates for DM-HFrEF but also in mechanistic studies to understand the pathophysiology of DM-HFrEF.

Study on Mechanistic Pattern Identification of Disease for NaeGyungPyen of DongEuiBoGam ("동의보감(東醫寶鑑)" 내경편(內景編)에 나타난 질병(疾病)의 병기론적(病機論的) 변증(辨證)화 연구 - 정신기혈(精神氣血)을 중심으로 -)

  • Kim, Yeong-Mok
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.24 no.2
    • /
    • pp.177-186
    • /
    • 2010
  • This study is about researching DongEuiBoGam by analysing with pattern identification of modern Traditional Korean medical patholgy as more logical, systematic and standardized theory. Disease pattern mechanisms of essence, spirit, qi and blood in NaeGyungPyeb of DongEuiBoGam are these. In Essence, this explain mechanism of disease patterns those are seminal emission, dream emission, spermatorrhea, white ooze. These disease pattern's mechanisms are kidney yang deficiency, kidney yin deficiency, heart yang deficiency, heart yin deficiency, heart qi deficiency, spleen qi deficiency and so on. On viewpoints of viscera and bowels they are related with heart, kidney, spleen. And most of them are deficiency from deficiency-excess Pattern Identification. Classifying disease pattern of qi is about upward, downward movement and more concentrated deficiency than excess pattern. Fright palpitations can be classified heart deficiency with timidity, heart blood and qi deficiency, heart qi deficiency, heart blood deficiency, heart qi movement stagnation, water qi intimidating the heart, phlegm-fire harassing the heart, phlegm clouding the pericardium, and so on. Palpitations can be classified heart blood deficiency, heart yin deficiency, heart deficiency with timidity, heart spleen blood deficiency, spleen qi deficiency, phlegm-fire harassing the heart, intense heart fire, and so on. Forgetfulness can be classified heart spleen blood deficiency, heart spleen qi deficiency, kidney essence deficiency, heart qi deficiency, non-interaction between the heart and kidney, etc. for deficiency pattern, phlegm clouding the pericardium for excess pattern. In Blood just say inside bleeding pattern's category, there are nose bleeding, flopping syncope, qi counterflow, blood vomiting, hemoptysis, spitting of blood, bloody stool, hematuria, and so on. Like these, this study identify pattern of disease in DongEuiBoGam by mechanism of disease theory.

Cholangiocarcinogenesis Following Oval Cell Induction and Clonorchis sinensis Infestation in Hamster (햄스터 oval cell의 간흡충감염 후 담관암으로의 분화에 관한 세포병리학적 연구)

  • Yoon, Byung-Il;Kim, Bang-Hyun;Kim, Dae-Yong
    • Korean Journal of Veterinary Pathology
    • /
    • v.6 no.1
    • /
    • pp.41-48
    • /
    • 2002
  • Oval cell is considered as facultative precursor cells for both hepatocytes and biliary cells, as well as origin of hepatocellar and cholangiocellular carcinoma (CCC) during carcinogenesis or toxic liver injury. To clarify the cellular origin or differentiation of cholagiocarcinogensis, the fate of carcinogen-induced oval cells was pathologically and phenotypically chased in Syrian golden hamster liver after Clonorchis sinensis (CS) infection which would give rise to a promoting effect. Two week treatment of hamsters with 0.005% diethylnitrosamine (DEN) followed by 2 week treatment of 1% 2-acetylaminofluorene (AAF) under choline deficient diet resulted in massive proliferation of BrdU labeleed and PCNA positive oval cells showing various distinct morphology, histochemical and immunohistochemical phenotypes for GGT, cytokeratin 19 and OV-6. Oval cells also frequently form ductular-like structures or phenotypically show hepatocyte-like characteristics. After CS infection, the oval cells showed sequential morphological changes to atypicl proliferating bile ductules and all hamsters thereafter developed well differentiated and anaplastic CCC at 16 week after CS infection. In electron microscopy, some bile ductules were constructed by intermediate oval cells and bile ductular cells surrounded by basement membrane. The results of this study strongly suggest that CCC developed in the present study were originated from hepatic stem-like oval cells, supporting the theory of stem cell origin of cancers. In addition, this hamster model would be valuable for the molecular mechanistic study during chemical-triggered cholangiocarcinogenesis.

