• Title/Summary/Keyword: p16 genes

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Signal Transduction Events Elicited by Natural Products: Role of MAPK and Caspase Pathways in Homeostatic Response and Induction of Apoptosis

  • Kong, Ah-Ng Tony;Yu, Rong;Chen, Chi;Mandlekar, Sandhya;Primiano, Thomas
    • Archives of Pharmacal Research
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    • v.23 no.1
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    • pp.1-16
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    • 2000
  • Many natural products elicit diverse pharmacological effects. Using two classes of potential chemopreventive compounds, the phenolic compounds and the isothiocyanates, we review the potential utility of two signaling events, the mitogen-activated protein kinases (MAPKs) and the ICE/Ced-3 proteases (caspases) stimulated by these agents in mammalian cell lines. Studies with phenolic antioxidants (BHA, tBHQ), and natural products (flavonoids; EGCG, ECG, and isothiocyanates; PEITC, sulforaphane), provided important insights into the signaling pathways induced by these compounds. At low concentrations, these chemicals may activate the MAPK (ERK2, JNK1, p38) leading to gene expression of survival genes (c-Fos, c-Jun) and defensive genes (Phase II detoxifying enzymes; GST, QR) resulting in survival and protective mechanisms (homeostasis response). Increasing the concentrations of these compounds will additionally activate the caspase pathway, leading to apoptosis (potential cytotoxicity). Further increment to suprapharmacological concentrations will lead to nonspecific necrotic cell death. The wider and narrow concentration ranges between the activation of MAPK/gene induction and caspases/cell death exhibited by phenolic compounds and isothiocyanates, respectively, in mammalian cells, may reflect their respective therapeutic windows in vivo. Consequently, the studies of signaling pathways elicited by natural products will advance our understanding of their efficacy and safety, of which many man become important therapeuitc drugs of the future.

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Analysis of copy number variation in 8,842 Korean individuals reveals 39 genes associated with hepatic biomarkers AST and ALT

  • Kim, Hyo-Young;Cho, Seo-Ae;Yu, Jeong-Mi;Sung, Sam-Sun;Kim, Hee-Bal
    • BMB Reports
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    • v.43 no.8
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    • pp.547-553
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    • 2010
  • Biochemical tests such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are useful for diagnosing patients with liver disease. In this study, we tested the association between copy number variation and the hepatic biomarkers AST and ALT based on 8,842 samples from population-based cohorts in Korea. We used Affymetrix Genome-Wide Human 5.0 arrays and identified 10,534 CNVs using HelixTree software. Of the CNVs tested using univariate linear regression, 100 CNVs were significant for AST and 16 were significant for ALT (P < 0.05). We identified 39 genes located within the CNV regions. DKK1 and HS3ST3B1 were shown to play roles in heparan sulfate biosynthesis and the Wnt signaling pathway, respectively. NAF1 and NPY1R were associated with glycoprotein processes and neuropeptide Y receptor activity based on GO categories. PTER, SOX14 and TM7SF4 were expressed in liver. DPYS and CTSC were found to be associated with dihydropyrimidinuria and Papillon-Lefevre syndrome phenotypes using OMIM. NPY5R was found to be associated with dyslipidemia using the Genetic Association Database.

Sinapic acid induces the expression of thermogenic signature genes and lipolysis through activation of PKA/CREB signaling in brown adipocytes

