• Title/Summary/Keyword: p16 genes

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Diagnosis and Treatment of Myelodysplastic Syndrome in the Era of Genetic Testing (유전자 검사 시대 골수형성이상증후군의 진단과 치료)

  • Junshik Hong
    • The Korean Journal of Medicine
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    • v.99 no.1
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    • pp.11-16
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    • 2024
  • Myelodysplastic syndrome (MDS) is a heterogeneous disorder with diverse prognoses influenced by cytopenias, genetic variants, and myeloblast proportions in the bone marrow. Accurate prognosis prediction and tailored treatment plans are essential. The International Prognostic Scoring System-Molecular (IPSS-M), which additionally reflects the impact of MDS-related genetic mutations to the clinical and laboratory information, is anticipated to offer superior prognostic accuracy compared to existing systems like the Revised International Prognostic Scoring System (IPSS-R). Despite its statistical complexity, its web-based calculation and ease of discussing results with patients using intuitive data sets provide notable advantages. Progress in MDS treatment, exemplified by effective anemia correction with an erythropoiesis-maturation agent in SF3B1-mutated cases and efforts to refine poor prognoses in TP53-mutated cases, reflects the evolving landscape of genetic-based interventions in MDS. Advancements in genetic diagnostic technology, combined with enhanced knowledge of the bone marrow niche, are anticipated to lead to significant improvement in MDS treatment outcomes in the future.

Effect on Gene Expression Profile of Rat Hippocampus Caused by Administration of Memory Enhancing Herbal Extract (육미지황탕가미방이 흰쥐의 기억능력과 중추신경계 유전자 발현에 미치는 영향)

  • Choi So Eop;Bae Hyun Su;Shin Min Kyu;Hong Moo Chang
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.16 no.5
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    • pp.1025-1034
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    • 2002
  • The herbal extract (YMT_02) is a modified herbal extracts from Yukmijihwang-tang (YMJ) to promote memory-enhancing. The YMJ extracts has been widely used as an anti-aging herbal medicine for hundred years in Asian countries. The purpose of this study is to; 1) quantitatively evaluate the memory-enhancing effect of YMT_02 by behavior task, 2) identify candidate genes responsible for enhancing memory by cDNA microarray and 3) assess the anti-oxidant effect of YMT_02 on PC12 cell. Memory retention abilities are addressed by passive avoidance task with Sprague-Dawley (SD) male rat. Before the training session, the rats are subdivided into four groups and administrated with YMT_02, Ginkgo biloba, Soya lecithin and normal saline for 10 days. The retention test was performed. 24 hours after the training session. The retention time of the YMT_02 group was significantly (p<0.05) delayed (~100%), whereas Ginkgo biloba and Soya lecithin treatment delayed 20% and 10% respectively. The hippocampi of YMT_02 and control group were dissected and mANA was further purified. After synthesizing cDNA using oligo-dT primer, the cDNA were applied to Incyte rat GEMTM 2 cDNA microarray. The microarray results show that prealbumin(transthyretin), phosphotidylethanolamine N-methyltransferase, and PEP-19 are expressed abundantly in the YMT_02 treated group. Especially, PEP-19 is a neuron-specific protein, which inhibits apoptotic processes in neuronal cell. On the other hand, transcripts of RAB15, glutamate receptor subunit 2 and CDK108 are abundant in control group. Besides, neuronal genes involved in neuronal death or neurodegeneration such as neuronal-pentraxin and spectrin are abundantly expressed in control group. Additionally, the YMT_02 shows an anti oxidative effect in the PC12 cell. The list of differentially expressed genes may implicate further insight on the action and mechanism behind the memory-enhancing effect of herbal extracts YMT_02, for example, anti-apoptotic, anti-oxidative, and neuroprotective effects.

