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1
Yi, Xie, and Li Bing. "The Transcription Express Characteristics of Several Genes in the Process of Bombyx mori Ovarian Carcinoma." Advanced Materials Research 796 (September 2013): 39–42. http://dx.doi.org/10.4028/www.scientific.net/amr.796.39.
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Bombyx mori cell line (BmN) comes fromBombyx moriovary cell subculture. In order to study the change of several genes transcription in the process ofBombyx moriovary cells primary culture and subculture, we usedBombyx moriovary organizations and BmN cell lines as research materials, used Real Time fluorescent quantitative RT-PCR to detect cyclin gene family (CyclinA, CyclinB, CyclinB3, CyclinE, CyclinL1), p53 and Telomerase genes transcription level in the ovary and BmN cell lines, and took Actin3 gene as reference to dispose the results. The results showed that in theBombyx moriBmN cell lines the expression of CyclinA, CyclinB, CyclinB3, CyclinE, CyclinL1 and Telomerase genes were higher than those in the ovary. The expression of CyclinB in the BmN was more then 3.8 which was 76 times higher than that in the ovary; The expression of p53 gene in the BmN cell was lower than that in the ovary; The expression of Telomerase gene in the BmN cell was higher than that in the ovary. The results accumulated a reliable data for further study on the the role of cyclin gene family, p53 gene, and Telomerase gene in the process ofBombyx moriovarian carcinoma.
2
Buchkovich, K. J., and E. B. Ziff. "Nerve growth factor regulates the expression and activity of p33cdk2 and p34cdc2 kinases in PC12 pheochromocytoma cells." Molecular Biology of the Cell 5, no. 11 (November 1994): 1225–41. http://dx.doi.org/10.1091/mbc.5.11.1225.
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In the absence of serum, nerve growth factor (NGF) promotes the survival and differentiation of the PC12 pheochromocytoma cell line. In the presence of serum, NGF acts primarily as a differentiation factor and negative regulator of cell cycling. To investigate NGF control of cell cycling, we have analyzed the regulation of cyclin dependent kinases during PC12 cell differentiation. NGF treatment leads to a reduction in the steady-state protein levels of p33cdk2 and p34cdc2, two key regulators of cell cycle progression. The decrease in p33cdk2 and p34cdc2 coincides with a decrease in the enzymatic activity of cyclinA-p34cdc2, cyclinB-p34cdc2, cyclinE-p33cdk2, and cyclinA-p33cdk2 kinases. The decline in p33cdk2 and p34cdc2 kinase activity in response to NGF is accelerated in cells that over-express the p140trk NGF receptor, suggesting that the timing of the down- regulation is dependent on the level of p140trk and the strength of the NGF signal. The level of cyclin A, a regulatory subunit of p33cdk2 and p34cdc2, is relatively constant during PC12 differentiation. Nevertheless, the DNA binding activity of the cyclinA-associated transcription factor E2F/DP decreases. Thus, NGF down-regulates the activity of cyclin dependent kinases and cyclin-transcription factor complexes during PC12 differentiation.
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Сальков, Николай, and Nikolay Sal'kov. "Representations of Dupin Cyclides." Geometry & Graphics 5, no. 3 (September 28, 2017): 11–24. http://dx.doi.org/10.12737/article_59bfa354466be1.50763524.
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We know very little about such an interesting surface as Dupin cyclide. It belongs to channel surfaces, its special cases are tor, conical and cylindrical surfaces of rotation. It is known that Dupin cyclides are the only surfaces whose focal surfaces, that are surfaces consisting of sets of curvatures centers points, have been degenerated in second-order curves. Two sets give two confocal conics. That is why any study of Dupin cyclides is of great interest both scientific and applied. In the works devoted to Dupin cyclide and published in the "Geometry and Graphics" journal, are presented various properties of cyclides, and demonstrated application of these surfaces in various industries, mostly in construction. Based on the cyclides’ properties in 1980s have been developed numerous inventions relating to devices for drawing and having the opportunity to be applied in various geometric constructions with the use of computer technologies. In the present paper have been considered various options for representation of Dupin cyclides on a different basis – from the traditional way using the three given spheres unto the second-order curves. In such a case, if it is possible to represent four cyclides by three spheres, and when cyclide is represented by the second-order curve (konic) and the sphere their number is reduced to two, then in representation of cyclide by the conic and one of two cyclide’s axes a single Dupin cyclide is obtained. The conic itself without any additional parameters represents the single-parameter set of cyclides. Representations of Dupin cyclides by ellipse, hyperbola and parabola have been considered. The work has been sufficiently illustrated.
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Belbis, Bertrand, Lionel Garnier, and Sebti Foufou. "Construction of 3D Triangles on Dupin Cyclides." International Journal of Computer Vision and Image Processing 1, no. 2 (April 2011): 42–57. http://dx.doi.org/10.4018/ijcvip.2011040104.
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This paper considers the conversion of the parametric Bézier surfaces, classically used in CAD-CAM, into patched of a class of non-spherical degree 4 algebraic surfaces called Dupin cyclides, and the definition of 3D triangle with circular edges on Dupin cyclides. Dupin cyclides was discovered by the French mathematician Pierre-Charles Dupin at the beginning of the 19th century. A Dupin cyclide has one parametric equation, two implicit equations, and a set of circular lines of curvature. The authors use the properties of these surfaces to prove that three families of circles (meridian arcs, parallel arcs, and Villarceau circles) can be computed on every Dupin cyclide. A geometric algorithm to compute these circles so that they define the edges of a 3D triangle on the Dupin cyclide is presented. Examples of conversions and 3D triangles are also presented to illustrate the proposed algorithms.
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Garnier, Lionel, Lucie Druoton, Jean-Paul Bécar, Laurent Fuchs, and Géraldine Morin. "Subdivisions of Ring Dupin Cyclides Using Bézier Curves with Mass Points." WSEAS TRANSACTIONS ON MATHEMATICS 20 (November 9, 2021): 581–97. http://dx.doi.org/10.37394/23206.2021.20.62.
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The paper deals in the Computer-Aided Design or Computer-Aided Manufacturing domain with the Dupin cyclides as well as the Bézier curves. It shows that the same algorithms can be used either for subdivisions of ring Dupin cyclides or Bézier curves. The Bézier curves are described with mass points here. The Dupin cyclides are considered in the Minkowski-Lorentz space. This makes a Dupin cyclide as the union of two conics on the unit pseudo-hypersphere, called the space of spheres. And the conics are quadratic Bézier curves modelled by mass points. The subdivision of any Dupin cyclide, is equivalent to subdivide two curves of degree 2, independently, whereas in the 3D Euclidean space, the same work implies the subdivision of a rational quadratic Bézier surface and resolutions of systems of three linear equations. The first part of this work is to consider ring Dupin cyclides because the conics are bounded circles which look like ellipses.
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Srinivas, Y. L., and Debashish Dutta. "Cyclides in Geometric Modeling: Computational Tools for an Algorithmic Infrastructure." Journal of Mechanical Design 117, no. 3 (September 1, 1995): 363–73. http://dx.doi.org/10.1115/1.2826689.
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The Dupin cyclide is a quartic surface with useful properties such as circular lines of curvature, rational parametric representations and closure under offsetting. All natural quadrics (cone, cylinder, sphere) and the torus are special cases of the cyclide. Applications of cyclides include variable radius blending, piping design and design of tubular geometry, such as mold gates and wire harnesses. While the mathematical treatment of cyclides is well developed, the tools required to incorporate this surface into conventional modeling applications have not received sufficient attention. In this paper, we detail various methods for manipulating and computing with the cyclide. Issues such as auxiliary representations, inverse parameter mapping, point classification, normal projection of a point onto the surface, distance computation, bounding volumes and surface intersection detection are discussed in detail. We also provide implemented examples of design applications that utilize these computational tools.
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Сальков and Nikolay Sal'kov. "Properties of Dupin Cyclide and Their Application. Part 4: Applications." Geometry & Graphics 4, no. 1 (March 17, 2016): 21–33. http://dx.doi.org/10.12737/18055.
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In the first and second parts of the work there were
considered mainly properties of Dupin cyclide, and given some
examples of their application: three ways of solving the problem of
Apollonius using only compass and ruler, using the identified properties
of cyclide; it is determined that the focal surfaces of Dupin
cyclid are degenerated in the lines and represent curves of the
second order – herefrom Dupin cyclide can be defined by conic curve and a sphere whose center lies on the focal curve. Polyconic
compliance of these focal curves is identified. The formation of the
surface of the fourth order on the basis of defocusing curves of the
second order is shown.
In this issue of the journal the reader is invited to consider the
practical application of Dupin cyclide’s properties. The proposed
solution of Fermat’s classical task about the touch of the four
spheres by the fifth with a ruler and compass, i.e., in the classical
way. This task is the basis for the problem of dense packing. In the
following there is an application of Dupin cyclide as a transition
pipe element, providing smooth coupling of pipes of different diameters
in places of their connections. Then the author provides
the examples of Dupin cyclide’s application in the architecture as
a shell coating. It is shown how to produce membranes from the
same cyclide’s modules, from different modules of the same cyclide,
from the modules of different cyclides, from cyclides with the inclusion
of other surfaces, special cases of cyclides in the educational
process. The practical application of the last problem found the
place in descriptive geometry at the final geometrical education of
architects in the "Construction of surfaces". Here such special cased
of cyclides as conical and cylindrical surfaces of revolution.
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Sun, Lu, Yan Pan, Xiaochun Wang, Gang Gao, Lina Wu, Chunnan Piao, Jianlei Ruan, and Jianxiang Liu. "Screening for Potential Biomarkers in Peripheral Blood From Miners Exposed to Radon Radiation." Dose-Response 18, no. 1 (January 1, 2020): 155932582090460. http://dx.doi.org/10.1177/1559325820904600.