  • Hossain, Monir;Imran, Khan Mohammad;Rahman, Md. Shamim;Yoon, Dahyeon;Marimuthu, Vignesh;Kim, Yong-Sik
    • BMB Reports
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    • v.53 no.3
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    • pp.142-147
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    • 2020
  • Lipid accumulation in white adipose tissue is the key contributor to the obesity and orchestrates numerous metabolic health problems such as type 2 diabetes, hypertension, atherosclerosis, and cancer. Nonetheless, the prevention and treatment of obesity are still inadequate. Recently, scientists found that brown adipose tissue (BAT) in adult humans has functions that are diametrically opposite to those of white adipose tissue and that BAT holds promise for a new strategy to counteract obesity. In this study, we evaluated the potential of sinapic acid (SA) to promote the thermogenic program and lipolysis in BAT. SA treatment of brown adipocytes induced the expression of brown-adipocyte activation-related genes such as Ucp1, Pgc-1α, and Prdm16. Furthermore, structural analysis and western blot revealed that SA upregulates protein kinase A (PKA) phosphorylation with competitive inhibition by a pan-PKA inhibitor, H89. SA binds to the adenosine triphosphate (ATP) site on the PKA catalytic subunit where H89 binds specifically. PKA-cat-α1 gene-silencing experiments confirmed that SA activates the thermogenic program via a mechanism involving PKA and cyclic AMP response element-binding protein (CREB) signaling. Moreover, SA treatment promoted lipolysis via a PKA/p38-mediated pathway. Our findings may allow us to open a new avenue of strategies against obesity and need further investigation.

Multifactor Dimensionality Reduction (MDR) Analysis to Detect Single Nucleotide Polymorphisms Associated with a Carcass Trait in a Hanwoo Population

  • Lee, Jea-Young;Kwon, Jae-Chul;Kim, Jong-Joo
    • Asian-Australasian Journal of Animal Sciences
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    • v.21 no.6
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    • pp.784-788
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    • 2008
  • Studies to detect genes responsible for economic traits in farm animals have been performed using parametric linear models. A non-parametric, model-free approach using the 'expanded multifactor-dimensionality reduction (MDR) method' considering high dimensionalities of interaction effects between multiple single nucleotide polymorphisms (SNPs), was applied to identify interaction effects of SNPs responsible for carcass traits in a Hanwoo beef cattle population. Data were obtained from the Hanwoo Improvement Center, National Agricultural Cooperation Federation, Korea, and comprised 299 steers from 16 paternal half-sib proven sires that were delivered in Namwon or Daegwanryong livestock testing stations between spring of 2002 and fall of 2003. For each steer at approximately 722 days of age, the Longssimus dorsi muscle area (LMA) was measured after slaughter. Three functional SNPs (19_1, 18_4, 28_2) near the microsatellite marker ILSTS035 on BTA6, around which the QTL for meat quality were previously detected, were assessed. Application of the expanded MDR method revealed the best model with an interaction effect between the SNPs 19_1 and 28_2, while only one main effect of SNP19_1 was statistically significant for LMA (p<0.01) under a general linear mixed model. Our results suggest that the expanded MDR method better identifies interaction effects between multiple genes that are related to polygenic traits, and that the method is an alternative to the current model choices to find associations of multiple functional SNPs and/or their interaction effects with economic traits in livestock populations.

3D-culture models as drug-testing platforms in canine lymphoma and their cross talk with lymph node-derived stromal cells

  • An, Ju-Hyun;Song, Woo-Jin;Li, Qiang;Bhang, Dong-Ha;Youn, Hwa-Young
    • Journal of Veterinary Science
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    • v.22 no.3
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    • pp.25.1-25.16
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    • 2021
  • Background: Malignant lymphoma is the most common hematopoietic malignancy in dogs, and relapse is frequently seen despite aggressive initial treatment. In order for the treatment of these recurrent lymphomas in dogs to be effective, it is important to choose a personalized and sensitive anticancer agent. To provide a reliable tool for drug development and for personalized cancer therapy, it is critical to maintain key characteristics of the original tumor. Objectives: In this study, we established a model of hybrid tumor/stromal spheroids and investigated the association between canine lymphoma cell line (GL-1) and canine lymph node (LN)-derived stromal cells (SCs). Methods: A hybrid spheroid model consisting of GL-1 cells and LN-derived SC was created using ultra low attachment plate. The relationship between SCs and tumor cells (TCs) was investigated using a coculture system. Results: TCs cocultured with SCs were found to have significantly upregulated multidrug resistance genes, such as P-qp, MRP1, and BCRP, compared with TC monocultures. Additionally, it was revealed that coculture with SCs reduced doxorubicin-induced apoptosis and G2/M cell cycle arrest of GL-1 cells. Conclusions: SCs upregulated multidrug resistance genes in TCs and influenced apoptosis and the cell cycle of TCs in the presence of anticancer drugs. This study revealed that understanding the interaction between the tumor microenvironment and TCs is essential in designing experimental approaches to personalized medicine and to predict the effect of drugs.

