检索结果-内蒙古大学图书馆

Cdkn1a silencing restores myoblast differentiation by inducing selective apoptosis in senescent cells

Cellular and Molecular Biology Letters 2025年第1期30卷 1-21页

作者： Kim, Sujin Gu, Bonsang So, Chan-Young Mantik, Keren Esther Kristina Jung, Seung-Hyun Moon, Sohee Park, Dong-Ho Kwak, Hyo-Bum Cho, Jinkyung Cho, Eun-Jeong Lee, Jae-Seon Kang, Ju-Hee Department of Pharmacology Inha University College of Medicine 100 Inha-Ro Michuhol-Gu Incheon 22212 South Korea Research Center for Controlling Intercellular Communication Inha University College of Medicine Incheon 22212 South Korea Program in Biomedical Science and Engineering Inha University Incheon South Korea Department of Biochemistry College of Medicine The Catholic University of Korea Seoul South Korea Integrated Research Center for Genomic Polymorphism College of Medicine The Catholic University of Korea Seoul South Korea Department of Medical Sciences Graduate School of The Catholic University of Korea Seoul South Korea Department of Kinesiology Inha University Incheon South Korea College of Sport Science Sungkyunkwan University Suwon South Korea Department of Molecular Medicine Inha University College of Medicine 100 Inha-Ro Michuhol-Gu Incheon 22212 South Korea

Background: Sarcopenia, characterized by a progressive loss of skeletal muscle mass and function, is associated with the accumulation of senescent muscle stem cells, which impair muscle regeneration and contributes to the decline in muscle health. Cdkn1a, which encodes p21, is a well-known marker of cellular senescence. However, it remains unclear whether p21 inhibition eliminates senescent myoblasts and restores the differentiation capacity. Methods: We performed transcriptomic analysis to identify genes related to aging-induced sarcopenia using 21 month-old Sprague–Dawley rats. To investigate the specific role of Cdkn1a gene in muscle aging, we used an in vitro model of ceramide-induced senescence in myoblasts, which was verified by the upregulation of p21 and increased senescence-associated beta-galactosidase (SA-β-gal) staining. To inhibit p21, we treated myoblasts with small interfering RNA (siRNA) targeting Cdkn1a. Using fluorescence-activated cell sorting, we separated subpopulations of cells with high or low caspase 3/7 activity. Protein expression related to myogenesis, muscle atrophy, protein synthesis, and apoptosis were quantified by western blotting. Results: In our transcriptomic analysis, we identified Cdkn1a as an upregulated gene in both the soleus and white gastrocnemius muscles of aged rats, among 36 commonly upregulated genes. The upregulation of Cdkn1a appears to be linked to mitochondrial dysfunction and cellular senescence, underscoring its significance in sarcopenia pathogenesis. C2-ceramide treatment effectively induced senescence, as evidenced by increased p21 expression, enhanced SA-β-gal staining, decreased myogenesis, and increased apoptosis. Knockdown of p21 in ceramide-treated myoblasts significantly reduced SA-β-gal-positive cells, restored cell proliferation, reduced the expression of senescence-associated cytokines (i.e., interleukin (IL)-6 and tumor necrosis factor (TNF)-α), and selectively induced apoptosis in the senescent cell p

关键词： Cdkn1a Myogenesis p21 Sarcopenia Senescence Senolysis

来源：评论

学校读者我要写书评

暂无评论

Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications

引用

Molecular Cancer 2025年第1期24卷 1-61页

作者： Pham, Trang Thao Quoc Kuo, Yung-Che Chang, Wei-Ling Weng, Hao-Jui Huang, Yen-Hua International Ph.D. Program in Cell Therapy and Regenerative Medicine College of Medicine Taipei Medical University Taipei Taiwan TMU Research Center for Cell Therapy and Regeneration Medicine Taipei Medical University Taipei Taiwan Department of Dermatology Taipei Medical University-Shuang Ho Hospital New Taipei City Taiwan Department of Dermatology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Graduate Institute of Clinical Medicine College of Medicine Taipei Medical University Taipei Taiwan Department of Biochemistry and Molecular Cell Biology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei Taiwan