Induction of Microsomal Epoxide Hydrolase, rGSTA2, rGSTA3/5, and rGSTM1 by Disulfiram, but not by Diethyldithiocarbamate, a Reduced Form of Disulfiram

  • Kim, Sang-Geon;Kim, Hye-Jung
    • Toxicological Research
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    • v.13 no.4
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    • pp.339-347
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    • 1997
  • Disulfiram (DSF) and diethyldithiocarbamate (DDC), a reduced form of DSF, protect the liver against toxicant-induced injury through inhibition of cytochrome P450 2E1. The effect of DSF and DDC on the levels of major hepatic microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST) expression was comparatively studied, given the view that these enzymes are involved in terminal detoxification events for high energy intermediates of xenobiotics. Treatment of rats with a single dose of DSF (20-200 mg/kg, po) resulted in 2- to 15-fold increases in the mEH mRNA level at 24 hr with the ED$_{50}$ value being noted as 60 mg/kg. The mEH mRNA level was elevated ~15-fold at 24 hr after treatment at the dose of 100 mg/kg, whereas the hepatic mRNA level was rather decreased from the maximum at the dose of 200 mg/kg, indicating that DSF might cause cytotoxicity at the dose. In contrast to the effect of DSF, DDC only minimally elevated the mEH mRNA level at the doses employed. DSF moderately increased the major GST mRNA levels in the liver as a function of dose, resulting in rGSTA2, rGSTA3/5 or rGSTM1 mRNA levels being elevated 3- to 4-fold at 24 hr post-treatment, whereas the rGSTM2 mRNA level was not altered. DDC, however, failed to stimulate the mRNA levels for major GST subunits, indicating that the reduced form of DSF was ineffective in stimulating the GST the expression. The effect of other organosulfides including aldrithiol, 2, 2'-dithiobis(benzothiazole) (DTB), tetramethylthiouram disulfide (TMTD) and allyl disulfide (ADS) on the hepatic mEH and GST mRNA expression was assessed in rats in order to further confirm the increase in the gene expression by other disulfides. Treatment of rats with aldrithiol (100 mg/kg, po) resulted in a 16-fold increase in the mEH mRNA level at 24 hr post-treatment. DTB, TMTD and ADS also caused 5-, 9- and 12-fold increases in the rnRNA level, respectively, as compared to control. Thus, all of the disulfides examined were active in stimulating the mEH gene in the liver. The organosulfides significantly increased the rGSTA2, rGSTA3, rGSTA5 and rGSTM1 mRNA levels at 24 hr after administration. In particular, aldrithiol was very efficient in stimulating the rGSTA and rGSTM genes among the disulfides examined. These results provide evidence that DSF and other sulfides effectively stimulate the mEH and major GST gene expression at early times in the liver and that DDC, a reduced form of DSF, was ineffective in stimulating the expression of the genes, supporting the conclusion that reduced form(s) of organosulfur compound(s) might be less effective in inducing the mEH and GST genes through the antioxidant responsive element(s).

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Association of Single Nucleotide Polymorphisms in Interleukin-12 Receptor (IL-12Rβ1 and IL-12Rβ2) with Asthma in a Korean Population

  • Jung, Jaemee;Park, Sangjung;Kim, Sung-Soo;Hong, Mijin;Choi, Eunhye;Jin, Hyun-Seok;Hwang, Dahyun
    • Biomedical Science Letters
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    • v.26 no.4
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    • pp.344-350
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    • 2020
  • Asthma is a chronic disease and occurs in airway in the lung. The cause of the disease has not been identified, it is assumed that both genetic and environmental risk factors play an important role in the development of asthma. Interleukin (IL)-12 is a cytokine regulating T-cell and NK cell. In this study, we analyzed the genetic polymorphisms of IL-12 receptor genes (IL-12Rβ1 and IL-12Rβ2) in asthma patients and normal individuals in a Korean population. We analyzed single nucleotide polymorphisms (SNPs) in IL-12Rβ1 and IL-12Rβ2 using the genotype data of 193 asthma cases and 3,228 healthy controls from the Korea Association REsource for their correlation with asthma case. IL-12Rβ1 and IL-12Rβ2 genes showed statistically significant polymorphism association with asthma case. As a results, 16 SNPs from IL-12Rβ1 and IL-12Rβ2 genes showed statistically significant association with asthma. Among them, rs375947 SNP in IL-12Rβ1 showed the greatest statistical correlation with asthma (P-value = 0.028, Odds Ratio = 1.27, 95% Confidence Interval = 1.03~1.57). The groups with minor allele of IL-12Rβ1 and IL-12Rβ2 showed increased risk of asthma. The genotype-based mRNA expression analysis showed that the group of minor allele of IL-12Rβ1 showed decreased mRNA expression. Decreased IL-12Rβ1 expression causes decreased IL-12 signaling, and this affects developing asthma. In conclusion, the SNPs in IL-12Rβ1 and IL-12Rβ2 may contribute to development of asthma in a Korean population.

