• 제목/요약/키워드: pleiotropic effects

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스타틴계 고지혈증치료제의 골절치료효과에 대한 분석 (Analysis on Statins for The Treatment of Bone Fracture)

  • 최병철
    • 약학회지
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    • 제53권4호
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    • pp.206-216
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    • 2009
  • 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (Statins) are potent inhibitors of cholesterol biosynthesis. Cholesterol-lowering therapy using statins significantly reduces the risk of coronary heart disease. Various discovery of statins as bone anabolic agents has spurred a great deal of interest among both basic and clinical bone researchers. In-vitro and some animal studies suggest that statins increase the bone mass by enhancing bone morphogenetic protein-2 (BMP-2)-mediated osteoblast expression. Clinical and animal test results of statins focusing on the prevention and treatment of bone fractures was collected. Three independent literature searches were performed by using from January 1, 2002 to September 2008 for clinical and animal test results. Search term included statins, HMG-CoA reductase inhibitors, pleiotropic effects, fracture, osteoporosis and clinical and animal test. No consensus has been reached whether clinical use of statins has beneficial effects on bone health, partly due to lower statin concentrations because of first-pass metabolism by the liver. Experimental use of statins as stimulators of bone formation suggests that they may have widespread applicability in the field of orthopaedics. With their combined effects on osteoblasts and osteoclasts, statins have the potential to enhance resorption of synthetic materials and improve bone ingrowth. In conclusion, The use of statins in the prevention and treatment of bone fractures requires further study. But observational studies suggest that statins for decreasing bone fractures including osteoporosis have to be considered local direct administration like transdermal or subcutaneous type over oral adminstration.

Elevated level of PLRG1 is critical for the proliferation and maintenance of genome stability of tumor cells

  • Hyunji Choi;Moonkyung Kang;Kee-Ho Lee;Yeon-Soo Kim
    • BMB Reports
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    • 제56권11호
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    • pp.612-617
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    • 2023
  • Pleiotropic regulator 1 (PLRG1), a highly conserved element in the spliceosome, can form a NineTeen Complex (NTC) with Prp19, SPF27, and CDC5L. This complex plays crucial roles in both pre-mRNA splicing and DNA repair processes. Here, we provide evidence that PLRG1 has a multifaceted impact on cancer cell proliferation. Comparing its expression levels in cancer and normal cells, we observed that PLRG1 was upregulated in various tumor tissues and cell lines. Knockdown of PLRG1 resulted in tumor-specific cell death. Depletion of PLRG1 had notable effects, including mitotic arrest, microtubule instability, endoplasmic reticulum (ER) stress, and accumulation of autophagy, ultimately culminating in apoptosis. Our results also demonstrated that PLRG1 downregulation contributed to DNA damage in cancer cells, which we confirmed through experimental validation as DNA repair impairment. Interestingly, when PLRG1 was decreased in normal cells, it induced G1 arrest as a self-protective mechanism, distinguishing it from effects observed in cancer cells. These results highlight multifaceted impacts of PLRG1 in cancer and underscore its potential as a novel anti-cancer strategy by selectively targeting cancer cells.

MOLECULAR CONTROLS OF EPIDERMAL GROWTH AND DIFFERENTIATION: TRANSFORMING GROWTH FACTORE

  • Son, Youngsook;Fuchs, Elaine
    • Toxicological Research
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    • 제7권2호
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    • pp.209-229
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    • 1991
  • In the epidermis of skin, a fine balance exists between proliferating progenitor cells and terminally differentiating cells. We examined the effects of TGF-betas and retinoic acid (RA) on controlling this balance in normal human epidermal keratinocytes cultured under conditions where most morphological and biochemical features of epidermis in vivo are retained. Our results revealed marked and pleiotropic effects of both TGF-beta and RA on kerationcytes. In contrast to retinoids, TGF-betas acted on mitotically active basal cells to retard cell proliferation.

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Comprehensive Expression Analysis Suggests Functional Overlapping of Human FOX Transcription Factors in Cancer

  • Zhang, Ya-Li;Sun, Feng-Ting;Zhang, Ze;Chen, Xiao-Xu;Liu, Ai-Xiang;Pan, Jing-Jing;Peng, Fei;Zhou, Shuai;Sun, Li-Jun
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권23호
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    • pp.10475-10481
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    • 2015
  • Forkhead-box (FOX) transcription factors comprise a large gene family that contains more than 50 members in man. Extensive studies have revealed that they not only have functions in control of growth and development, but also play important roles in different diseases, especially in cancer. However, biological functions for most of the members in the FOX family remain unknown. In the present study, the expression of 39 FOX genes in 48 kinds of cancer was mined from the Gene Expression Atlas database of European Bioinformatics Institute. The analysis results showed that some FOX genes demonstrate overlapping expression in various cancers, which suggests particular biological functions. The pleiotropic features of the FOX genes make them excellent candidates in efforts aimed to give medical treatment for cancers at the genetic level. The results also indicated that different FOX genes may have the synergy or antagonistics effects in the same cancers. The study provides clues for further functional analysis of FOX genes, especially for the pleiotropic biological functions and crosstalk of FOX genes in human cancers.