The niche microenvironment plays a crucial role in regulating the fate of normal skin stem cells (SSCs) and cancer stem cells (CSCs). Therapeutically targeting the CSC niche holds promise as an effective strategy; however, the dual effects of shared SSC niche signaling in CSCs have contributed to the aggressive characteristics of tumors and poor survival rates in skin cancer patients. The lack of a clear underlying mechanism has significantly hindered drug development for effective treatment. This article explores recent advances in understanding how niche factors regulate cell fate determination between skin stem cells and skin CSCs, along with their clinical implications. The dual roles of key components of the adhesive niche, including the dermo-epidermal junction and adherens junction, various cell types—especially immune cells and fibroblasts—as well as major signaling pathways such as Sonic hedgehog (Shh), Wingless-related integration site (Wnt)/β-catenin, YAP (Yes-associated protein)/TAZ (transcriptional coactivator with PDZ-binding motif), and Notch, are highlighted. Additionally, recent advances in clinical trials and drug development targeting these pathways are discussed. Overall, this review provides valuable insights into the complex interactions between skin cancer stem cells and their microenvironment, laying the groundwork for future research and clinical strategies.

关键词：

来源：评论

学校读者我要写书评

暂无评论

GAMMA-FLUOROADENOSINE TRIPHOSPHATE - SYNTHESIS, PROPERTIES, AND INTERACTION WITH MYOSIN AND HEAVY MEROMYOSIN

引用

biochemistry 1972年第15期11卷 2863-&页

作者： HALEY, B YOUNT, RG Departments of Chemistry and Agricultural Chemistry Graduate Program in Biochemistry Washington State University Pullman Washington 99163 United States

The adenosine triphosphate analog, ?-fluoroadeno-sine 5′-triphosphate (FATP), has been synthesized by the reaction of P1-diphenyl P2-fluoropyrophosphate with adenosine diphosphate and isolated as the trisodium salt in 30% yields. FATP is stable (<4% loss) in solutions, pH 7.4, 25°, for at least 2 days and as the sodium salt at —20° for several months. FATP binds Ca2+, Mg2+, and Mn2+ with affinity constants of 242, 200, and 505, respectively, at pH 8.2, 0.1 m NaCl while comparable constants measured for ATP were 5150, 8600, and 46,000. FATP was not a substrate for myosin, heavy meromyosin, hexokinase, or Escherchia coli alkaline phosphatase. It was about 0.4% as effective at ATP in the pyrophosphate-exchange assay of the mixed aminoacyl-tRNA synthetases from Bacillus brevis. Snake venom phosphodiesterase cleaved FATP to AMP and fluoropyrophosphate;this latter product established that the fluorophosphate was on the β-phosphate of adenosine diphosphate. FATP would not support the contraction of glycerol-extracted muscle fibers or prevent ATP-induced contraction. It did not irreversibly inhibit heavy meromyosin or myosin under a variety of conditions. FATP does competitively inhibit heavy meromyosin catalyzed ATP cleavage with Kimg2+ = 4.3 X 10-4 m and Kica2+ + = 3.4 X 10-3 m. FATP protects myosin against heat inactivation almost as well (50%) as ATP in the presence of Mg2+ but has no effect when Ca2+ is used. The stability and properties of FATP indicate it should be useful as an analog to minic HATP3-. The fluorine nuclear magnetic resonance of FATP should be a useful probe of the binding sites of ATP-requiring enzymes. © 1972, American Chemical Society. All rights reserved.

