• 제목/요약/키워드: Bioinformatics study

검색결과 757건 처리시간 0.026초

Increased Lymphocyte Infiltration in Rheumatoid Arthritis Is Correlated with an Increase in LTi-like Cells in Synovial Fluid

  • Koo, Jihye;Kim, Soochan;Jung, Woong Jae;Lee, Ye Eun;Song, Gwan Gyu;Kim, Kyung-Su;Kim, Mi-Yeon
    • IMMUNE NETWORK
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    • 제13권6호
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    • pp.240-248
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    • 2013
  • In this study, we compared the immune cell populations in rheumatoid arthritis (RA) synovial fluid, which shows lymphoid tissue-like structure, with those in tonsils, which are normal secondary lymphoid tissues. Firstly, we found that $CD4^-CD11b^+$ macrophages were the major population in RA synovial fluid and that B cells were the major population in tonsils. In addition, synovial fluid from patients with osteoarthritis, which is a degenerative joint disease, contained $CD4^+CD11b^+$monocytes as the major immune cell population. Secondly, we categorized three groups based on the proportion of macrophages found in RA synovial fluid: (1) the macrophage-high group, which contained more than 80% macrophages; (2) the macrophage-intermediate group, which contained between 40% and 80% macrophages; and (3) the macrophage-low group, which contained less than 40% macrophages. In the macrophage-low group, more lymphoid tissue inducer (LTi)-like cells were detected, and the expression of OX40L and TRANCE in these cells was higher than that in the other groups. In addition, in this group, the suppressive function of regulatory T cells was downregulated. Finally, CXCL13 expression was higher in RA synovial fluid than in tonsils, but CCL21 expression was comparable in synovial fluid from all groups and in tonsils. These data demonstrate that increased lymphocyte infiltration in RA synovial fluid is correlated with an increase in LTi-like cells and the elevation of the chemokine expression.

Novel DOT1L ReceptorNatural Inhibitors Involved in Mixed Lineage Leukemia: a Virtual Screening, Molecular Docking and Dynamics Simulation Study

  • Raj, Utkarsh;Kumar, Himansu;Gupta, Saurabh;Varadwaj, Pritish Kumar
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권9호
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    • pp.3817-3825
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    • 2015
  • Background: The human protein methyl-transferase DOT1L catalyzes the methylation of histone H3 on lysine 79 (H3K79) at homeobox genes and is also involved in a number of significant processes ranging from gene expression to DNA-damage response and cell cycle progression. Inhibition of DOT1L activity by shRNA or small-molecule inhibitors has been established to prevent proliferation of various MLL-rearranged leukemia cells in vitro, establishing DOT1L an attractive therapeutic target for mixed lineage leukemia (MLL). Most of the drugs currently in use for the MLL treatment are reported to have low efficacy, hence this study focused on various natural compounds which exhibit minimal toxic effects and high efficacy for the target receptor. Materials and Methods: Structures of human protein methyl-transferase DOT1L and natural compound databases were downloaded from various sources. Virtual screening, molecular docking, dynamics simulation and drug likeness studies were performed for those natural compounds to evaluate and analyze their anti-cancer activity. Results: The top five screened compounds possessing good binding affinity were identified as potential high affinity inhibitors against DOT1L's active site. The top ranking molecule amongst the screened ligands had a Glide g-score of -10.940 kcal/mol and Glide e-model score of -86.011 with 5 hydrogen bonds and 12 hydrophobic contacts. This ligand's behaviour also showed consistency during the simulation of protein-ligand complex for 20000 ps, which is indicative of its stability in the receptor pocket. Conclusions: The ligand obtained out of this screening study can be considered as a potential inhibitor for DOT1L and further can be treated as a lead for the drug designing pipeline.