Transcriptome sequencing reveals non-coding RNAs respond to porcine reproductive and respiratory syndrome virus and Haemophilus parasuis co-infection in Kele piglets

  • Jing Zhang;Chunping Zhao;Min Yao;Jing Qi;Ya Tan;Kaizhi Shi;Jing Wang;Sixuan Zhou;Zhixin Li
    • Journal of Animal Science and Technology
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    • v.66 no.4
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    • pp.663-681
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    • 2024
  • Co-infection with porcine reproductive and respiratory syndrome virus (PRRSV) and Haemophilus parasuis (HPS) has severely restricted the healthy development of pig breeding. Exploring disease resistance of non-coding RNAs in pigs co-infected with PRRSV and HPS is therefore critical to complement and elucidate the molecular mechanisms of disease resistance in Kele piglets and to innovate the use of local pig germplasm resources in China. RNA-seq of lungs from Kele piglets with single-infection of PRRSV or HPS and co-infection of both pathogens was performed. Two hundred and twenty-five differentially expressed long non-coding RNAs (DElncRNAs) and 30 DEmicroRNAs (DEmiRNAs) were identified and characterized in the PRRSV and HPS co-infection (PRRSV-HPS) group. Compared with the single-infection groups, 146 unique DElncRNAs, 17 unique DEmiRNAs, and 206 target differentially expressed genes (DEGs) were identified in the PRRSV-HPS group. The expression patterns of 20 DEmiRNAs and DElncRNAs confirmed by real-time quantitative polymerase chain reaction (RT-qPCR) were consistent with those determined by high-throughput sequencing. In the PRRSV-HPS group, the target DEGs were enriched in eight immune Gene Ontology terms relating to two unique DEmiRNAs and 16 DElncRNAs, and the unique target DEGs participated the host immune response to pathogens infection by affecting 15 immune-related Kyoto Encyclopedia of Genes and Genomes enrichment pathways. Notably, competitive endogenous RNA (ceRNA) networks of different groups were constructed, and the ssc-miR-671-5p miRNA was validated as a potential regulatory factor to regulate DTX4 and AEBP1 genes to achieve innate antiviral effects and inhibit pulmonary fibrosis by dual-luciferase reporter assays. These results provided insight into further study on the molecular mechanisms of resistance to PRRSV and HPS co-infection in Kele piglets.

Diversity of Uncultured Microorganisms Associated with the Anaerobic Pentachlorophenol Degradation Estimated by Comparative RELP Analysis of PCR-Amplified 16S rDNA Clones (16S rDNA 클론들의 RFLP 비교분석에서 얻어진 Pentachlorophenol의 혐기성 분해에 따른 미생물군집의 변화)

  • 성창수;권오섭;박영식
    • Korean Journal of Microbiology
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    • v.33 no.2
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    • pp.149-156
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    • 1997
  • We have employed comparative RFL,P(Restriction Fragment Ixngth Pol~iniorphism) analysis and molecular phylogenetic techniques to investigate the diversity of uncultured microorganisms associated with the anaerobic PCP degradation in PCP-adapted enrichment cultures inoculated by samples from anaerobic cewage sludgc(Jangrim, Pusan) and leachate of landfill site(Kimhae). 16s rDNA cloncs were obtairted by PCR amplification of mixed population DNAs extracted directly from the nonactive and active stage ol each PCP-adapted culture. After three rounds of comparative RFLP analyses. two RFLP types. designated as Ala and Hld, were found prevalent and common in both active stage samples. Thc analysis of phylogenctic diversity bawd on the 5'-terminal 180 nt of sequences from whole clones of the Ala and Bld RFLP types showed close similarity among themselves. In case of Bld clones, 7XQ of them shared identical sequences. Thcse resuliq suggest that the clones of both RFLP types wcre originated from highly affiliated microorganisms which are e~iriched as a result of metabolic activity to PCP. The full-length 16s rRNA sequence of each representative clone from both RFLP types was determined. and an Ala clone w i n found to he related to Clo.strrdiurn ulfutzac~(Genk~ank No. Z69203) and a Bld clone to Thermobacteroides proteolyticus(Genbank No. X09335), with sequence similarities of 89%' and 97%. respectively.