关键词：

来源：评论

学校读者我要写书评

暂无评论

DIFFERENT INFLUENCES OF 2 FRACTIONS OF LUNG CYTOCHROME-B5 ON RECONSTITUTED LUNG BENZPHETAMINE N-DEMETHYLASE SYSTEM

引用

INTERNATIONAL JOURNAL OF biochemistry & CELL BIOLOGY 1995年第10期27卷 1095-1105页

作者： ARINC, E ADALI, O PASHA, RPK BASARAN, N Joint Graduate Program in Biochemistry Department of Biology Middle East Technical University Inonu Bulvari Ankara 06531 Turkey

Chromatography of lung microsomal cytochrome b5 obtained from DEAE-cellulose columns, yielded two distinct cytochrome b5 fractions, These cytochrome b5 fractions were further purified by Sephadex G-100 gel filtration chromatography. The specific cytochrome b5 content of fraction 1 and fraction 2 was found to be 16.5 and 16.4 nmol/mg protein respectively. Both fractions were free of cytochrome P-450, NADPH-cytochrome P-450 reductase and NADH-cytochrome b5 reductase activities. The effects of lung cytochrome b5 (fraction 1 and fraction 2) and liver cytochrome b5 on benzphetamine N-demethylase activity were examined, Four different reconstitution systems were used, Lung cytochrome b5 fraction 2 and liver cytochrome b5 stimulated N-demethylase activity in all four systems when b5:P-450 molar ratio was low, i.e. 0.25 or 0.5, Both cytochrome b5 samples inhibited N-demethylase activity when b5:P-450 ratio exceeded 1:1 molar ratio, In contrast lung cytochrome b5 fraction 1 stimulated N-demethylase activity in all four systems, Maximal enhancement of the activity was obtained when b5:P-450 ratio was 0.5. The greatest increase in N-demethylation activity was observed in the reconstitution system with the lowest concentration of cytochrome P-450 reductase, conditions which most closely resemble intact microsomes.

关键词： CYTOCHROME B5 LUNG CYTOCHROME P-450 BENZPHETAMINE N-DEMETHYLASE

来源：评论

学校读者我要写书评

暂无评论

Structure of the human TWIK-2 potassium channel and its inhibition by pimozide

引用

Proceedings of the National Academy of Sciences of the United States of America 2025年第19期122卷 e2425709122页

作者： Khanra, Nandish K. Wang, Chongyuan Delgado, Bryce D. Long, Stephen B. Structural Biology Program Memorial Sloan Kettering Cancer Center New York 10065 NY United States Graduate Program in Biochemistry and Structural Biology Cell and Developmental Biology and Molecular Biology Weill Cornell Medicine Graduate School of Medical Sciences New York 10065 NY United States

The potassium channel TWIK-2 is crucial for ATP-induced activation of the NLRP3 inflammasome in macrophages. The channel is a member of the two-pore domain potassium (K2P) channel superfamily and an emerging therapeutic target to mitigate severe inflammatory injury involving NLRP3 activation. We report the cryo-EM structure of human TWIK-2. In comparison to other K2P channels, the structure reveals an unusual “up” conformation of Tyr111 in the selectivity filter and a resulting SF1-P1 pocket behind the filter. Density for acyl chains is present in fenestrations within the transmembrane region that connects the central cavity of the pore to the lipid membrane. Despite its importance as a drug target, limited pharmacological tools are available for TWIK-2. A previous study suggested that the FDA-approved small molecule pimozide might inhibit TWIK-2. Using a reconstituted system, we show that pimozide directly inhibits the channel and we determine a cryo-EM structure of a complex with the drug. Pimozide displaces the acyl chains within the fenestrations and binds below the selectivity filter where it would impede ion permeation. The drug may access its binding site by lateral diffusion in the membrane, suggesting that other hydrophobic small molecules could have utility for inhibiting TWIK-2. The work defines the structure of TWIK-2 and provides a structural foundation for development of more specific inhibitors with potential utility as anti-inflammatory drugs. Copyright © 2025 the Author(s).