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In this cohort study of 144 miners, 72 miners worked underground (the study group) and 72 miners worked aboveground (the control group). Based on questionnaire data and of radon concentration measurements, the cumulative radon exposure dose was calculated for each miner using the parameters recommended in International Commission on Radiological Protection Publication 137. Hematological parameters such as lymphocyte count (LYM) and neutrophil count (NE) were assessed, cell cycle phases and regulatory proteins were detected by flow cytometry, and microRNA (miRNA) microarray screening and real-time polymerase chain reaction (PCR) were used to detect miRNAs in plasma. The interrelationships between various potential biomarkers were analyzed using bioinformatics and statistical methods. The mean cumulative exposure dose of underground miners and controls was 982 and 48 mSv, respectively. Hematological parameters (such as LYM and NE) were significantly lower in the underground group. Cyclin-dependent kinase (CDK)-2, CDK4, CDK6, CyclinA2, CyclinD1, and CyclinE1 were significantly higher in the underground group. MicroRNA microarray screening showed that 5 miRNAs were downregulated (fold-change >2) in the underground group. The real-time PCR detection results of miR-19a, miR-30e, miR-335, and miR-451a were consistent with the screening results. LYM, NE, CDK2, CDK4, CDK6, Cyclin A2, Cyclin D1, Cyclin E1, miR-19a, miR-30e, miR-335, and miR451a are potential biomarkers of radon radiation damage.
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Garnier, Lionel, Lucie Druoton, Jean-Paul Bécar, Laurent Fuchs, and Géraldine Morin. "Subdivisions of Horned or Spindle Dupin Cyclides Using Bézier Curves with Mass Points." WSEAS TRANSACTIONS ON MATHEMATICS 20 (December 31, 2021): 756–76. http://dx.doi.org/10.37394/23206.2021.20.80.
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This paper shows the same algorithm is used for subdivisions of Dupin cyclides with singular points and quadratic Bézier curves passing through infinity. The mass points are usefull for any quadratic Bézier representation of a parabola or an hyperbola arc. The mass points are mixing weighted points and pure vectors. Any Dupin cyclide is considered in the Minkowski-Lorentz space. In that space, the Dupin cyclide is defined by the union of two conics laying on the unit pseudo-hypersphere, called the space of spheres. The subdivision of any Dupin cyclide, is equivalent to subdivide two Bézier curves of degree 2 with mass points, independently. The use of these two curves eases the subdivision of a Dupin cyclide patch or triangle.
10
Srinivas, Y. L., and D. Dutta. "Blending and Joining Using Cyclides." Journal of Mechanical Design 116, no. 4 (December 1, 1994): 1034–41. http://dx.doi.org/10.1115/1.2919484.
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We consider the use of Dupin cyclides in geometric modeling. These are algebraic surfaces of degree four with interesting properties such as rational parametric forms and closure under offsets. We have been focusing on methods for expanding the geometric coverage of solid modelers, and the cyclide as a new primitive offers promise. In this paper, we briefly describe the cyclide and discuss in details two applications. The first is the modeling of blending surfaces, an important problem in geometric modeling. We outline methods to use various forms of the cyclide in variable-radius blending. Next, we consider the problem of automatic joining of pipes, and describe a general method rooted in the definition of a cyclide for its solution. Implemented examples are provided for both applications.
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Xie, Jing, Ming-Rong Yang, Xia Hu, Zi-Shan Hong, Yu-Ying Bai, Jun Sheng, Yang Tian, and Chong-Ying Shi. "Moringa oleifera Lam. Isothiocyanate Quinazolinone Derivatives Inhibit U251 Glioma Cell Proliferation through Cell Cycle Regulation and Apoptosis Induction." International Journal of Molecular Sciences 24, no. 14 (July 12, 2023): 11376. http://dx.doi.org/10.3390/ijms241411376.
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A major active constituent of Moringa oleifera Lam. is 4-[(α-L-rhamnose oxy) benzyl] isothiocyanate (MITC). To broaden MITC’s application and improve its biological activity, we synthesized a series of MITC quinazolinone derivatives and evaluated their anticancer activity. The anticancer effects and mechanisms of the compound with the most potent anticancer activity were investigated further. Among 16 MITC quinazolinone derivatives which were analyzed, MITC-12 significantly inhibited the growth of U251, A375, A431, HCT-116, HeLa, and MDA-MB-231 cells. MITC-12 significantly inhibited U251 cell proliferation in a time- and dose-dependent manner and decreased the number of EdU-positive cells, but was not toxic to normal human gastric mucosal cells (GES-1). Further, MITC-12 induced apoptosis of U251 cells, and increased caspase-3 expression levels and the Bax:Bcl-2 ratio. In addition, MITC-12 significantly decreased the proportion of U251 cells in the G1 phase and increased it in S and G2 phases. Transcriptome sequencing showed that MITC-12 had a significant regulatory effect on pathways regulating the cell cycle. Further, MITC-12 significantly decreased the expression levels of the cell cycle-related proteins CDK2, cyclinD1, and cyclinE, and increased those of cyclinA2, as well as the p-JNK:JNK ratio. These results indicate that MITC-12 inhibits U251 cell proliferation by inducing apoptosis and cell cycle arrest, activating JNK, and regulating cell cycle-associated proteins. MITC-12 has potential for use in the prevention and treatment of glioma.
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Ehrhardt, Harald, Catarina Castro Alves, Franziska Wachter, and Irmela Jeremias. "TRAIL Preferentially Affects Cell Cycle-Arrested Tumor Cells Including Stem- and Progenitor Cells From Patients with Acute Lymphoblastic Leukemia." Blood 120, no. 21 (November 16, 2012): 1879. http://dx.doi.org/10.1182/blood.v120.21.1879.1879.
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Abstract Abstract 1879 Leukemic stem- and progenitor cells exhibit low cycling activity which might represent a major cause for their increased treatment resistance. TRAIL (TNF-related apoptosis inducing ligand) is a novel putative anticancer drug currently in phase I and II clinical testing. We recently showed that TRAIL is able to address stem- and progenitor cells from patients with acute lymphoblastic leukemia (ALL) in xenotransplantation assays (Alves et al., Blood 2012,119,4224). As stem- and progenitor cells are often non-cycling, we asked here, whether TRAIL is able to address resting leukemia cells. We used cell lines and primary tumor cells from children with ALL which were amplified in severely immuno-compromised mice (NSG mice). Cell cycle arrest was induced (i) by addition of conventional cytotoxic drugs which are known to act as cytostatic drugs such as doxorubicine; (ii) by biochemical inhibitors known to induce cell cycle arrest at different defined points of the cell cycle such as mimosine; (iii) by molecular approaches and knockdown of cyclinB arresting cell cycle in G2 or knockdown of cyclinE arresting cell cycle in G1. Unexpectedly, TRAIL-induced apoptosis was enhanced, whenever cell cycle was arrested. Cell cycle arrest sensitized towards TRAIL-induced apoptosis independently from the point or phase of cell cycle which was arrested (G0, G1 or G2) and independently from the agent used to arrest the cell cycle. Similarly, knockdown of cyclinB or cyclinE both clearly sensitized cell line cells towards TRAIL-induced apoptosis. Cytotoxic drugs and cell cycle inhibitors might arrest the cell cycle by activation of p53. Accordingly, when caffeine was added which inhibited p53 activity and drug-induced cell cycle arrest, sensitization towards TRAIL-induced apoptosis was blocked. We have recently established a novel method which enables performing knockdown experiments in tumor cells derived from ALL patients (Höfig et al., Cell Comm. Signal. 2012,10,8). Using this method and most important for clinical translation, we could show that knockdown of either cyclinB or cyclinE clearly sensitized patient-derived ALL cells towards TRAIL-induced apoptosis. Taken together and in contrast to most conventional cytotoxic drugs, TRAIL exerts anti-tumor activity preferentially against tumor cells in cell cycle arrest and less against actively cycling tumor cells. This special feature of TRAIL might explain its anti-tumor activity against stem- and progenitor cells in patients with ALL. Thus, TRAIL might represent an interesting drug to treat disease stages with accumulation of stem- and progenitor cells and static tumor disease, e.g., during minimal residual disease. Disclosures: No relevant conflicts of interest to declare.
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Wang, Jubo, Yu Quan, Jian Lv, Quan Dong, and Shouping Gong. "LncRNA IDH1-AS1 suppresses cell proliferation and tumor growth in glioma." Biochemistry and Cell Biology 98, no. 5 (October 2020): 556–64. http://dx.doi.org/10.1139/bcb-2019-0465.
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Glioma is a type of brain tumor that is common globally, and is associated with a variety of genetic changes. It has been reported that isocitrate dehydrogenase 1 (IDH1) is overexpressed in glioma and in HeLa cells. The lncRNA IDH1-AS1 is believed to interact with IDH1, and when IDH1-AS1 is overexpressed, HeLa cell proliferation is inhibited. However, the effects of IDH1-AS1 on glioma were relatively unknown. The results from this work show that IDH1-AS1 is downregulated in the glioma tissues. We used primary glioblastoma cell lines U251 and U87-MG to study the effects of IDH1-AS1 on glioma cell growth, in vitro and in vivo. We found that when IDH1-AS1 is overexpressed cell proliferation is inhibited, cell cycle is arrested at the G1 phase, and the protein expression levels of cyclinD1, cyclinA, cyclinE, CDK2, and CDK4 are decreased. We found that cell apoptosis was increased when IDH1-AS1 was overexpressed, as evidenced by increases in the levels of cleaved caspase-9 and -3. Conversely, knockdown of IDH1-AS1 promoted cell proliferation. Moreover, we proved that overexpression of IDH1-AS1 inhibits the tumorigenesis of U251 cells, in vivo. Furthermore, IDH1-AS1 did not affect IDH1 protein expression, but altered its enzymatic activities in glioma cells. Silencing of IDH1 reversed the effects of IDH1-AS1 upregulation on cell viability. Hence, our study provides first-hand evidence for the effects of lncRNA IDH1-AS1 on gliomas. Because overexpressing IDH1-AS1 inhibited cell growth, IDH1-AS1 could also be considered as a potential target for glioma treatment.
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Сальков, Николай, and Nikolay Sal'kov. "Application of Dupin Cyclide’s Properties to Inventions." Geometry & Graphics 5, no. 4 (December 13, 2017): 37–43. http://dx.doi.org/10.12737/article_5a17fd233418b2.84489740.