Potential Risk Factors for Breast Cancer in Pakistani Women

  • Bano, Raisa;Ismail, Muhammad;Nadeem, Aamer;Khan, Mohammad Haroon;Rashid, Hamid
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권9호
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    • pp.4307-4312
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    • 2016
  • Background: Breast cancer is the most common female malignancy worldwide and its incidence is on the rise in Pakistan. The aim of this case-control study was to quantify the association of various risk factors with breast cancer risk among Pakistani women. Materials and Methods: A total of 2,246 women were studied, including 1,238 women with histologically confirmed breast cancer patients and age matched control subjects (N=1008) without breast cancer and other chronic diseases. Subjects were interviewed using a specifically designed questionnaire. Unconditional logistic regression was applied. Subsequent disease-specific mortality was also measured. Results: In this study, majority of the breast cancer patients (69.59%) were in age ranges of 40s and 50s. BMI greater than 25kg/m2 (OR=1.57; 95%CI, 1.26-1.90 and OR=1.60; 95%CI, 1.26-2.03), marital status of unmarried (OR=2.03; 95%CI, 1.69-2.44), lack of breast feeding, smoking (current or ever), lack of physical activity and post-menopausal status were found to have significant positive associations with breast cancer. It was also observed that increased parity reduced the disease risk. A larger number of cases (58.1%) had their right breast affected while 22.8% had other complications as well. Conclusions: This exploratory analysis indicated a number of risk factors to be associated with increased risk of breast cancer. It was also observed that mean age at diagnosis is a decade earlier than in western countries. It is hoped that our findings will facilitate establishment of adequate evidence-based awareness and preventive measures for Pakistani women.

Bioinformatics Study and Experimental Evaluation of miR-182, and miR-34 Expression Profiles in Tuberculosis and Lung Cancer

  • Leila Alimardanian;Bahram Mohammad Soltani;Shiva Irani;Mojgan Sheikhpour
    • Tuberculosis and Respiratory Diseases
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    • 제87권3호
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    • pp.398-408
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    • 2024
  • Background: Lung cancer is one of the most dangerous cancers and tuberculosis is one of the deadliest infectious diseases in the world. Many studies have confirmed the connection between lung cancer and tuberculosis, and also the microRNAs (miRNAs) that play a major role in the development of these two diseases. This study aims to use different databases to find effective miRNAs and their role in different genes in lung and tuberculosis diseases. It also aims to determine the role of miR-34a and miR-182 in lung cancer and tuberculosis. Methods: Using the Gene Expression Omnibus (GEO) database, the influential miRNA databases were studied in the two diseases. Finally, considering bioinformatics results and literature studies, two miR-34a and miR-182 were selected. The role of these miRNAs and their target genes was carefully evaluated using bioinformatics. The expression of miRNAs in the plasma of patients with lung cancer and tuberculosis and healthy individuals was investigated. Results: According to the GEO database, miR-34a and miR-182 are miRNAs that affect tuberculosis and lung cancer. By checking the miRBase, miRcode, DIANA, miRDB, galaxy, Kyoto Encyclopedia of Genes and Genomes databases, the role of these miRNAs on genes and different molecular pathways and their effect on these miRNAs were mentioned. The results of the present study showed that the expression of miR-34a and miR-182 was lower than that of healthy people. The p-value for miR-182 was <0.0001 and for miR-34a was 0.3380. Conclusion: Reducing the expression pattern of these miRNAs indicates their role in lung cancer and tuberculosis occurrence. Therefore, these miRNAs can be used as a biomarker for prognosis, diagnosis, and treatment methods.