关键词： K2P channel K2P6 NLRP3 inflammasome potassium channel therapeutic

来源：评论

学校读者我要写书评

暂无评论

BPS2025 - Disaggregation of biomolecular condensates by molecular chaperones is heterogeneous at the single-condensate level

引用

Biophysical Journal 2025年第3期124卷 415a-415a页

作者： Diangen Lin Kyle M. Lin David A. Drummond Allison H. Squires Harvard Graduate Program in Biophysics Harvard University Cambridge MA USA Graduate Program in Biophysical Sciences Medical Scientist Training Program University of Chicago Chicago IL USA Department of Biochemistry and Molecular Biology and Department of Medicine Section of Genetic Medicine University of Chicago Chicago IL USA Pritzker School of Molecular Engineering University of Chicago Chicago IL USA

来源：评论

学校读者我要写书评

暂无评论

The transport of iron by rat intestine

引用

BBA - Biomembranes 1967年第5期135卷 979-990页

作者： Helbock, Harold J. Saltman, Paul The Graduate Program in Biochemistry University of Southern California Los Angeles CA United States

To define more clearly the mechanisms operate in the transport of iron by intestinal mucosa, the short-circuit technique has been applied to isolated sections of small intestine of rat. Parallel experiments have been carried out in vivo using ligated sections of the small intestine in the intact rat. Low-molecular-weight chelates are necessary to maintain iron in a soluble and permeable from. Although the rate of mucosal to serosal transport appears to be directly dependent upon the concentration of iron chelate presented to the cell, a membrane-bound facilitating carrier also participates in the process. Evidence is presented for an active serosal to mucosal component for iron transport. Metabolic inhibitors, low temperatures and anaerobiosis abolish the net serosal to mucosal flux. The chemical nature of the chelate directly affects the rate of transmembrane transport as well as the tissue distribution of the iron molecule. Iron deficiency anemia causes both a decrease in the serosal to mucosal iron flux and an increase in the mucosal to serosal component. These factors appear to be responsible for the enhanced uptake of iron observed in anemic animals. © 1967.

关键词： M → S flux from mucosal to serosal surface S → M flux from serosal to mucosal surface

来源：评论

学校读者我要写书评

暂无评论

Peanuts (Arachis hypogaea L.) in food industry and their benefits for human health – A review of the current literature

引用

Journal of Food Composition and Analysis 2025年 143卷

作者： Machado, Nathalia Mendes Nunes, Yandra Cervelim de Lima, Enzo Pereira Chehadi, Amanda Chabrour Otoboni, Alda M.M.B. Miola, Vitor Fernando Bordin Nicolau, Cláudia C.T. Fiorini, Adriana M.R. Oshiiwa, Marie Laurindo, Lucas Fornari Barbalho, Sandra Maria Department of Biochemistry and Pharmacology School of Medicine University of Marília (UNIMAR) São Paulo Marília 17525-902 Brazil Department of Biochemistry and Nutrition School of Food and Technology of Marília (FATEC) São Paulo Marília 17500-000 Brazil Post-graduate Program in Structural and Functional Interactions in Rehabilitation University of Marília (UNIMAR) São Paulo Marília 17525-902 Brazil Research Coordination - UNIMAR Charitable Hospital São Paulo Marília 17525-902 Brazil

Peanut (Arachis hypogaea L.) ranks fourth among the oil seeds worldwide and can be consumed raw, cooked, roasted, as flour, butter, or crushed into edible oil. The main use of peanuts grown in the world is the production of edible oil that can be used in cooking thanks to its mild flavor and the possibility of being incorporated into other food preparations. Peanut oil is rich in vitamins and fatty acids, mainly palmitic, oleic, and linoleic acids, and traces of linolenic fatty acid. The seeds, skin, and shells possess bioactive compounds such as ellagic acid, chlorogenic acid, gallic acid, catechin, daidzein, genistein, epicatechin, kaempferol, luteolin, and resveratrol. The presence of bioactive compounds in the seeds, skin, shell, and food products may represent a sustainable and cost-effective dietary intervention with a vast potential to be used in the prevention or even in the treatment of chronic degenerative diseases, including diabetes, obesity, cardiovascular and neurodegenerative diseases, and cancer. A significant concern related to peanut seeds and by-products consumption is allergenicity. Moreover, the presence of aflatoxin is a global concern as it has a strong link with the development of cancer. © 2025 Elsevier Inc.