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Dupin cyclide belongs to channel surfaces. These surfaces are the single known ones whose focal surfaces, i.e. surfaces consisting of point sets of centers of curvatures, have been degenerated into two confocal second order curves. In the works devoted to Dupin cyclide and published in the "Geometry and Graphics" journal, are presented various cyclides’ properties and demonstrated application of these surfaces in various industries, mostly in construction. Based on Dupin cyclides’ properties have been developed several inventions relating to drawing devices and having the opportunity to apply in various geometric constructions with the use of computer technologies. It is possible because the Dupin cyclides’ geometric properties suppose not only to create devices recognized as inventions, but also provide an opportunity to apply these properties to write programs for drawing v arious kinds of curves on a display screen: the second order curves, their equidistant in the direction of normals or tangents, as well as to perform other constructions. It should be said that in inventions belonging to technical areas, which include the drawing devices, the geometric component is always decisive. This position with the express aim of technical inventions can justify any copyright certificate of the USSR, any patent of Russia and foreign countries. Unfortunately, currently in schools geometry is not studied as a component of pupil’s intellectual horizons, that broadens his area of interests and teaches to analytical understanding the world, but as an inevitable, almost unnecessary appendage in preparation for the Unified State Examination.
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Garnier, Lionel, Lucie Druoton, Jean-Paul Bécar, Laurent Fuchs, and Géraldine Morin. "Mass Points, Spaces of Spheres, ”hyperbolae” and Dandelin and Quételet Theorems." WSEAS TRANSACTIONS ON MATHEMATICS 21 (May 31, 2022): 285–302. http://dx.doi.org/10.37394/23206.2022.21.34.
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The use of mass points eases the definition of a branch of a hyperbola in the Euclidean plane based on a Rational Quadratic Bézier Curve. In the space of spheres, any circular cone, circular cylinder, torus, pencil of spheres or Dupin cyclide is represented by a rational quadratic Bézier curve that is conic arc seen as circle arc. The limit points of the Poncelet pencil or the singular points of the Dupin cyclide can be determined using the asymptotes of this circle. This article shows that the use of mass points simplifies the modelling of these pencils or these Dupin cyclides in the space of spheres. The determination of the Dandelin spheres ends this work as an application.
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Zhang, Demei, Rui Wang, Shijian Han, Zhigang Li, Jiming Xiao, Yangrui Li, Lingqiang Wang, and Suli Li. "Transcriptome Analysis of between Sugarcane Young Leaves and Protoplasts after Enzymatic Digestion." Life 12, no. 8 (August 9, 2022): 1210. http://dx.doi.org/10.3390/life12081210.
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Sugarcane somatic cell hybridization can break through the barrier of genetic incompatibility between distantly related species in traditional breeding. However, the molecular mechanisms of sugarcane protoplast regeneration and the conditions for protoplast preparation remain largely unknown. In this study, young sugarcane (ROC22) leaves were enzymatically digested, and the viability of protoplasts reached more than 90% after enzymatic digestion (Enzymatic combination: 2% cellulase + 0.5% pectinase + 0.1% dissociative enzyme + 0.3% hemicellulase, pH = 5.8). Transcriptome sequencing was performed on young sugarcane leaves and protoplasts after enzymatic digestion to analyze the differences in gene expression in somatic cells before and after enzymatic digestion. A total of 117,411 unigenes and 43,460 differentially expressed genes were obtained, of which 21,123 were up-regulated and 22,337 down-regulated. The GO terms for the 43,460 differentially expressed genes (DEGs) were classified into three main categories: biological process, cellular component and molecular function, which related to developmental process, growth, cell proliferation, transcription regulator activity, signal transducer activity, antioxidant activity, oxidative stress, kinase activity, cell cycle, cell differentiation, plant hormone signal transduction, and so on. After enzymatic digestion of young sugarcane leaves, the expressions of GAUT, CESA, PSK, CyclinB, CyclinA, CyclinD3 and cdc2 genes associated with plant regeneration were significantly down-regulated to 65%, 47%, 2%, 18.60%, 21.32%, 52% and 45% of young leaves, respectively. After enzymatic digestion, Aux/IAA expression was up-regulated compared with young leaves, and Aux/IAA expression was 3.53 times higher than that of young leaves. Compared with young leaves, these key genes were significantly changed after enzymatic digestion. These results indicate that the process of somatic enzymatic digestion process may affect the regeneration of heterozygous cells to a certain extent.
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Minegishi, Naoko, Hideo Harigae, and Masayuki Yamamoto. "Bidirectional Control of Transcription Factor GATA2 and Cyclin/Cdks in Hematopoietic Cells." Blood 112, no. 11 (November 16, 2008): 1382. http://dx.doi.org/10.1182/blood.v112.11.1382.1382.
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Abstract GATA2 is a transcription factor indispensable for development and maintenance of hematopoietic stem cells. Hematopoietic stem cells in G0 phase express GATA2 (Suzuki N, PNAS 103: 2202 2006), but proliferating hematopoietic progenitor cells, as well as proliferating cells in several other tissues, also express this factor. Gata2 knockout experiments indicate that GATA2 regulates cell proliferation; however, precise mechanisms have not been elucidated. Previously, we found oscillatory expressions of GATA2 during the cell cycle. In G1/S and G2/M phases, Cdk4 and Cdk2, forming complexes with several cyclins, phosphorylate GATA2 and induce GATA2 degradation (Koga S, Blood109: 4200, 2007). In this study, we demonstrate the bidirectional control between GATA2 and Cyclin/Cdk systems. To identify GATA2 target genes regulating cell proliferation, we searched for conserved GATA factor-binding sequences in evolutionarily conserved regions (ECRs, http://ecrbrowser.dcode.org), and found conserved GATA sequences in ECRs in intron 3 and intron 4 of the CyclinD2 (Ccnd2) gene, and in intron 3 and 3′UTR of the CyclinE1 (Ccne1) gene. In ChIP experiments using synchronized Ba/F3 and P815 cells, GATA2 binding to these regions was high in late G1 phase, and then rapidly declined in early S phase. One hour treatment using a Cdk1/2 inhibitor, roscovitine, cancelled this regression in early S phase, implicating Cdk2 as a negative regulator of GATA2 binding to target genes. Significant GATA2 binding to Ccnd2 and Ccne1 genes was also detected in embryonic day 13.5 fetal liver cells. Exogenous GATA2 expression augmented transcriptional activity of these binding regions in luciferase assay. Induction of GATA2 siRNA repressed Ccnd2 and Ccne1 mRNA expression. Furthermore, Ccnd2 and Ccne1 mRNA expression, as well as Gata2 mRNA expression, was significantly reduced in placental and aortic regions of embryonic day 10.0 conceptihar boring insertions of green fluorescent protein cDNA at translation start sites of bothGata2 alleles (Minegishi N, Blood102: 896, 2003). These results indicate that Ccnd2 andCcne1 genes are direct targets of GATA2. GATA2 binds to Ccnd2 and Ccne1 genes and activates their transcription in the G1 phase of proliferating cells. In G1/S transition, Cdk2activity, probably enhanced by CyclinE1 expression, attenuate GATA2 binding to Ccnd2and Ccne1 genes. In this fashion, bidirectional control of GATA2 and G1 cyclins may contribute to the transient expression of CyclinD2 and CyclinE1 in G1 phase, and to the acceleration of S-phase entry. In addition, it appears plausible that lack of Cdk activities causes differences in GATA2 functions in hematopoietic stem cells in G0 phase.
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Wang, Xiaohui, Yidong Li, Xiaoyan Zhu, Yan Wang, Fei Diao, and Jian Lu. "Signal regulatory protein α1 is involved in the inhibitory effect of glucocorticoid receptor on the proliferation of murine macrophage RAW264.7 cell and mouse peritoneal macrophage." Journal of Molecular Endocrinology 41, no. 5 (August 26, 2008): 393–403. http://dx.doi.org/10.1677/jme-08-0021.
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Glucocorticoid (GC) effectively suppresses immune and inflammatory responses and inhibits the growth of several types of cells, but the role of GC and its receptor on macrophage proliferation is unclear. In our previous work, we found RAW-GR(−) cells (murine macrophage RAW264.7 cells stably transfected with GR-siRNA expression vector by RNA interference) grew faster by about twofold. In this study, we further explored the role and mechanisms of GC/GR on the proliferation of macrophage. We found that the growth of RAW264.7 cells was inhibited by dexamethasone (Dex) in a concentration-dependent manner. The mRNA and protein levels of signal regulatory protein α1 (SIRPA) were induced by GC/GR in RAW264.7 cells and SIRPA expression was decreased remarkably in RAW-GR(−) cells. Overexpression of SIRPA negatively regulated the proliferation of RAW-GR(−) cells, and inhibition of SIRPA expression by a small from RNA interference attenuated Dex-induced proliferation inhibition in RAW264.7 cells. The proliferation inhibition of GC/GR was also found in mouse peritoneal macrophage, which was associated with the increase in SIRPA induced by GC/GR as well. In addition, elevation of the expression of CDK2, cyclinD1, and cyclinB1, but not phosphorylated ERK1/2 and p38, was found in RAW-GR(−) cells. In conclusion, we provided the novel evidences that GC/GR inhibited the growth of RAW264.7 cells and mouse peritoneal macrophage, and the antiproliferative effect of GC/GR on these cells was at least in part a result from GC/GR-induced SIRPA expression. Up-regulation of CDK2, cyclinD1, and cyclinB1 was also related to the increased proliferation of RAW-GR(−) cells.
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Traganos, Frank. "Cycling without Cyclins." Cell Cycle 3, no. 1 (January 2004): 31–33. http://dx.doi.org/10.4161/cc.3.1.608.
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Holding, Cathy. "Cycling without cyclins." Genome Biology 5 (2004): spotlight—20040824–01. http://dx.doi.org/10.1186/gb-spotlight-20040824-01.
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Wang, Xue, Shuaishuai Huang, Xia Xin, Yu Ren, Guobin Weng, and Ping Wang. "The antitumor activity of umbelliferone in human renal cell carcinoma via regulation of the p110γ catalytic subunit of PI3Kγ." Acta Pharmaceutica 69, no. 1 (March 1, 2019): 111–19. http://dx.doi.org/10.2478/acph-2019-0004.
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Abstract Umbelliferone exhibits extensive pharmacological activity, including anti-immunomodulatory, anti-inflammatory and antigenotoxicity activities. However, its antitumor properties still remain unclear in human renal cell carcinoma (RCC) cells. Our results have revealed that treatment of human RCC cells (786-O, OS-RC-2, and ACHN) with umbelliferone reduced cell proliferation in a concentration-dependent manner and induced dose-dependent apoptotic events. In addition, cell cycle analysis determined that umbelliferone treatment induced cell cycle arrest in the G1 phase in a dose-dependent manner. Furthermore, western blotting analysis showed a dose-dependent decrease in Ki67, MCM2, Bcl-2, CDK2, CyclinE1, CDK4, and CyclinD1 and a dose-dependent increase in Bax in RCC cells cultured with umbelliferone. Similarly, umbelliferone exhibited a dose-dependent reduction of p110γ when using western blotting analyses. Taken together, these results provide an insight into the pharmacology regarding the potential application of umbelliferone, which contributes to cell death by decreasing p110γ protein expression.