Effects of Dietary Fat Types on Growth Performance, Pork Quality, and Gene Expression in Growing-finishing Pigs

  • Park, J.C.;Kim, S.C.;Lee, S.D.;Jang, H.C.;Kim, N.K.;Lee, S.H.;Jung, H.J.;Kim, I.C.;Seong, H.H.;Choi, Bong-Hwan
    • Asian-Australasian Journal of Animal Sciences
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    • 제25권12호
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    • pp.1759-1767
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    • 2012
  • This study was performed to determine the effects of dietary fat sources, i.e., beef tallow, soybean oil, olive oil and coconut oil (each 3% in feed), on the growth performance, meat quality and gene expression in growing-finishing pigs. A total of 72 crossbred pigs (Landrace${\times}$Large White${\times}$Duroc) were used at $71{\pm}1$ kg body weight (about 130 d of age) in 24 pens ($320{\times}150$ cm) in a confined pig house (three pigs per pen) with six replicate pens per treatment. The growing diet was given for periods of $14{\pm}3$ d and the finishing diet was given for periods of $28{\pm}3$ d. The fat type had no significant effect either on growth performance or on chemical composition or on meat quality in growing-finishing pigs. Dietary fat type affected fatty acid composition, with higher levels of unsaturated fatty acids (UFAs) and monounsaturated fatty acids (MUFAs) in the olive oil group. Microarray analysis in the Longissimus dorsi identified 6 genes, related to insulin signaling pathway, that were differentially expressed among the different feed groups. Real time-PCR was conducted on the six genes in the longissimus dorsi muscle (LM). In particular, the genes encoding the protein kinase, cAMP-dependent, regulatory, type II, alpha (PRKAR2A) and the catalytic subunit of protein phosphatase 1, beta isoform (PPP1CB) showed the highest expression level in the olive oil group (respectively, p<0.05, p<0.001). The results of this study indicate that the type of dietary fat affects fatty acid composition and insulin signaling-related gene expression in the LM of pigs.

Differential Proteome Expression of in vitro Proliferating Hanwoo Stromal Vascular Cells from Omental, Subcutaneous and Intramuscular Depots in Response to Hormone Deprivation and IGF-1, Estradiol-17β Addition

  • Rajesh, Ramanna Valmiki;Kim, Seong-Kon;Park, Min-Ah;Kwon, Seulemina;Chang, Jong-Soo;Yoon, Du-Hak;Kim, Tae-Hun;Lee, Hyun-Jeong
    • Journal of Animal Science and Technology
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    • 제52권3호
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    • pp.175-186
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    • 2010
  • The aim of this study was to analyze the proteome expressions of proliferating stromal vascular cells from Hanwoo omental, subcutaneous and intramuscular depots subjected to hormone deprivation and IGF-1, Estradiol-$17{\beta}$ addition. For hormone deprivation or addition studies, the cells were either grown in 10% charcoal-dextran stripped fetal bovine serum (CD-FBS) or in 10% FBS supplemented medium. Further, to analyze the effect of insulin like growth factor (IGF-1) and $17\beta$-Estradiol (E2), cells were grown in 10% CD-FBS containing IGF-1 (10 ng/ml) or E2 (10 nM). The results showed that hormone deprivation had a negative impact on proliferation among the cells from all depots without any growth difference. On comparison of proliferation levels, higher levels were observed in cells that were grown in 10% FBS than in 10% CD-FBS alone or with IGF-1/E2. Proteome expression from preadipocytes grown in hormone deprivation conditions were compared by 2D-DIGE and MALDIToF/ToF. A total of twelve different proteins were found to be differentially expressed under hormone deprivation conditions. Further, our proteomic analysis with DIGE under IGF-1 and E2 addition revealed four proteins with differential expression levels. Moreover, the results highlighted in this study offer a role for each differentially expressed protein with respect to their effect in positive or negative regulation on proliferation.