关键词： Arachis hypogaea By-products Food industry Inflammation New products Oxidative stress Peanut shell Peanut skin

来源：评论

学校读者我要写书评

暂无评论

The interaction of cadmium and zinc ions with thiol-substituted dextrans

引用

Bioinorganic Chemistry 1971年第1期1卷 65-78页

作者： P. Gaber, Bruce L. Fluharty, Arvan Graduate Program in Biochemistry The University of Southern California Los Angeles CA United States

Water-soluble, inert polymers with attached monothiol ligands were prepared and used to determine the binding parameters of the reagents normally accepted as being diagnostic for enzymatic dithiols. The measurements were carried out by procedures which permitted direct comparison with enzyme inhibition data. The monothiol polymers were N-(N-acetyl) homocysteinyl aminoethoxy dextran, N-thiolbutyryl aminoethoxy dextran, and O-thiolsuccinyl dextran. The binding parameters of the monothiol polymers with cadmium and zinc were determined by equilibrium dialysis and by spectrophotometric techniques. Cadmium is bound by monothiol polymers approximately two orders of magnitude more firmly than zinc. At low free metal ion concentrations, a complex of three thiol groups per metal ion appears to be formed. As the metal ion concentration is increased, this 3:1 complex reforms into one characterized by a 2:1 stoichiometry. There are no major differences in the binding properties of N-(N-acetyl) homocysteinyl aminoethoxy dextran, N-thiolbutryl aminoethoxy dextran, and O-thiolsuccinyl dextran. © 1971.

关键词： Enzyme Diothiol Criteria Thiol-Substituted Dextrans Cadmium Ion Zinc Ion Polythiol Complex Equilibrium Dialysis Spectrophotometric Titration Induced Polythiol Ligand Aminoethoxy Dextran N-(N-Acetyl)

来源：评论

学校读者我要写书评

暂无评论

N-LIPOYL GLUCOSAMINE AND N-LIPOYL GLUCOSAMINITOL - SUBSTRATES FOR LIPOYL DEHYDROGENASE

引用

ARCHIVES OF biochemistry AND BIOPHYSICS 1969年第2期134卷 346-&页

作者： FLUHARTY, AL ADELSON, GL GABER, BP The Department of Biological Sciences and the Graduate Program in Biochemistry The University of Southern California Los Angeles California 90007 U.S.A.

N - dl -Lipoyl- d -glucosamine and N - dl -lipoyl- d -glucosaminitol were prepared and tested as substrates for lipoyl dehydrogenase (reduced nicotinamide adenine dinucleotide: Lipoamide oxidoreductase, EC 1.6.4.3). It was anticipated that such lipoateamino carbohydrate derivatives would be superior substrates for the enzyme, having greater water solubility than lipoamide, and greater enzyme affinity than lipoate and other anionic derivatives. N - dl -Lipoyl- d -glucosamine proved to be only sparingly soluble in water although both derivatives were more soluble than dl -lipoamide. Both compounds were enzymatically reduced by NADH, but they were no better as substrates for lipoyl dehydrogenase than lipoate anion. Saturation kinetics were not observed indicating that enzyme-substrate interaction was rate limiting. Conventional saturation kinetics were obtained with the dithiol forms of these lipoate derivatives serving as electron donors for the enzymatic reduction of NAD, but their effectiveness as substrates was lower than with dl -dihydrolipoamide. It is suggested that the active center of lipoyl dehydrogenase is hydrophobic and as a consequence those derivatives with a highly hydrated function near the lipoyl carbonyl group are inferior substrates.

关键词：

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：