Switching Antibiotics Production On and Off in Actinomycetes by an IclR Family Transcriptional Regulator from Streptomyces peucetius ATCC 27952

  • Chaudhary, Amit Kumar;Singh, Bijay;Maharjan, Sushila;Jha, Amit Kumar;Kim, Byung-Gee;Sohng, Jae Kyung
    • Journal of Microbiology and Biotechnology
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    • 제24권8호
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    • pp.1065-1072
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    • 2014
  • Doxorubicin, produced by Streptomyces peucetius ATCC 27952, is tightly regulated by dnrO, dnrN, and dnrI regulators. Genome mining of S. peucetius revealed the presence of the IclR (doxR) type family of transcription regulator mediating the signal-dependent expression of operons at the nonribosomal peptide synthetase gene cluster. Overexpression of doxR in native strain strongly repressed the drug production. Furthermore, it also had a negative effect on the regulatory system of doxorubicin, wherein the transcript of dnrI was reduced to the maximum level in comparision with the other two. Interestingly, the overexpression of the same gene also had strong inhibitory effects on the production of actinorhodin (blue pigment) and undecylprodigiosin (red pigment) in Streptomyces coelicolor M145, herboxidiene production in Streptomyces chromofuscus ATCC 49982, and spinosyn production in Saccharopolyspora spinosa NRRL 18395, respectively. Moreover, DoxR exhibited pleiotropic effects on the production of blue and red pigments in S. coelicolor when grown in different agar media, wherein the production of blue pigment was inhibited in R2YE medium and the red pigment was inhibited in YEME medium. However, the production of both blue and red pigments from S. coelicolor harboring doxR was halted in ISP2 medium, whereas S. coelicolor produced both pigmented antibiotics in the same plate. These consequences demonstrate that the on and off production of these antibiotics was not due to salt stress or media compositions, but was selectively controlled in actinomycetes.

Pleiotropic Effects of Caffeine Leading to Chromosome Instability and Cytotoxicity in Eukaryotic Microorganisms

  • Chung, Woo-Hyun
    • Journal of Microbiology and Biotechnology
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    • 제31권2호
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    • pp.171-180
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    • 2021
  • Caffeine, a methylxanthine analog of purine bases, is a compound that is largely consumed in beverages and medications for psychoactive and diuretic effects and plays many beneficial roles in neuronal stimulation and enhancement of anti-tumor immune responses by blocking adenosine receptors in higher organisms. In single-cell eukaryotes, however, caffeine somehow impairs cellular fitness by compromising cell wall integrity, inhibiting target of rapamycin (TOR) signaling and growth, and overriding cell cycle arrest caused by DNA damage. Among its multiple inhibitory targets, caffeine specifically interacts with phosphatidylinositol 3-kinase (PI3K)-related kinases causing radiosensitization and cytotoxicity via specialized intermediate molecules. Caffeine potentiates the lethality of cells in conjunction with several other stressors such as oxidants, irradiation, and various toxic compounds through largely unknown mechanisms. In this review, recent findings on caffeine effects and cellular detoxification schemes are highlighted and discussed with an emphasis on the inhibitory interactions between caffeine and its multiple targets in eukaryotic microorganisms such as budding and fission yeasts.

Association Analysis of Charcoal Rot Disease Resistance in Soybean

  • Ghorbanipour, Ali;Rabiei, Babak;Rahmanpour, Siamak;Khodaparast, Seyed Akbar
    • The Plant Pathology Journal
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    • 제35권3호
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    • pp.189-199
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    • 2019
  • In this research, the relationships among the 31 microsatellite markers with charcoal rot disease resistance related indices in 130 different soybean cultivars and lines were evaluated using association analysis based on the general linear model (GLM) and the mixed linear model (MLM) by the Structure and Tassel software. The results of microsatellite markers showed that the genetic structure of the studied population has three subpopulations (K=3) which the results of bar plat also confirmed it. In association analysis based on GLM and MLM models, 31 and 35 loci showed significant relationships with the evaluated traits, respectively, and confirmed considerable variation of the studied traits. The identified markers related to some of the studied traits were the same which can probably be due to pleiotropic effects or tight linkage among the genomic regions controlling these traits. Some of these relationships were including, the relationship between Sat_252 marker with amount of charcoal rot disease, Satt359, Satt190 and Sat_169 markers with number of microsclerota in stem, amount of charcoal rot disease and severity of charcoal rot disease, Sat_416 marker with number of microsclerota in stem and amount of charcoal rot disease and the Satt460 marker with number of microsclerota in stem and severity of charcoal rot disease. The results of this research and the linked microsatellite markers with the charcoal rot disease-related characteristics can be used to identify the suitable parents and to improve the soybean population in future breeding programs.