Composition and Diversity of Salivary Microbiome Affected by Sample Collection Method

  • Lee, Yeon-Hee;Hong, Ji-Youn;Lee, Gi-Ja
    • Journal of Oral Medicine and Pain
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    • v.47 no.1
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    • pp.10-26
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    • 2022
  • Purpose: The purpose of this study was to investigate whether various saliva collection methods affect the observed salivary microbiome and whether microbiomes of stimulated and unstimulated saliva and plaque differ in richness and diversity. Methods: Seven sampling methods for unstimulated saliva, stimulated saliva, and plaque samples were applied to six orally and systemically healthy participants. Bacterial 16S ribosomal RNA genes of 10 major oral bacterial species, namely, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum, Prevotella intermedia, Prevotella nigrescens, Streptococcus mitis, Streptococcus sobrinus, and Lactobacillus casei, were analyzed by real-time polymerase chain reaction. We comprehensively examined the dependence of the amount of bacterial ribosomal DNA (rDNA), bacterial-community composition, and relative abundance of each species on sample collection methods. Results: There were significant differences in the bacterial rDNA copy number depending on the collection method in three species: F. nucleatum, P. nigrescens, and S. mitis. The species with the highest richness was S. mitis, with the range from 89.31% to 100.00%, followed by F. nucleatum, P. nigrescens, T. denticola, T. forsythia, and P. intermedia, and the sum of the proportions of the remaining five species was less than 1%. The species with the lowest observed richness was P. gingivalis (<0.1%). The Shannon diversity index was the highest in unstimulated saliva collected with a funnel (4.449). The Shannon diversity index was higher in plaque samples (3.623) than in unstimulated (3.171) and stimulated (3.129) saliva and in mouthwash saliva samples (2.061). Conclusions: The oral microbial profile of saliva samples can be affected by sample collection methods, and saliva differs from plaque in the microbiome. An easy and rapid technique for saliva collection is desirable; however, observed microbial-community composition may more accurately reflect the actual microbiome when unstimulated saliva is assayed.

Ramipedicella gen. nov. (Ralfsiales, Phaeophyceae): a new crustose brown algal genus including two species, Ramipedicella miniloba sp. nov. and Ramipedicella longicellularis comb. nov.

  • Antony Otinga Oteng'o;Boo Yeon Won;Tae Oh Cho
    • ALGAE
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    • v.39 no.2
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    • pp.97-108
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    • 2024
  • The Ralfsiaceae family, part of the Ralfsiales order and consisting of crustose brown algae, includes five genera: Analipus, Endoplura, Fissipedicella, Heteroralfsia, and Ralfsia. In this study, a novel crustose genus named Ramipedicella gen. nov. is introduced within the Ralfsiaceae based on molecular and morphological analyses. Phylogenetic analyses using both concatenated dataset (rbcL + COI-5P genes) and rbcL indicate that the crustose brown algae that we collected from Korea and Russia form a unique grouping within the Ralfsiaceae. This grouping is strongly supported by both bootstrap analysis and Bayesian posterior probabilities. The genetic differences in the rbcL and COI-5P sequences between Ramipedicella and other genera within Ralfsiaceae range from 6.7 to 9.3% for rbcL and from 15.5 to 20.8% for COI-5P. Ramipedicella is characterized by crustose thalli having new crusts growing on top of old ones with a hypothallial basal layer and erect perithallial filaments, long cells with width-to-length ratio of 1 : 1-16, single chloroplast per cell, plurangia with one to several sterile cells, one to several unangia produced from unicellular stalks or from the lateral-basal region to the paraphyses, and unangia arising sequencially in irregularly branched specialized filaments. Ramipedicella, the recently identified genus, comprises two distinct species. Ramipedicella miniloba, the type species, is distinguished by crusts with small lobes, numerous hair tufts, plurangia terminated by 1-4 sterile cells, and large oblong unangia. Ramipedicella longicellularis is identified by generally smooth crusts, absence of phaeophycean hairs, plurangia terminated by 1-2 apical sterile cells, and smaller mostly oblanceolate unangia.