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Honoki, Kanya, Hiromasa Fujii, Yasuaki Tohma, Toshifumi Tsujiuchi, Akira Kido, Shinji Tsukamoto, Toshio Mori, and Yasuhito Tanaka. "Comparison of Gene Expression Profiling in Sarcomas and Mesenchymal Stem Cells Identifies Tumorigenic Pathways in Chemically Induced Rat Sarcoma Model." ISRN Oncology 2012 (July 17, 2012): 1–8. http://dx.doi.org/10.5402/2012/909453.
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Mesenchymal stem cells (MSCs) are believed to be the cell of origin for most sarcomas including osteosarcoma and malignant fibrous histiocytoma (MFH/UPS). To identify the signaling pathways involved in sarcoma pathogenesis, we compared gene expression profiles in rat osteosarcoma and MFH cells with those in syngeneic rat MSCs. Analysis of genes that characterize MSCs such as CD44, CD105, CD73, and CD90 showed higher expression in MSCs compared to sarcomas. Pathways involved in focal and cell adhesion, cytokine-cytokine receptors, extracellular matrix receptors, chemokines, and Wnt signaling were down-regulated in both sarcomas. Meanwhile, DNA replication, cell cycle, mismatch repair, Hedgehog signaling, and metabolic pathways were upregulated in both sarcomas. Downregulation of p21Cip1 and higher expression of CDK4-cyclinD1 and CDK2-cyclinE could accelerate cell cycle in sarcomas. The current study indicated that these rat sarcomas could be a good model for their human counterparts and will provide the further insights into the molecular pathways and mechanisms involved in sarcoma pathogenesis.
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Wang, Tianjie, Hongyu Lei, Lihua Zhou, Meiwen Tang, Qing Liu, Feng Long, Qing Li, and Jianming Su. "Effect of Fumonisin B1 on Proliferation and Apoptosis of Intestinal Porcine Epithelial Cells." Toxins 14, no. 7 (July 9, 2022): 471. http://dx.doi.org/10.3390/toxins14070471.
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Fumonisin B1 (FB1), which is a mycotoxin produced by Fusarium moniliforme and Fusarium rotarum, has a number of toxic effects in animals. Moldy feed containing FB1 can damage the intestine. In this study, we used intestinal porcine epithelial cells (IPEC-J2) as an in vitro model to explore the effects of FB1 on cell cycle and apoptosis. The results showed that IPEC-J2 cells treated with 10, 20, and 40 μg/mL FB1 for 48 h experienced different degrees of damage manifested as decreases in cell number and viability, as well as cell shrinkage and floating. In addition, FB1 reduced cell proliferation and the mRNA and protein expression of proliferating cell nuclear antigen (PCNA), cyclin-dependent kinase 2 (CDK2), CDK4, cyclinD1, and cyclinE1. FB1 blocked the cell cycle in the G1 phase. FB1 also induced mitochondrial pathway apoptosis, reduced mitochondrial membrane potential, and promoted mRNA and protein expression of Caspase3, Caspase9, and Bax. The findings suggest that FB1 can induce IPEC-J2 cell damage, block the cell cycle, and promote cell apoptosis.
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Fu, Yuxin, Lun Fang, Qipu Yin, Qi Wu, Wei Sui, Ying Sun, Xindi Zhao, Yadi Wu, and Lu Zhou. "Interfering with pak4 Protein Expression Affects Osteosarcoma Cell Proliferation and Migration." BioMed Research International 2021 (December 30, 2021): 1–10. http://dx.doi.org/10.1155/2021/9977001.
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Purpose. A number of studies have discovered various roles of PAK4 in human tumors, including osteosarcoma. However, the exact role of PAK4 in osteosarcoma and its mechanism have yet to be determined. Therefore, this study focused on interrogating the PAK4 effect on the proliferation and migration ability of osteosarcoma and its underlying mechanisms. Materials and Methods. Western blot and QRT-PCR were utilized to quantify the PAK4 relative protein and mRNA levels. To measure cellular viability and mobility, the MTT and wound-healing assays were preferred. Results. With the adenovirus-mediated overexpression of PAK4, the proliferation and migration of U2-OS and MG-63 osteosarcoma cells were stimulated. Furthermore, a liposome-mediated knockout of PAK4 will inhibit osteosarcoma cells from proliferating. In terms of mechanism, we observed the positive correlation of PAK4 expression with expression of P21, CyclinD1, CyclinE1, CDK2, and CDK6, which drives G0/G1 to the G2/M phase transition. PAK4 can also activate Erk expression in OS cells and induce EMT. Conclusion. Interfering with PAK4 protein expression has been shown to affect osteosarcoma proliferation and migration.
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Wang, Jing, Shuangmei Liu, Yijun Nie, Bing Wu, Qin Wu, Miaomiao Song, Min Tang, et al. "Activation of P2X7 receptors decreases the proliferation of murine luteal cells." Reproduction, Fertility and Development 27, no. 8 (2015): 1262. http://dx.doi.org/10.1071/rd14381.
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Extracellular ATP regulates cellular function in an autocrine or paracrine manner through activating purinergic signalling. Studies have shown that purinergic receptors were expressed in mammalian ovaries and they have been proposed as an intra-ovarian regulatory mechanism. P2X7 was expressed in porcine ovarian theca cells and murine and human ovarian surface epithelium and is involved in ATP-induced apoptotic cell death. However, the role of P2X7 in corpus luteum is still unclear. The aim of this study was to investigate the role of ATP signalling in murine luteal cells and the possible mechanism(s) involved. We found that P2X7 was highly expressed in murine small luteal cells. The agonists of P2X7, ATP and BzATP, inhibited the proliferation of luteal cells. P2X7 antagonist BBG reversed the inhibition induced by ATP and BzATP. Further studies showed that ATP and BzATP inhibited the expression of cell cycle regulators cyclinD2 and cyclinE2. ATP and BzATP also inhibited the p38–mitogen-activated protein kinase (MAPK) signalling pathway. These results reveal that P2X7 receptor activation is involved in corpus luteum formation and function.
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Yakufu, Mirensha, Renaguli Hailiwu, Yuanyuan Cong, Ayijiang Habaike, Xiaomei Wang, and Palida Abulizi. "Antitumor activity of flavonoids from Alpinia officinarum hance on gastric cancer." European Journal of Inflammation 19 (January 2021): 205873922110511. http://dx.doi.org/10.1177/20587392211051119.
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Introduction: To investigate antitumor activity and mechanism of flavonoids from Alpinia officinarum Hance against gastric cancer. Methods: Transplanted mouse fore-stomach carcinoma (MFC) tumor mice were divided into six groups: control group, model group, low dose (20 mg/kg), middle dose (40 mg/kg), and high dose (80 mg/kg) groups of TFAO and 5-Fu group. Mice were treated with TFAO or 5-Fu for 14 days, except those of control and model group. Tumor inhibitory rate, spleen, and thymus index were calculated. Contents of proliferating cell nuclear antigen, MMP-9, vascular endothelial growth factor, IL-1β, IL-6, and IL-17 in serum were detected. Effect of galangin on BGC-823 cell growth was detected. Cell apoptosis and cell cycle distribution were measured. Enzyme activity of Caspase-3, Caspase-8, and Caspase-9 was detected. Western blot was used to detect STAT3, Bcl-2, Bax, Caspase-3, Caspase-8, Caspase-9, CyclinB1, and CyclinD1 protein expression in BGC-823 cell. Results: Compared with model group, tumor weight of mice decreased significantly ( p < .01) in 5-Fu group, low dose, middle dose, and high dose group of TFAO; thymus index of mice decreased significantly ( p < .05) in 5-Fu group; and spleen index decreased significantly ( p < .05) in low dose and middle dose groups of TFAO. Compared with model group, levels of PCNA, MMP-9, IL-1β, and IL-6 in serum of mice decreased obviously ( p < .01) in all administration groups; levels of VEGF in serum of mice decreased obviously ( p < .01) in low dose and high dose group of TFAO and 5-Fu group; and levels of IL-17 in serum of mice decreased significantly ( p < .01) in low-dose and middle-dose groups of TFAO and 5-Fu group. Galangin could inhibit BGC-823 cell growth; accelerate apoptosis; block cell cycle; increase cell Caspase-3, Caspase-8, and Caspase-9 enzyme activity; upregulate expression of Caspase-3, Caspase-8, Caspase-9, and Bax; and downregulate expression of STAT3, CyclinB1, CyclinD1, and Bcl-2 protein. Conclusion: Flavonoids from A. officinarum showed antitumor activity in gastric cancer. Mechanisms may be associated with inhibition of tumor angiogenesis, tumor cell proliferation, and cancer-associated inflammation.
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Peng, Xiyang, Yao Wen, Lagabaiyila Zha, Jian Zhuang, Li Lin, Xu Li, Yu Chen, et al. "TRIM45 Suppresses the Development of Non-small Cell Lung Cancer." Current Molecular Medicine 20, no. 4 (March 20, 2020): 299–306. http://dx.doi.org/10.2174/1566524019666191017143833.
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Background: Previously, we first identified the human tripartite motifcontaining protein 45 (TRIM45) acts as a novel transcriptional repressor in mitogenactivated protein kinase (MAPK) signaling pathway. After that, the inhibitory role of TRIM45 in the development of tumor was gradually unveiled. However, the function of TRIM45 in the tumorigenesis of lung cancer has not been characterized. Methods and Results: In this study, we found that TRIM45 was up-regulated in earlystage human non-small-cell lung cancer (NSCLC) tissues. Overexpression of TRIM45 in lung cancer cells induces G1 arrest and promotes apoptosis, which accompanied by upregulated expression of RB, p16, p53, p27Kip1, and Caspase3 and down-regulated expression of CyclinE1 and CyclinE2. Further detection of the expression of the molecules in the MAPK signaling pathway revealed that overexpression of TRIM45 in lung cancer cells promotes phosphorylated p38 (p-p38) activation and inhibits phosphorylated ERK (p-ERK) activation. In accordance with this, p-p38 is increased while p-ERK is decreased in lung cancer tissues. Conclusion: These findings indicate that TRIM45 plays an inhibitory role in the tumorigenesis of lung cancer. High-level expression of TRIM45 in lung cancer tissue may promote cell apoptosis by activating p38 signal and inhibit proliferation by down-regulating p-ERK, which provides a new clue for understanding the tumorigenesis of lung cancer.