  • PDF

PRR11 and SKA2 gene pair is overexpressed and regulated by p53 in breast cancer

  • Wang, Yitao;Zhang, Chunxue;Mai, Li;Niu, Yulong;Wang, Yingxiong;Bu, Youquan
    • BMB Reports
    • /
    • v.52 no.2
    • /
    • pp.157-162
    • /
    • 2019
  • Our previous study found that two novel cancer-related genes, PRR11 and SKA2, constituted a classic gene pair that was regulated by p53 and NF-Y in lung cancer. However, their role and regulatory mechanism in breast cancer remain elusive. In this study, we found that the expression levels of PRR11 and SKA2 were upregulated and have a negative prognotic value in breast cancer. Loss-of-function experiments showed that RNAi-mediated knockdown of PRR11 and/or SKA2 inhibited proliferation, migration, and invasion of breast cancer cells. Mechanistic experiments revealed that knockdown of PRR11 and/or SKA2 caused dysregulation of several downstream genes, including CDK6, TPM3, and USP12, etc. Luciferase reporter assays demonstrated that wild type p53 significantly repressed the PRR11-SKA2 bidirectional promoter activity, but not NF-Y. Interestingly, NF-Y was only essential for and correlated with the expression of PRR11, but not SKA2. Consistently, adriamycin-induced (ADR) activation of endogenous p53 also caused significant repression of the PRR11 and SKA2 gene pair expression. Notably, breast cancer patients with lower expression levels of either PRR11 or SKA2, along with wild type p53, exhibited better disease-free survival compared to others with p53 mutations and/or higher expression levels of either PRR11 or SKA2. Collectively, our study indicates that the PRR11 and SKA2 transcription unit might be an oncogenic contributor and might serve as a novel diagnostic and therapeutic target in breast cancer.

Mechanistic insight into the progressive retinal atrophy disease in dogs via pathway-based genome-wide association analysis

  • Sheet, Sunirmal;Krishnamoorthy, Srikanth;Park, Woncheoul;Lim, Dajeong;Park, Jong-Eun;Ko, Minjeong;Choi, Bong-Hwan
    • Journal of Animal Science and Technology
    • /
    • v.62 no.6
    • /
    • pp.765-776
    • /
    • 2020
  • The retinal degenerative disease, progressive retinal atrophy (PRA) is a major reason of vision impairment in canine population. Canine PRA signifies an inherently dissimilar category of retinal dystrophies which has solid resemblances to human retinis pigmentosa. Even though much is known about the biology of PRA, the knowledge about the intricate connection among genetic loci, genes and pathways associated to this disease in dogs are still remain unknown. Therefore, we have performed a genome wide association study (GWAS) to identify susceptibility single nucleotide polymorphisms (SNPs) of PRA. The GWAS was performed using a case-control based association analysis method on PRA dataset of 129 dogs and 135,553 markers. Further, the gene-set and pathway analysis were conducted in this study. A total of 1,114 markers associations with PRA trait at p < 0.01 were extracted and mapped to 640 unique genes, and then selected significant (p < 0.05) enriched 35 gene ontology (GO) terms and 5 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways contain these genes. In particular, apoptosis process, homophilic cell adhesion, calcium ion binding, and endoplasmic reticulum GO terms as well as pathways related to focal adhesion, cyclic guanosine monophosphate)-protein kinase G signaling, and axon guidance were more likely associated to the PRA disease in dogs. These data could provide new insight for further research on identification of potential genes and causative pathways for PRA in dogs.

Prediction of Dry Matter Intake in Lactating Holstein Dairy Cows Offered High Levels of Concentrate

  • Rim, J.S.;Lee, S.R.;Cho, Y.S.;Kim, E.J.;Kim, J.S.;Ha, Jong K.
    • Asian-Australasian Journal of Animal Sciences
    • /
    • v.21 no.5
    • /
    • pp.677-684
    • /
    • 2008
  • Accurate estimation of dry matter intake (DMI) is a prerequisite to meet animal performance targets without penalizing animal health and the environment. The objective of the current study was to evaluate some of the existing models in order to predict DMI when lactating dairy cows were offered a total mixed ration containing a high level of concentrates and locally produced agricultural by-products. Six popular models were chosen for DMI prediction (Brown et al., 1977; Rayburn and Fox, 1993; Agriculture Forestry and Fisheries Research Council Secretariat, 1999; National Research Council (NRC), 2001; Cornell Net Carbohydrate and Protein System (CNCPS), Fox et al., 2003; Fuentes-Pila et al., 2003). Databases for DMI comparison were constructed from two different sources: i) 12 commercial farm investigations and ii) a controlled dairy cow experiment. The model evaluation was performed using two different methods: i) linear regression analysis and ii) mean square error prediction analysis. In the commercial farm investigation, DMI predicted by Fuentes-Pila et al. (2003) was the most accurate when compared with the actual mean DMI, whilst the CNCPS prediction showed larger mean bias (difference between mean predicted and mean observed values). Similar results were observed in the controlled dairy cow experiment where the mean bias by Fuentes-Pila et al. (2003) was the smallest of all six chosen models. The more accurate prediction by Fuentes-Pila et al. (2003) could be attributed to the inclusion of dietary factors, particularly fiber as these factors were not considered in some models (i.e. NRC, 2001; CNCPS (Fox et al., 2003)). Linear regression analysis had little meaningful biological significance when evaluating models for prediction of DMI in this study. Further research is required to improve the accuracy of the models, and may recommend more mechanistic approaches to investigate feedstuffs (common to the Asian region), animal genotype, environmental conditions and their interaction, as the majority of the models employed are based on empirical approaches.