Pseudomonas tolaasii bacteriophage-specific polyclonal antibody formation and its cross reactivity to various phages (Pseudomonas tolaasii 박테리오파지에 특이적인 다클론항체 형성 및 이를 이용한 파지 교차 반응성)

  • Yun, Yeong-Bae;Park, Soo-Jin;Kim, Young-Kee
    • Journal of Applied Biological Chemistry
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    • v.62 no.3
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    • pp.287-292
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    • 2019
  • Pseudomonas tolaasii causes brown blotch disease on the oyster mushroom (Pleurotus ostreatus). Various pathogenic strains of P. tolaasii were isolated and divided into three subtypes, $P1{\alpha}$, $P1{\beta}$, and $P1{\gamma}$. For phage therapy, bacteriophages against to these subtype strains were applied to mushroom cultivation and very successful to prevent from the disease. In this study, bacteriophages were isolated against the representative strains of subtype pathogens and their polyclonal antibodies were synthesized to investigate structural relationship among capsid proteins of phages. Phage preparations over $10^{10}pfu/mL$ were injected to rabbit thigh muscle and polyclonal antibodies were obtained after three times of boost injection. Titers of the antibodies obtained were over $2{\times}10^7Ab/mL$ for the phage ${\phi}6264$, $1{\times}10^6Ab/mL$ for the phage ${\phi}HK2$, and $1{\times}10^7Ab/mL$ for the phage ${\phi}HK19$ and phage ${\phi}HK23$. High specific activities were observed between antibodies and the corresponding bacteriophages. Some cross-reactivities between the antibodies and non-corresponding bacteriophages were also measured. Antibody $Ab{\phi}6264$ inactivated all phages of $P1{\alpha}$ subtype and only phage ${\phi}HK16$ among $P1{\beta}$ subtype phages. Antibody $Ab{\phi}HK23$ of $P1{\gamma}$ subtype neutralized all phages of $P1{\beta}$ subtype as well as the phage ${\phi}HK23$, showing the widest phage-inactivation range. When the structural-similarity studies of phages were investigated by using phage antibodies, closeness obtained by phylogenetic analysis of 16S rRNA genes of pathogenic strains were quite different from that of polyclonal antibody-specific structural similarity of phage capsid proteins. In conclusion, there is weak correlation between the host strain specificity of bacteriophage and its capsid structural similarity measured by phage antibodies.

Expression Analysis of Anthocyanin Biosynthetic Genes of Tassel and Silks in Gwangpyeongok and Dacheongok (광평옥과 다청옥의 수이삭과 수염에서 안토시아닌 생합성 유전자 발현 분석)