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Hur, Dae Young, Ga Bin Park, Hyunkeun Song, Yeong-Seok Kim, Minjung Sung, Hyun-Kyung Lee, and Wang Jae Lee. "Cell cycle arrest and apoptosis induced by engagement of B7-H4 on EBV-positive B lymphoma cells (40.21)." Journal of Immunology 182, no. 1_Supplement (April 1, 2009): 40.21. http://dx.doi.org/10.4049/jimmunol.182.supp.40.21.
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Abstract B7-H4 is a recently discovered B7 family member that has inhibitory effect on T cell immunity. However, the signaling mechanism of the B7-H4-expressing cells remains unclear. Previous work has shown that B7-H4 expression was enhanced on B cells by infection of Epstein-Barr virus (EBV), and engagement of induced B7-H4 exerted cell death of EBV-transformed B cells. Here we found that B7-H4 was constitutively expressed on EBV-positive Burkitt¡ s lymphoma cells and that engagement of B7-H4 significantly reduced cell viability of Raji cell. Engagement of B7-H4 resulted cell cycle arrest at G0-G1 phase in a dose- and time-dependent manner. To clarify the mechanism of B7-H4 triggering induced cell cycle arrest, cell cycle regulatory factor was examined by RT-PCR and immunoblotting. B7-H4 triggering down-regulated CDK4/6 and up-regulated p21 expression at both protein and RNA level. Furthermore, CDK2 and cyclineE/D expression was down-regulated by B7-H4 triggering. Additionally, the down-regulation of phospho-AKT and phospho-cyclinE was clearly detected in B7-H4 triggering Raji cells, but the phosphorylation of p53 was constitutively maintained. These results represent that B7-H4-mediated signaling on EBV-positive B cells modulates cell cycle through down-regulation of AKT pathway. We conclude that B7-H4 may have the potency for use in EBV-associated cancer therapy.
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Nakamura-Ishizu, Ayako, Yuji Okuno, Yoshiki Omatsu, Keisuke Okabe, Junko Morimoto, Toshimitsu Uede, Takashi Nagasawa, Toshio Suda, and Yoshiaki Kubota. "Extracellular matrix protein tenascin-C is required in the bone marrow microenvironment primed for hematopoietic regeneration." Blood 119, no. 23 (June 7, 2012): 5429–37. http://dx.doi.org/10.1182/blood-2011-11-393645.
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Abstract The BM microenvironment is required for the maintenance, proliferation, and mobilization of hematopoietic stem and progenitor cells (HSPCs), both during steady-state conditions and hematopoietic recovery after myeloablation. The ECM meshwork has long been recognized as a major anatomical component of the BM microenvironment; however, the molecular signatures and functions of the ECM to support HSPCs are poorly understood. Of the many ECM proteins, the expression of tenascin-C (TN-C) was found to be dramatically up-regulated during hematopoietic recovery after myeloablation. The TN-C gene was predominantly expressed in stromal cells and endothelial cells, known as BM niche cells, supporting the function of HSPCs. Mice lacking TN-C (TN-C−/−) mice showed normal steady-state hematopoiesis; however, they failed to reconstitute hematopoiesis after BM ablation and showed high lethality. The capacity to support transplanted wild-type hematopoietic cells to regenerate hematopoiesis was reduced in TN-C−/− recipient mice. In vitro culture on a TN-C substratum promoted the proliferation of HSPCs in an integrin α9–dependent manner and up-regulated the expression of the cyclins (cyclinD1 and cyclinE1) and down-regulated the expression of the cyclin-dependent kinase inhibitors (p57Kip2, p21Cip1, p16Ink4a). These results identify TN-C as a critical component of the BM microenvironment that is required for hematopoietic regeneration.
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Liu, Aihua, Zhongfu Zuo, Linlin Liu, and Lihua Liu. "Down-regulation of NTSR3 inhibits cell growth and metastasis, as well as the PI3K–AKT and MAPK signaling pathways in colorectal cancer." Biochemistry and Cell Biology 98, no. 5 (October 2020): 548–55. http://dx.doi.org/10.1139/bcb-2019-0351.
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Colorectal cancer is a common malignancy. NTS receptor 3 (NTSR3) is known to play an important role in several cancers. This study examined the effects of NTSR3 on cell growth and metastasis in colorectal cancer. Western blot analysis, real-time PCR, immunofluorescence staining, MTT, cell cycle assay, cell apoptosis assay, Hoechst staining, caspase-3 and caspase-9 activity assays, cell adhesion assay, wound healing assay, and a Transwell assay were used in this study. We found that NTSR3 was expressed at relatively high levels in the colorectal cancer cell lines SW620 and SW480. NTSR3 knockdown suppressed cell growth and promoted cell apoptosis. Meanwhile, the protein expression levels of cyclinD1, cyclinE1, CDK4, and p-RB were reduced, and the levels of p-P27, P15, P21, cleaved caspase-3, and cleaved caspase-9 protein were increased. Cell invasiveness and cell migration were reduced with knockdown of NTSR3. In addition, our rescue experiments demonstrated that overexpression of the siRNA-resistant alleles of NTSR3 abrogated the NTSR3-siRNA-mediated effects on cell function. Further, down-regulation of NTSR3 inactivated the PI3K–AKT and MAPK signaling pathways. Collectively, these data demonstrate that knockdown of NTSR3 inhibits cell growth and metastasis, as well as the PI3K–AKT and MAPK signaling pathways in colorectal cancer. Thus, our results indicate that NTSR3 is a potential therapeutic target for treating colorectal cancer.
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Meng, Chunqin, Yuhao Teng, and Xiaodong Jiang. "Raddeanin A Induces Apoptosis and Cycle Arrest in Human HCT116 Cells through PI3K/AKT Pathway Regulation In Vitro and In Vivo." Evidence-Based Complementary and Alternative Medicine 2019 (May 26, 2019): 1–11. http://dx.doi.org/10.1155/2019/7457105.
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This study aimed to investigate the in vitro and in vivo effects of Raddeanin A on apoptosis and the cell cycle in the human colorectal cell line, HCT116, and to explore the possible underlying mechanisms of action. We found the growth inhibition rate gradually increased as the drug concentration increased via the 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, which indicated that Raddeanin A significantly inhibited the growth of HCT116 cells. Flow cytometry (FCM) showed that Raddeanin A concentration-dependently induced apoptosis in HCT116 cells. In addition, the percentage of cells in the G0/G1phase was noticeably increased, which indicated that Raddeanin A blocked cell cycle progression in HCT116 cells and caused arrest in the G0/G1phase. Moreover, the expression of proteins involved in the PI3K/AKT signaling pathway (e.g., p-PI3K and p-AKT) was decreased. The results showed that in vivo revealed that Raddeanin A significantly inhibited tumor growth in an HCT116-xenografted mouse model; apoptotic cells were also detected in the tumor tissue. The expression of the tissue proteins cyclinD1, cyclinE, p-PI3K, and p-AKT was decreased. The above results show that the Raddeanin A exerted a strong antitumor effect in the human colorectal cell line HCT116 both in vitro and in vivo. This effect may be caused by the induction of apoptosis and cycle arrest achieved through PI3K/AKT signaling pathway regulation.
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Liang, Quan, Qingjuan Yao, and GuoYing Hu. "CyclinD1 is a new target gene of tumor suppressor miR-520e in breast cancer." Open Medicine 14, no. 1 (December 4, 2019): 913–19. http://dx.doi.org/10.1515/med-2019-0108.
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AbstractObjectiveTo investigate the involvement of miR-520e in the modulation of cancer-promoting cyclinD1 in breast cancer.MethodsA reverse transcription-polymerase chain reaction (RT-PCR) was applied to test the regulation of miR-520e on cyclinD1. The binding of miR-520e to 3’-untranslated region (3’UTR) of cyclinD1 mRNA was predicted by an online bioinformatics website. The effect of miR-520e on the luciferase reporters with binding sites of miR-520e and 3’UTR of cyclinD1 mRNA was revealed using a luciferase reporter gene assay. The correlation between miR-520e and cyclinD1 in clinical breast cancer samples was detected through quantitative real-time PCR.ResultsThe expression of cyclinD1 was gradually reduced as the dose of miR-520e increased. Anti-miR-520e obviously induced cyclinD1 in breast cancer cells. After anti-miR-520e was introduced into the cells, the inhibition of cyclinD1 expression mediated by miR-520e was reversed. The binding of miR-520e with cyclinD1 was revealed via bioinformatics. Under the treatment of dose-increasing miR-520e or anti-miR-520e, the luciferase activities of cyclinD1 3’UTR vector were lower or higher by degrees. However, the activity of the mutant vector was not affected at all. Finally, in clinical breast cancer tissues the negative correlation of miR-520e with cyclinD1 was revealed.ConclusionIn conclusion, cyclinD1 is a new target of miR-520e in breast cancer.
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Rattanaburee, Thidarath, Chompunud Chompunud Na Ayudhya, Tienthong Thongpanchang, Varomyalin Tipmanee, and Potchanapond Graidist. "Trans-(±)-TTPG-B Attenuates Cell Cycle Progression and Inhibits Cell Proliferation on Cholangiocarcinoma Cells." Molecules 28, no. 21 (October 30, 2023): 7342. http://dx.doi.org/10.3390/molecules28217342.