교감신경계가 암의 발전과 진행에 미치는 영향 (The Influence of the Sympathetic Nervous System on the Development and Progression of Cancer)

  • 박신형;지규용;최영현
    • 생명과학회지
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    • 제28권1호
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    • pp.116-129
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    • 2018
  • 생물체는 스트레스에 대처하기 위한 항상성 유지 기작을 가지고 있으나, 만성적이고 반복적인 스트레스는 카테콜아민과 같은 스트레스 호르몬의 과도한 방출로 인해 인체에 해로운 영향을 미친다. 교감신경계와 암과의 관련성을 분석하는 연구는 스트레스가 암을 악화시킬 수 있다는 오랜 가설을 바탕으로 이루어졌다. 다수의 전임상연구와 역학 연구결과는 교감신경계의 주요 신호전달경로인 ${\beta}$-adrenergic signaling을 조절하는 것이 암의 진행을 억제할 수 있음을 보여주고 있다. 교감신경계의 활성화는 암세포의 oncogene과 DNA repair 유전자 조절, 생존과 사멸 조절, EMT 및 전이 조절, 면역계와 혈관신생 조절, 세포외기질과 간엽세포 조절, 지방세포 조절 등을 통해 암세포와 종양미세환경에 광범위하게 영향을 미칠 수 있다. 오늘날 암의 성장과 관련된 분자적 기전을 차단하는 표적항암치료가 각광받고 있으나, 보상경로의 활성화와 항암제 내성 출현 및 여러 부작용으로 말미암아 임상적 실패를 거듭하면서 암의 생병리를 다방면에서 조절하는 전략이 새로운 치료법으로 대두되고 있다. 본 총설에서는 이러한 암의 전신적 조절인자로서 교감신경계가 암의 형성과 발전에 미치는 영향을 요약하고, 향후 새로운 암 치료전략으로서 ${\beta}$-adrenergic signaling을 조절하는 약물의 임상적 활용가능성에 대해 논의하고자 한다.

Whole Genome Association Study to Detect Single Nucleotide Polymorphisms for Body Conformation Traits in a Hanwoo Population

  • Alama, M.;Lee, Y.M.;Park, B.L.;Kim, J.H.;Lee, S.S.;Shin, H.D.;Kim, K.S.;Kim, N.S.;Kim, J.J.
    • Asian-Australasian Journal of Animal Sciences
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    • 제24권3호
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    • pp.322-329
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    • 2011
  • A whole genome association (WGA) study was conducted to identify quantitative trait loci (QTL) for body conformation traits in Hanwoo cattle. The phenotypes of 497 steers were recorded from the Hanwoo Improvement Center of National Agricultural Cooperative Federation, Seosan, Korea, and analyzed using the Illumina Bovine 50 k SNP chip. A set of 35,987 SNPs that were available in the Hanwoo population was selected from the chip. After adjustments for the effects of year-season of birth, region and sire, phenotypes were regressed on each SNP using a linear regression model. Three hundred nineteen SNPs were detected for the ten conformation traits (p<0.003). For the significant SNPs, stepwise regression procedures were applied to determine best sets of markers. A total of 72 SNPs were selected (p<0.001), for which the sets of 5, 9, 10, 9, 8, 11, 4, 6, 3 and 7 SNPs were determined for height at withers, rump height, body length, chest depth, chest width, rump length, hip width, thurl width, pinbone width and heart girth, respectively. About 7-26% of the total phenotypic variation was explained by the set of SNPs for each trait. QTL for the conformation traits were harbored on most bovine chromosomes (BTAs). Four SNPs with pleiotropic effects on height at withers and rump height were detected on BTAs 3, 4, 6 and 16. A SNP with pleiotropic effects on chest width and rump length was also detected on BTA10. Two QTL regions, i.e. between 87 and 97 Mb in BTA3 and between 41 and 44 Mb in BTA7, were found, in which SNPs were detected for the five and three conformation traits, respectively. The detected SNPs need to be validated in other Hanwoo populations for commercial application to the genetic improvement of conformation characteristics in Hanwoo via marker-assisted selection (MAS).