전장 유전체 관련성 분석을 통한 한우 도체수율 관련 양적형질좌위 탐색 (Genome wide association test to identity QTL for dressing percentage in Hanwoo)

  • 이승환;임다정;당창권;장선식;김형철;전기준;연성흠;장길원;박응우;오재돈;이학교;이준헌;강희설;윤두학
    • 농업과학연구
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    • 제40권2호
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    • pp.155-162
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    • 2013
  • Genome-wide association study was performed on data from 266 Hanwoo steers derived from 66 sire using bovine 10K mapping chip in Hanwoo (Korean Cattle). SNPs were excluded from the analysis if they failed in over 5% of the genotypes, had median GC scores below 0.6, had GC scores under 0.6 in less than 90% of the samples, deviated in heterozygosity more than 3 standard deviations from the other SNPs and were out of Hardy-Weinberg equilibrium for a cutoff p-value of $1^{-15}$. Unmapped and SNPs on sex chromosomes were also excluded. A total of 4,522 SNPs were included in the analysis. To test an association between SNP and QTL, GWAS for five genetic mode (additive, dominant, overdominant, recessive and codominant) was implemented in this study. Three SNPs (rs29018694, ss46526851 and rs29018222) at a threshold p< $1.11{\times}10^{-5}$ were detected on BTA12 and BTA21 for dressing percentages in codominant and recessive genetic mode. The G allele for rs29018694 has 4.9% higher dressing percentage than A allele, while the T allele for ss46526851 has 2.57 % higher dressing percentage than C allele. Therefore, rs29018694 SNP showed a bigger effect than the other two SNPs (ss46526851 and rs29018222) in this study. In conclusion, this study identifies three loci with moderate effects and many loci with infinitesimally small effect across genome in Hanwoo.

Expression of Rice Chitinase Gene in Genetically Engineered Tomato Confers Enhanced Resistance to Fusarium Wilt and Early Blight

  • Jabeen, Nyla;Chaudhary, Zubeda;Gulfraz, Muhammad;Rashid, Hamid;Mirza, Bushra
    • The Plant Pathology Journal
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    • 제31권3호
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    • pp.252-258
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    • 2015
  • This is the first study reporting the evaluation of transgenic lines of tomato harboring rice chitinase (RCG3) gene for resistance to two important fungal pathogens Fusarium oxysporum f. sp. lycopersici (Fol) causing fusarium wilt and Alternaria solani causing early blight (EB). In this study, three transgenic lines TL1, TL2 and TL3 of tomato Solanum lycopersicum Mill. cv. Riogrande genetically engineered with rice chitinase (RCG 3) gene and their R1 progeny was tested for resistance to Fol by root dip method and A. solani by detached leaf assay. All the R0 transgenic lines were highly resistant to these fungal pathogens compared to nontransgenic control plants. The pattern of segregation of three independent transformant for Fol and A. solani was also studied. Mendelian segregation was observed in transgenic lines 2 and 3 while it was not observed in transgenic line 1. It was concluded that introduction of chitinase gene in susceptible cultivar of tomato not only enhanced the resistance but was stably inherited in transgenic lines 2 and 3.

3',4'-Dihydroxyl Groups in Luteolin are Important for Its Inhibitory Activities against ADAMTS-4

  • Choi, Ji-Won;Jeong, Ki-Woong;Kim, Jin-Kyoung;Chang, Byung-Ha;Lee, Jee-Young;Kim, Yang-Mee
    • Bulletin of the Korean Chemical Society
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    • 제33권9호
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    • pp.2907-2909
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    • 2012
  • A disintegrin and metalloprotease with thrombospondin domains (ADAMTS) are a member of peptidase and involved in processing of von Willebrand factor as well as cleavage of aggrecan, versican, brevican and neurocan. Among 19 subfamilies of human ADAMTS, ADAMTS-4 is a zinc-binding metalloprotease and is a famous therapeutic target for arthritis. It has been reported that a flavonoid luteolin shows inhibitory activity against ADMATS-4. In this study, we verified that luteolin is a potent inhibitor of ADAMTS-4 and probed the molecular basis of its action. On the basis of a docking study, we proposed a binding model between luteolin and ADAMTS-4 in which 3',4'-dihydroxyl groups in luteolin formed hydrogen bonding with ADMATS-4 and these interactions are important for its inhibitory activity against ADAMTS-4.