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This research aimed to determine the target protein and molecular mechanism of trans-(±)-kusunokinin ((±)-KU) derivatives (trans-(±)-ARC and trans-(±)-TTPG-B). Molecular docking was used to predict potential synthesized (±)-KU targets among 22 proteins. The (±)-TTPG-B bound HSP90α better than EC44, native (±)-KU and (-)-KU, and (±)-KU and (−)-ARC. In contrast, (−)-ARC bound PI3K more strongly than any other test compound. CSF1R and AKR1B1 were not supposed to be the target of (±)-TTPG-B and (±)-ARC, unlike native (±)-KU. The (±)-TTPG-B bound Tyr139 and Trp162 of HSP90α. Moreover, (−)-ARC bound PI3K via hydrogen bonds and π-π stacking at distinct amino acids, which was different from the other tested compounds. Using half of the IC50 concentration, (±)-TTPG-B, (±)-KU and (±)-ARC enhanced cell cycle arrest at the G0/G1 phase after 12 h and 24 h on KKU-M213 (CCA) cells. The (±)-TTPG-B showed a stronger inhibitory effect than (±)-ARC and (±)-KU on HSP90α, PI3K, HSP90β, c-Myc, AKT, MEK1, CyclinB1, CyclinD1, and CDK1 for 24 and 48 h after treatment with the same concentration (0.015 µM). Thus, trans-(±)-TTPG-B, a newly synthesized compound, has pharmacological potential for development as a target therapy for CCA treatment.
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Choi, Yae Rim, Hyun-Jin Na, Jaekwang Lee, Young-Suk Kim, and Min Jung Kim. "Isoeugenol Inhibits Adipogenesis in 3T3-L1 Preadipocytes with Impaired Mitotic Clonal Expansion." Nutrients 16, no. 9 (April 24, 2024): 1262. http://dx.doi.org/10.3390/nu16091262.
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Isoeugenol (IEG), a natural component of clove oil, possesses antioxidant, anti-inflammatory, and antibacterial properties. However, the effects of IEG on adipogenesis have not yet been elucidated. Here, we showed that IEG blocks adipogenesis in 3T3-L1 cells at an early stage. IEG inhibits lipid accumulation in adipocytes in a concentration-dependent manner and reduces the expression of mature adipocyte-related factors including PPARγ, C/EBPα, and FABP4. IEG treatment at different stages of adipogenesis showed that IEG inhibited adipocyte differentiation by suppressing the early stage, as confirmed by lipid accumulation and adipocyte-related biomarkers. The early stage stimulates growth-arrested preadipocytes to enter mitotic clonal expansion (MCE) and initiates their differentiation into adipocytes by regulating cell cycle-related factors. IEG arrested 3T3-L1 preadipocytes in the G0/G1 phase of the cell cycle and attenuated cell cycle-related factors including cyclinD1, CDK6, CDK2, and cyclinB1 during the MCE stage. Furthermore, IEG suppresses reactive oxygen species (ROS) production during MCE and inhibits ROS-related antioxidant enzymes, including superoxide dismutase1 (SOD1) and catalase. The expression of cell proliferation-related biomarkers, including pAKT and pERK1/2, was attenuated by the IEG treatment of 3T3-L1 preadipocytes. These findings suggest that it is a potential therapeutic agent for the treatment of obesity.
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Pan, Weizhe, Shengnan Yu, Jin Jia, Junyang Hu, Liang Jie, Panhong Zhang, Qian Wang, Xiaoyan Yan, and Yulan Qiu. "Deregulation of the cell cycle and related microRNA expression induced by vinyl chloride monomer in the hepatocytes of rats." Toxicology and Industrial Health 37, no. 6 (May 11, 2021): 365–76. http://dx.doi.org/10.1177/07482337211015591.
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Vinyl chloride (VC) is a confirmed human carcinogen associated with hepatocellular carcinoma and angiosarcoma. However, the role of microRNAs (miRNAs) in liver cell cycle changes under VC exposure remains unclear, which prevents research on the mechanism of VC-induced carcinogenesis. In this study, male rats were injected intraperitoneally with VC (0, 5, 25, and 125 mg/kg body weight) for 6, 8, and 12 weeks. Cell cycle analysis of liver cells, miRNA-222, miRNA-199a, miRNA-195, and miRNA-125b expression in the liver and serum, and target protein expression were performed at different time points. The results showed a higher percentage of hepatocytes in the G1/G0 and S phases at the end of 6 and 12 weeks of VC exposure, respectively. MiRNA-222 expression decreased initially and then increased, whereas miRNA-199a, miRNA-195, and miRNA-125b expression increased initially and then decreased, which corresponded with changes in cell cycle distribution and related target proteins expression (p27, cyclinA, cyclinD1, and CDK6). The corresponding expression levels of miRNAs in serum did not change. Dynamic changes in miR-222, miR-199a, miR-195, and miR-125b induced by VC can lead to cell cycle deregulation by affecting cell cycle-related proteins, and these miRNAs can serve as early biomarkers for malignant transformation caused by VC.
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Li, Chenyang, Yue Wang, Hao Wang, Bowen Wang, Yunxia Wang, Nan Li, Yanli Qin, and Yesheng Wang. "miR-486 Promotes the Invasion and Cell Cycle Progression of Ovarian Cancer Cells by Targeting CADM1." Analytical Cellular Pathology 2021 (August 5, 2021): 1–13. http://dx.doi.org/10.1155/2021/7407086.
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Objective. To explore the role and possible underlying mechanism of miR-486 in ovarian cancer (OC) cells. Methods. The expression of miR-486 and CADM1 was detected by qRT-PCR in OC tissues and adjacent nontumor tissues and OC cell lines. The dual-luciferase reporter gene system was used to determine the targeting relationship between miR-486 and CADM1. CCK-8, colony formation assay, Transwell, and flow cytometry were performed to detect cell proliferation, cell invasion, cell cycle progression, and the apoptotic cell death, respectively. Western blot was carried out to detect the expression of CADM1 protein and the proteins associated with cell cycle progression. Results. miR-486 was significantly upregulated in OC tissues and cells, while CADM1 expression was significantly downregulated. Dual-luciferase reporter assays further confirmed that CADM1 was a target gene of miR-486. Interference with miR-486 could inhibit the proliferation and invasion and promoted the apoptosis of SKOV3 cells. Knocking down both miR-486 and CADM1 significantly increased the SKOV3 cell proliferation, invasion, and the number of cells transitioning from the G0/G1 phase into the S phase of cell cycle and reduced the cellular apoptosis. Western blot analysis revealed that the expression of cell cycle progression-related proteins (CyclinD1, CyclinE, and CDK6) was significantly reduced, and the p21 expression was increased when interfering with both miR-486 and CADM1 expression. Conclusion. Our results suggested that miR-486 could act as a tumor promoter by targeting CADM1 and be a potential therapeutic target for the treatment of OC.
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Savvidou, Ioanna, Tiffany Khong, Sophie Whish, Irena Carmichael, Tara Sepehrizadeh, Sridurga Mithraprabhu, Stephen K. Horrigan, Michael de Veer, and Andrew Spencer. "Combination of Histone Deacetylase Inhibitor Panobinostat (LBH589) with β-Catenin Inhibitor Tegavivint (BC2059) Exerts Significant Anti-Myeloma Activity Both In Vitro and In Vivo." Cancers 14, no. 3 (February 8, 2022): 840. http://dx.doi.org/10.3390/cancers14030840.
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Over the last three decades changes in the treatment paradigm for newly diagnosed multiple myeloma (MM) have led to a significant increase in overall survival. Despite this, the majority of patients relapse after one or more lines of treatment while acquiring resistance to available therapies. Panobinostat, a pan-histone deacetylase inhibitor, was approved by the FDA in 2015 for patients with relapsed MM but how to incorporate panobinostat most effectively into everyday practice remains unclear. Dysregulation of the Wnt canonical pathway, and its key mediator β-catenin, has been shown to be important for the evolution of MM and the acquisition of drug resistance, making it a potentially attractive therapeutic target. Despite concerns regarding the safety of Wnt pathway inhibitors, we have recently shown that the β-catenin inhibitor Tegavivint is deliverable and effective in in vivo models of MM. In this study we show that the combination of low concentrations of panobinostat and Tegavivint have significant in vitro and in vivo anti-MM effects including in the context of proteasome inhibitor resistance, by targeting both aerobic glycolysis and mitochondrial respiration and the down-regulation of down-stream β-catenin targets including myc, cyclinD1, and cyclinD2. The significant anti-MM effect of this novel combination warrants further evaluation for the treatment of MM patients with relapsed and/or refractory MM.
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Wang, Zhi, Mengkai Hu, Ming Fang, Qiang Wang, Ruiqi Lu, Hengwei Zhang, Meijuan Xu, Xian Zhang, and Zhiming Rao. "Heterologous Expression of Thermotolerant α-Glucosidase in Bacillus subtilis 168 and Improving Its Thermal Stability by Constructing Cyclized Proteins." Fermentation 8, no. 10 (September 29, 2022): 498. http://dx.doi.org/10.3390/fermentation8100498.
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α-glucosidase is an essential enzyme for the production of isomaltooligosaccharides (IMOs). Allowing α-glucosidase to operate at higher temperatures (above 60 °C) has many advantages, including reducing the viscosity of the reaction solution, enhancing the catalytic reaction rate, and achieving continuous production of IMOs. In the present study, the thermal stability of α-glucosidase was significantly improved by constructing cyclized proteins. We screened a thermotolerant α-glucosidase (AGL) with high transglycosylation activity from Thermoanaerobacter ethanolicus JW200 and heterologously expressed it in Bacillus subtilis 168. After forming the cyclized α-glucosidase by different isopeptide bonds (SpyTag/SpyCatcher, SnoopTag/SnoopCatcher, SdyTag/SdyCatcher, RIAD/RIDD), we determined the enzymatic properties of cyclized AGL. The optimal temperature of all cyclized AGL was increased by 5 °C, and their thermal stability was generally improved, with SpyTag-AGL-SpyCatcher having a 1.74-fold increase compared to the wild-type. The results of molecular dynamics simulations showed that the RMSF values of cyclized AGL decreased, indicating that the rigidity of the cyclized protein increased. This study provides an efficient method for improving the thermal stability of α-glucosidase.
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Yang, Hua, Pengcheng Ma, Yuping Cao, Mengli Zhang, Lingjun Li, Jun Wei, Lei Tao, and Kun Qian. "ECPIRM, a Potential Therapeutic Agent for Cutaneous T-Cell Lymphoma, Inhibits Cell Proliferation and Promotes Apoptosis via a JAK/STAT Pathway." Anti-Cancer Agents in Medicinal Chemistry 18, no. 3 (June 4, 2018): 401–11. http://dx.doi.org/10.2174/1871520617666170327115657.