  • Go, Young Sam;Bae, Hwan Hee;Choi, Yu Chan;Son, Jae Han;Ha, Jun Young;Shin, Seong Hyu;Jung, Tae Wook
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.66 no.3
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    • pp.240-247
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    • 2021
  • Anthocyanins are known to be involved in various functions such as antioxidant and antibacterial activities in plants. Although studies on anthocyanins in corn have been conducted recently, basic research related to anthocyanin biosynthesis is insufficient. In this study, we examined the molecular biological and physicochemical properties related to anthocyanin biosynthesis in the tassel and silks of Gwangpyeongok and Dacheongok cultivars. Anthocyanins were not synthesized in either the tassel or silks in Gwangpyeongok, whereas were synthesized in both in Dacheongok. The total anthocyanin content was approximately 30 times higher in the tassel and silks of Dacheongok than in those of Gwangpyeongok. In addition, C-3-G was measured only in the tassel of Dacheongok, and C-3-G, Pg-3-G, and M-3-G were 45.2 times, 27.3 times, and 37.6 times higher, respectively, in the silks of Dacheongok than of Gwangpyeongok. Expression of F3'H, DFR, and GST genes decreased in the tassel, and that of F3'H and DFR genes decreased in the silks of Gwangpyeongok. It was further confirmed that transcription factor P1 and R1 regulate the expression of anthocyanin biosynthetic genes in the tassel and silks, respectively, in Gwangpyeongok. Linoleic acid (C18:2) decreased by 6.6% and 10.9%, and linolenic acid (C18:3) increased by 8.5% and 8.5%, in the tassel and silks, respectively, of Gwangpyeongok compared to those of Dacheongok. Palmitic acid (C16:0) increased by 4.1% and oleic acid (C18:1) decreased by 2.1% in the silks of Gwangpyeongok compared to that in Dacheongok. In addition, the total fatty acid content in the tassel and silks increased by 10.3% and 30.4%, respectively, in Gwangpyeongok compared to that in Dacheongok. However, no significant results were observed in the analysis of phytosterol components. These results may be utilized as useful resources for the development of functional corn containing a large amount of anthocyanins.

Comparison of Fecal Microbiota of Mongolian and Thoroughbred Horses by High-throughput Sequencing of the V4 Region of the 16S rRNA Gene

  • Zhao, Yiping;Li, Bei;Bai, Dongyi;Huang, Jinlong;Shiraigo, Wunierfu;Yang, Lihua;Zhao, Qinan;Ren, Xiujuan;Wu, Jing;Bao, Wuyundalai;Dugarjaviin, Manglai
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.9
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    • pp.1345-1352
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    • 2016
  • The hindgut of horses is an anaerobic fermentative chamber for a complex and dynamic microbial population, which plays a critical role in health and energy requirements. Research on the gut microbiota of Mongolian horses has not been reported until now as far as we know. Mongolian horse is a major local breed in China. We performed high-throughput sequencing of the 16S rRNA genes V4 hypervariable regions from gut fecal material to characterize the gut microbiota of Mongolian horses and compare them to the microbiota in Thoroughbred horses. Fourteen Mongolian and 19 Thoroughbred horses were used in the study. A total of 593,678 sequence reads were obtained from 33 samples analyzed, which were found to belong to 16 phyla and 75 genera. The bacterial community compositions were similar for the two breeds. Firmicutes (56% in Mongolian horses and 53% in Thoroughbred horses) and Bacteroidetes (33% and 32% respectively) were the most abundant and predominant phyla followed by Spirochaete, Verrucomicrobia, Proteobacteria, and Fibrobacteres. Of these 16 phyla, five (Synergistetes, Planctomycetes, Proteobacteria, TM7, and Chloroflexi) were significantly different (p<0.05) between the two breeds. At the genus level, Treponema was the most abundant genus (43% in Mongolian horses vs 29% in Thoroughbred horses), followed by Ruminococcus, Roseburia, Pseudobutyrivibrio, and Anaeroplasma, which were detected in higher distribution proportion in Mongolian horses than in Thoroughbred horses. In contrast, Oscillibacter, Fibrobacter, Methanocorpusculum, and Succinivibrio levels were lower in Mongolian horses. Among 75 genera, 30 genera were significantly different (p<0.05) between the two breeds. We found that the environment was one of very important factors that influenced horse gut microbiota. These findings provide novel information about the gut microbiota of Mongolian horses and a foundation for future investigations of gut bacterial factors that may influence the development and progression of gastrointestinal disease in horses.