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Secondary Metabolites Production and Plant Growth Promotion by Pseudomonas chlororaphis and P. aurantiaca Strains Isolated from Cactus, Cotton, and Para Grass

  • Shahid, Izzah;Rizwan, Muhammad;Baig, Deeba Noreen;Saleem, Rahman Shahzaib;Malik, Kauser A.;Mehnaz, Samina
    • Journal of Microbiology and Biotechnology
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    • v.27 no.3
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    • pp.480-491
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    • 2017
  • Fluorescent pseudomonads have been isolated from halophytes, mesophytes, and xerophytes of Pakistan. Among these, eight isolates, GS-1, GS-3, GS-4, GS-6, GS-7, FS-2 (cactus), ARS-38 (cotton), and RP-4 (para grass), showed antifungal activity and were selected for detailed study. Based on biochemical tests and 16S rRNA gene sequences, these were identified as strains of P. chlororaphis subsp. chlororaphis and aurantiaca. Secondary metabolites of these strains were analyzed by LC-MS. Phenazine-1-carboxylic acid (PCA), 2-hydroxy-phenazine, Cyclic Lipopeptide (white line-inducing principle (WLIP)), and lahorenoic acid A were detected in variable amounts in these strains. P. aurantiaca PB-St2 was used as a reference as it is known for the production of these compounds. The phzO and PCA genes were amplified to assure that production of these compounds is not an artifact. Indole acetic acid production was confirmed and quantified by HPLC. HCN and siderophore production by all strains was observed by plate assays. These strains did not solubilize phosphate, but five strains were positive for zinc solubilization. Wheat seedlings were inoculated with these strains to observe their effect on plant growth. P. aurantiaca strains PB-St2 and GS-6 and P. chlororaphis RP-4 significantly increased both root and shoot dry weights, as compared with uninoculated plants. However, P. aurantiaca strains FS-2 and ARS-38 significantly increased root and shoot dry weights, respectively. All strains except PB-St2 and ARS-38 significantly increased the root length. This is the first report of the isolation of P. aurantiaca from cotton and cactus, P. chlororaphis from para grass, WLIP and lahorenoic acid A production by P. chlororaphis, and zinc solubilization by P. chlororaphis and P. aurantiaca.

Analysis of Poly(3-Hydroxybutyrate) Granule-Associated Proteome in Recombinant Escherichia coli

  • Han Mee-Jung;Park Si-Jae;Lee Jeong-Wook;Min Byoung-Hoon;Lee Sang-Yup;Kim Soo-Jin;Yoo Jong-Shin
    • Journal of Microbiology and Biotechnology
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    • v.16 no.6
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    • pp.901-910
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    • 2006
  • Poly(3-hydroxybutyrate) [P(3HB)] is a microbial polyester intracellularly accumulated as distinct granules in numerous microorganisms as an energy and carbon storage material. Recombinant Escherichia coli harboring the heterologous P(3HB) biosynthesis genes accumulates large amounts of P(3HB) granules, yet the granule-associated proteins have not been identified. Therefore, this study reports on an analysis of the P(3HB) granule-associated proteome in recombinant E. coli. Fiye proteins out of 7 spots identified were found to be involved in functions of translation, heat-stress responses, and P(3HB) biosynthesis. Two of the major granule-associated proteins, IbpA/B, which are already known to bind to recombinant proteins forming inclusion bodies in E. coli, were further analyzed. Immunoblotting and immunoelectron microscopic studies with IbpA/B antibodies clearly demonstrated the binding and localization of IbpA/B to P(3HB) granules. IbpA/B seemed to play an important role in recombinant E. coli producing P(3HB) by stabilizing the interface between the hydrophobic P(3HB) granules and the hydrophilic cytoplasm. Thus, IbpA/B were found to act like phasins in recombinant E. coli, as they are the major proteins bound to the P(3HB) granules, affect the morphology of the granules, and reduce the amount of cytosolic proteins bound to the P(3HB) granules.