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Background: Retinoids are important agents for the treatment of cutaneous T-cell lymphomas (CTCL). But side effects and drug resistance caused by activation of RAR/RXR limited their clinical application. Therefore, it is urgent to develop new agents to fight against CTCL. ECPIRM, a 13-cis retinoic acid derivative, was reported that it inhibited proliferation and induced apoptosis of SCL-1 cells. Objective: The aim of this study was to evaluate the biological activities and mechanisms of ECPIEM. Methods: The effect of ECPIRM on cell proliferation was determined by MTT assay and Trypan blue exclusion assay while FACS analysis was used to detect changes in cell cycle and apoptosis in HUT78 cells. The influence of ECPIRM on RAR/RXR and JAK/STAT signaling was evaluated by western blot analysis. Results: ECPIRM, better than other agents (all-trans retinoic acid,13-cis-retinoic acid or bexarotene), inhibited proliferation and induced apoptosis significantly in HUT78 cells, but with little cytotoxicity on normal lymphocytes. Then ECPIRM induced G0/G1 phase arrest by decreasing the expression of cyclinD1, cyclinE, CDK2 and CDK4 while increasing p21. Furthermore, the unaffected expression of RAR and RXR members suggested that ECPIRM acted independently of RAR/RXR pathway in HUT78 cells. But decreased phosphorylation of JAK1, STAT3, STAT5 and downregulated Bcl-xL, Cyclin D1 and c-Myc indicated that ECPIRM inhibited the activation of JAK/STAT signaling. Conclusion: ECPIRM inhibited proliferation, induced apoptosis and G0/G1 phase arrest in HUT78 cells through inhibiting JAK/STAT pathway but not RAR/RXR pathway, which presented ECPIRM as a promising candidate for the treatment of CTCL patients.
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Smith, Cecilia U., Sybil D’Costa, Enrique M. Rabellino, Vincent Shankey, and Julie Wilkinson. "CyclinA2 as a Proliferation Marker for Peripheral Blood T Cell Subsets Measured by Flow Cytometry." Blood 106, no. 11 (November 16, 2005): 3324. http://dx.doi.org/10.1182/blood.v106.11.3324.3324.
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Abstract Proliferation is regarded as a sensitive parameter for assessing immune response to infectious agents, autoimmune conditions, and organ engraftment in transplantation. Proliferation of peripheral blood mononuclear (PBMC) cells has been measured by a number of flow cytometric methods including propidium iodide (PI), incorporation of Bromo-deoxy-uridine (BrdUr), and dilution of Carboxy-fluorescein diacetate, succinimidyl ester (CFSE) intensity. Standardization of these methods however, has been hampered by their technical complexity. The restricted expression of CyclinA2 protein in the cytoplasm during the S and G2 cell cycle phases has provided the basis for a simplified intracellular flow-based proliferation assay. In these studies, ex vivo stimulated human PBMC were tested for the validation of CyclinA2 as a proliferation marker for T cell subsets. Freshly isolated or cryopreserved PBMCs were incubated in vitro with SEB/CD28 for periods up to 72 hours and processed using different methodologies for lymphocyte cell cycle measurement. These included BrdUr /7AAD, PI/CyclinA2; cylinA2 with additional T cell phenotyping markers and a combined CyclinA2 /BrdUr proliferation method. Results for each cell subset were scored for the percentage of positive proliferating cells by each methodology. PBMC co-stained for CyclinA2 and DNA content by PI demonstrated that all cells expressing Cyclin A2 corresponded to cells at S or G2 phase. Furthermore, the time course assays combining BrdUr labeling with CvclinA2 confirmed that CyclinA2 expression corresponded selectively to cells incorporating BrdUr. When PMBC were surface phenotyped for CD3 and CD4/CD8, reproducible populations of CD4 and CD8 T cell subsets incorporating BrdUr were measured for expression of Cyclin A2. In our assay model 11 to 15 % positively stained for Cyclin A2 corresponded to approximately 10% and 5% of CD3/8 and CD3/4 CyclinA2 cells, respectively. The percentage of total BrdUr and total CyclinA2 positive cells that were detected in the dual-labeled specimens corresponded to the percentage detected by each individual method. In conclusion, measurement of in vitro lymphocytes proliferation using expression of CyclinA2 protein expression is highly correlated with BrdUr uptake demonstrating that CyclinA2 is an accurate marker of cell proliferation. Preparation of cells for measuring Cyclin A2 takes only 60 minutes as compared with a total 12 to 16 hours for BrdUr pulsing and staining time. The simple CyclinA2 preparation method described here makes it a practical, fast, and reliable proliferation flow assay that can be easily standardized for enumeration of proliferating lymphocyte subsets.
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Bouftas, Nora, and Katja Wassmann. "Cycling through mammalian meiosis: B-type cyclins in oocytes." Cell Cycle 18, no. 14 (June 23, 2019): 1537–48. http://dx.doi.org/10.1080/15384101.2019.1632139.
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Taki, Keigo, Hiroshi Takagi, Tomonori Hirose, Runan Sun, Hiroshi Yaginuma, Akira Mizoguchi, Tomoko Kobayashi, et al. "Dietary sodium chloride attenuates increased β-cell mass to cause glucose intolerance in mice under a high-fat diet." PLOS ONE 16, no. 3 (March 17, 2021): e0248065. http://dx.doi.org/10.1371/journal.pone.0248065.
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Excessive sodium salt (NaCl) or fat intake is associated with a variety of increased health risks. However, whether excessive NaCl intake accompanied by a high-fat diet (HFD) affects glucose metabolism has not been elucidated. In this study, C57BL/6J male mice were fed a normal chow diet (NCD), a NCD plus high-NaCl diet (NCD plus NaCl), a HFD, or a HFD plus high-NaCl diet (HFD plus NaCl) for 30 weeks. No significant differences in body weight gain, insulin sensitivity, and glucose tolerance were observed between NCD-fed and NCD plus NaCl-fed mice. In contrast, body and liver weights were decreased, but the weight of epididymal white adipose tissue was increased in HFD plus NaCl-fed compared to HFD-fed mice. HFD plus NaCl-fed mice had lower plasma glucose levels in an insulin tolerance test, and showed higher plasma glucose and lower plasma insulin levels in an intraperitoneal glucose tolerance test compared to HFD-fed mice. The β-cell area and number of islets were decreased in HFD plus NaCl-fed compared to HFD-fed mice. Increased Ki67-positive β-cells, and increased expression levels of Ki67, CyclinB1, and CyclinD1 mRNA in islets were observed in HFD-fed but not HFD plus NaCl-fed mice when compared to NCD-fed mice. Our data suggest that excessive NaCl intake accompanied by a HFD exacerbates glucose intolerance, with impairment in insulin secretion caused by the attenuation of expansion of β-cell mass in the pancreas.
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Zeng, Zhirui, Xiao-Lei Liu, Kristen R. Farley, Jeremy H. Wei, William W. Metcalf, Roger E. Summons, and Paula V. Welander. "GDGT cyclization proteins identify the dominant archaeal sources of tetraether lipids in the ocean." Proceedings of the National Academy of Sciences 116, no. 45 (October 7, 2019): 22505–11. http://dx.doi.org/10.1073/pnas.1909306116.
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Glycerol dibiphytanyl glycerol tetraethers (GDGTs) are distinctive archaeal membrane-spanning lipids with up to eight cyclopentane rings and/or one cyclohexane ring. The number of rings added to the GDGT core structure can vary as a function of environmental conditions, such as changes in growth temperature. This physiological response enables cyclic GDGTs preserved in sediments to be employed as proxies for reconstructing past global and regional temperatures and to provide fundamental insights into ancient climate variability. Yet, confidence in GDGT-based paleotemperature proxies is hindered by uncertainty concerning the archaeal communities contributing to GDGT pools in modern environments and ambiguity in the environmental and physiological factors that affect GDGT cyclization in extant archaea. To properly constrain these uncertainties, a comprehensive understanding of GDGT biosynthesis is required. Here, we identify 2 GDGT ring synthases, GrsA and GrsB, essential for GDGT ring formation in Sulfolobus acidocaldarius. Both proteins are radical S-adenosylmethionine proteins, indicating that GDGT cyclization occurs through a free radical mechanism. In addition, we demonstrate that GrsA introduces rings specifically at the C-7 position of the core GDGT lipid, while GrsB cyclizes at the C-3 position, suggesting that cyclization patterns are differentially controlled by 2 separate enzymes and potentially influenced by distinct environmental factors. Finally, phylogenetic analyses of the Grs proteins reveal that marine Thaumarchaeota, and not Euryarchaeota, are the dominant source of cyclized GDGTs in open ocean settings, addressing a major source of uncertainty in GDGT-based paleotemperature proxy applications.
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Li, Suting, Danhua Lu, Jianming Tang, Jie Min, Ming Hu, Yang Li, Yaodan Liu, Linlin Wang, Cheng Liu, and Li Hong. "Electrical Stimulation Activates Fibroblasts through the Elevation of Intracellular Free Ca2+: Potential Mechanism of Pelvic Electrical Stimulation Therapy." BioMed Research International 2019 (April 21, 2019): 1–10. http://dx.doi.org/10.1155/2019/7387803.
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Ca2+ is an important ion in response to electrical stimulation (ES) and acts as second messenger in the regulation of various physiological processes. Pelvic floor electrical stimulation (PES) is a low-voltage clinical application, available for urinary incontinence (UI) treatment. Fibroblasts, as the main cellular component of vaginal wall and pelvic ligament, play an important role in the maintenance of pelvic health. We studied the effect of ES on fibroblasts in this study. ES was conducted with electrotaxis chambers on L929 fibroblast and the ES parameter was 100 mV/mm×2h. The results showed that ES increased intracellular Ca2+ concentration, promoted the expression of PCNA, CyclinB1, and CyclinD1, and increased the proportion of cells in S and G2 phages. After ES, fibroblasts get activated and proliferated. Besides, BAPTA-AM, a membrane permeated chelator for intracellular free Ca2+, partially inhibited the effect of ES on fibroblasts activation and proliferation promotion. Furthermore, we elucidated that Ca2+, as a second messenger and upstream signal for Smads and Akt signaling, regulated ES-induced nuclear translocation of smad2/3, phosphorylation of smad2/3, Akt, and GSK3β. Finally, we validated the effect of ES on PES mouse model. The results indicated that PES promoted the activation and proliferation of fibroblasts in vivo. In conclusion, we verify that ES can elevate the concentration of intracellular Ca2+ and activate its downstream signaling and then promote the activation of fibroblasts, which may be one of the mechanisms of PES therapy.