Biosynthesis of Lactate-containing Polyhydroxyalkanoates in Recombinant Escherichia coli from Sucrose (재조합 대장균에서 수크로즈로부터의 젖산을 모노머로 함유한 폴리하이드록시알칸산 생산 연구)

  • Oh, Young Hoon;Kang, Kyoung-Hee;Shin, Jihoon;Song, Bong Keun;Lee, Seung Hwan;Lee, Sang Yup;Park, Si Jae
    • KSBB Journal
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    • v.29 no.6
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    • pp.443-447
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    • 2014
  • Biosynthesis of lactate-containing polyhydroxyalkanoates (PHAs) was examined in recombinant Escherichia coli W strain from sucrose. The Pseudomonas sp. MBEL 6-19 phaC1437 gene and the Clostridium propionicum pct540 gene, which encode engineered Pseudomonas sp. MBEL 6-19 PHA synthase 1 ($PhaC1_{Ps6-19}$) and engineered C. propionicum propionyl-CoA transferase ($Pct_{Cp}$), respectively, were expressed in E. coli W to construct key metabolic pathway to produce poly(3-hydroxybutyrate-co-lactate) [P(3HB-co-LA)]. The recombinant E. coli W expressing the phaC1437 gene and the pct540 gene could synthesize P(3HB-co-13mol%LA) up to the polymer content of 31.3 wt% when it was cultured in chemically defined MR medium containing 20 g/L of sucrose and 2 g/L of sodium 3-hydroxybutyrate. When Ralstonia eutropha phaAB genes were additionally expressed to provide 3-hydroxybutyrate-CoA (3HB-CoA) from sucrose, P(3HB-co-16mol%LA) could be synthesized from sucrose as a sole carbon source without supplement of sodium 3-hydroxybutyrate in culture medium, but the PHA content was decreased to 12.2 wt%. The molecular weight of P(3HB-co-16 mol%LA) synthesized in E. coli W using sucrose as carbon source were $1.53{\times}10^4$ ($M_n$) and $2.78{\times}10^4$ ($M_w$), respectively, which are not different from those that have previously been reported by other recombinant E. coli strains. Engineered E. coli strains developed in this study should be useful for the production of lactate-containing PHAs from sucrose, one of the most abundant and least expensive carbon sources.

Variance Component Quantitative Trait Locus Analysis for Body Weight Traits in Purebred Korean Native Chicken

  • Cahyadi, Muhammad;Park, Hee-Bok;Seo, Dong-Won;Jin, Shil;Choi, Nuri;Heo, Kang-Nyeong;Kang, Bo-Seok;Jo, Cheorun;Lee, Jun-Heon
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.1
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    • pp.43-50
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    • 2016
  • Quantitative trait locus (QTL) is a particular region of the genome containing one or more genes associated with economically important quantitative traits. This study was conducted to identify QTL regions for body weight and growth traits in purebred Korean native chicken (KNC). F1 samples (n = 595) were genotyped using 127 microsatellite markers and 8 single nucleotide polymorphisms that covered 2,616.1 centi Morgan (cM) of map length for 26 autosomal linkage groups. Body weight traits were measured every 2 weeks from hatch to 20 weeks of age. Weight of half carcass was also collected together with growth rate. A multipoint variance component linkage approach was used to identify QTLs for the body weight traits. Two significant QTLs for growth were identified on chicken chromosome 3 (GGA3) for growth 16 to18 weeks (logarithm of the odds [LOD] = 3.24, Nominal p value = 0.0001) and GGA4 for growth 6 to 8 weeks (LOD = 2.88, Nominal p value = 0.0003). Additionally, one significant QTL and three suggestive QTLs were detected for body weight traits in KNC; significant QTL for body weight at 4 weeks (LOD = 2.52, nominal p value = 0.0007) and suggestive QTL for 8 weeks (LOD = 1.96, Nominal p value = 0.0027) were detected on GGA4; QTLs were also detected for two different body weight traits: body weight at 16 weeks on GGA3 and body weight at 18 weeks on GGA19. Additionally, two suggestive QTLs for carcass weight were detected at 0 and 70 cM on GGA19. In conclusion, the current study identified several significant and suggestive QTLs that affect growth related traits in a unique resource pedigree in purebred KNC. This information will contribute to improving the body weight traits in native chicken breeds, especially for the Asian native chicken breeds.