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Menjanahary, Jean Michel, and Raimundas Vidunas. "Dupin Cyclides Passing through a Fixed Circle." Mathematics 12, no. 10 (May 11, 2024): 1505. http://dx.doi.org/10.3390/math12101505.
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Dupin cyclides are classical algebraic surfaces of low degree. Recently, they have gained popularity in computer-aided geometric design (CAGD) and architecture owing to the fact that they contain many circles. We derive algebraic conditions that fully characterize the Dupin cyclides passing through a fixed circle. The results are applied to the basic problem in CAGD of the blending of Dupin cyclides along circles.
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Ohashi, Y., M. Kawai, and T. Kaito. "Inelastic Behavior of Type 316 Stainless Steel Under Multiaxial Nonproportional Cyclic Stressings at Elevated Temperature." Journal of Engineering Materials and Technology 107, no. 2 (April 1, 1985): 101–9. http://dx.doi.org/10.1115/1.3225781.
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The stress-range and path-shape dependencies of multiaxial nonproportional cyclic hardening were studied for annealed type 316 stainless steel at 600°C by means of stress controlled tests. Cyclic experiments along circular stress paths with constant effective stresses in the axial-torsional stress plane were first performed. The significant cyclic hardening and its stress-range dependency observed for the circular stress cyclings were quantitatively shown in reference to the cyclic stress-strain curves resulted from uniaxial stress cyclings. Then, to discuss the effect of path-shape, the cyclic tests along square stress paths inscribed by the above circular paths, as well as the tests where uniaxial cyclings and torsional ones were alternated, were also carried out. As a result of these tests, the cyclic hardenings for square paths were found to be almost equivalent to those for their circumscribed circular paths. The other type of stress cyclings caused almost the same amount of cyclic hardenings as those for the circular cyclings of the identical stress-ranges.
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Major, Daniel, Lara Flanzbaum, Leah Lussier, Carly Davies, Kristian Mark P. Caldo, and Jeella Z. Acedo. "Transporter Protein-Guided Genome Mining for Head-to-Tail Cyclized Bacteriocins." Molecules 26, no. 23 (November 28, 2021): 7218. http://dx.doi.org/10.3390/molecules26237218.
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Head-to-tail cyclized bacteriocins are ribosomally synthesized antimicrobial peptides that are defined by peptide backbone cyclization involving the N- and C- terminal amino acids. Their cyclic nature and overall three-dimensional fold confer superior stability against extreme pH and temperature conditions, and protease degradation. Most of the characterized head-to-tail cyclized bacteriocins were discovered through a traditional approach that involved the screening of bacterial isolates for antimicrobial activity and subsequent isolation and characterization of the active molecule. In this study, we performed genome mining using transporter protein sequences associated with experimentally validated head-to-tail cyclized bacteriocins as driver sequences to search for novel bacteriocins. Biosynthetic gene cluster analysis was then performed to select the high probability functional gene clusters. A total of 387 producer strains that encode putative head-to-tail cyclized bacteriocins were identified. Sequence and phylogenetic analyses revealed that this class of bacteriocins is more diverse than previously thought. Furthermore, our genome mining strategy captured hits that were not identified in precursor-based bioprospecting, showcasing the utility of this approach to expanding the repertoire of head-to-tail cyclized bacteriocins. This work sets the stage for future isolation of novel head-to-tail cyclized bacteriocins to serve as possible alternatives to traditional antibiotics and potentially help address the increasing threat posed by resistant pathogens.
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Hui, Wuhan, Fei Ye, Wei Zhang, Congyan Liu, Suigui Wan, and Li Su. "Alterations of Signaling Pathways in Essential Thrombocythemia with Calreticulin Mutation." Blood 128, no. 22 (December 2, 2016): 4286. http://dx.doi.org/10.1182/blood.v128.22.4286.4286.
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Abstract Somatic mutation of calreticulin (CALR) has been found in about 25% patients with essential thrombocythemia (ET), where is the second most common mutated gene after JAK2V617F.Recent data have shown that thrombopoietin receptor MPL function is essential in mutant CALR-mediated cellular transformation. However, the mechanisms for CALR mutant-driven MPN have not been fully elucidated. The goal of this study is to characterize dysregulation of protein expression in ET patients with CALR mutation using Protein Pathway Array (PPA) and to understand possible involvement of signaling pathways related to CALR mutation. This study included 18 ET patients with CALR mutation and 20 ET patients with JAK2V617F mutation and 20 healthy controls. Total proteins were extracted from peripheral blood neutrophil of samples. The expression of 128 proteins was assessed using PPA.PPA is high-throughput proteomic assay, which combines multiplex immunoblot with computational analysis. There were 20 proteins were found to be dysregulated in ET patients with CALR mutation compared with those in healthy controls (p<0.05). Among them, 13 proteins including Erk1/2, PTEN, Rap1, Raf-B, Axin, Cdc42, eIF4B, Bcl-Xl, c-IAP2, NFκB p50, TGF-β, CyclinD1 and SRC-1 were up-regulated in ET patients, while 7 proteins including cPKCα, TDP1, Cdc2, ERβ, Survivin, E-cadherin and p27 were down-regulated in ET patients. To identify the significant pathways affected by these differential expression of the proteins, we analyzed these 20 proteins using Ingenuity Pathways Analysis(IPA) and top 10 canonical pathways were identified. These pathways included PTEN signaling, apoptosis signaling,IL-8 signaling,PI3K-AKT signaling,regulation of the epithelial-mesenchymal transition pathway,ILK signaling,protein kinase A signaling,HGF signaling,IL-12 signaling,cyclins and cell cycle regulation. These results suggest cellular proliferation,apoptosis and cytokine pathways may be involved in CALR mutant-driven ET. To better understand the protein-protein interaction network as well as the major regulators, 20 dysregulated proteins identified by PPA were imported to the IPA and the signal network was built. In this network, core regulators include PTEN,CyclinA, CyclinD1, Erk1/2,E-cadherin,p27.These core regulators may play an important role in pathogenesis of ET with CALR mutation. Furthermore, our results showed a significant overlap in the protein expression patterns between ET patients with CALR mutation and with JAK2V617F mutation. To determine the difference in activated signaling pathways between ET patients with CALR mutation and with JAK2V617F mutation, the protein expression level between these 2 groups were compared and 8 proteins(Erk1/2, TGF-β, CyclinD1, Stat5 , p27, IL-1β, ASCL, HIF1α ) were found to be differentially expressed (p<0.05). These proteins might relate to the signaling pathway of activation by CALR mutation, which was different to JAK-STAT signaling by JAK2V617F mutation. In conclusions, our study suggests that a broad dysregulation of signaling proteins in ET patients with CALR mutation. These findings increase our understanding of CALR mutant characteristics and offer insights into the mechanisms of ET. Disclosures No relevant conflicts of interest to declare.
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Dong, Yunfei, Huiyan Bao, Zhengyu Fang, and Zhi Chen. "Mechanism of cinobufacin anti-metastatic colorectal cancer based on integrated mining of proteomics and bioinformatics." Materials Express 13, no. 7 (July 1, 2023): 1226–33. http://dx.doi.org/10.1166/mex.2023.2452.
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In this study, the effector proteins of anti-metastatic colorectal cancer (CRC) were mined through proteomics based on the preliminary screening of cinobufacin anti-cancer genes using bioinformatics and the role of cinobufacin anti-metastatic CRC was explored. Proteomics was used to analyze the differential expression of proteins in biopsy tissues of patients with metastatic CRC and bioinformatics was adopted to screen for cinobufacin tumor suppressor genes. The effects of proteomics-mined effector protein CyclinD1 on cell proliferation and colony formation were evaluated by MTT assay and colony formation assay. The cinobufacin sensitivity of metastatic CRC cells were also assessed. After proteomic analysis, the common targets of “Cinobufacin-metastatic CRC” were screened out, among which the tumor-associated CyclinD1 was listed as its level was increased in biopsy tissues of patients with metastatic CRC. The preliminary screening of cinobufacin anti-cancer genes based on bioinformatics found that tumor suppressor gene P53 was closely related to metastatic CRC. CyclinD1 had a relation with P53 mRNA. Further studies showed that P53 was the direct target of CyclinD1 and CyclinD1 overexpression enhanced the sensitivity of metastatic CRC cells to cinobufacin. Using bioinformatics-based gene database analysis technology and proteomics mining technology, the differential expression of proteomics in the biopsy tissues of patients with metastatic CRC and the tumor suppressor genes regulated by cinobufacin were identified. CyclinD1 and P53 found by bioinformatics might be biomarkers for metastatic CRC prognosis, providing a new possible molecular target for anticancer therapy.
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Riyajan, Sa-ad, Yasuyuki Tanaka, and Jitladda T. Sakdapipanich. "Preparation of Cyclized Deproteinized Natural Rubber in Latex State via a Combination of Benzotrichloride and Sulfuric Acid System, and Its Properties." Rubber Chemistry and Technology 80, no. 2 (May 1, 2007): 365–77. http://dx.doi.org/10.5254/1.3539412.
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Abstract Partially cyclized deproteinized natural rubber (DPNR) in latex form was successfully prepared by using a combination of sulfuric acid (H2SO4) and benzotrichloride (PhCCl3) in the presence of Terric 320 as a non-ionic surfactant. The main parameters of the cyclization process such as various reaction times, dry rubber contents, concentrations of catalyst and temperatures were investigated. The resulting rubber was subjected to characterization by proton Nuclear Magnetic Resonance (1H-NMR), Fourier-Transform Infrared spectrometer (FTIR), Thermal Gravimetric Analysis (TGA), and Differential Scan Calorimeter (DSC). In addition, the topology of partially cyclized rubber was also analyzed by Transmittance Electron Microscopy (TEM). The mechanism will be also discussed. It was interesting to note that the obtained partially cyclized rubber using this catalyst system contained no gel, which was easily soluble in rubber solvents. This is different from the partially cyclized rubber obtained from the other methods. Through, using structural characterization, it was found that the PhCCl3 linked onto the rubber chain. It was also found that the thermal stability of this cyclized rubber was better than that of normal rubber. The efficiency of cyclization in this system could be increased by an increase of PhCCl3 concentration.