TY - JOUR AU - Bairamukov, V.Y. AU - Kovalev, R.A. AU - Ankudinov, A.V. AU - Pantina, R.A. AU - Fedorova, N.D. AU - Bukatin, A.S. AU - Grigoriev, S.V. AU - Varfolomeeva, E.Y. TI - Alterations in the chromatin packaging, driven by transcriptional activity, revealed by AFM JF - BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS J2 - BBA-GEN SUBJECTS VL - 1868 PY - 2024 IS - 4 SN - 0304-4165 DO - 10.1016/j.bbagen.2024.130568 UR - https://m2.mtmt.hu/api/publication/34694531 ID - 34694531 N1 - Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of NRC “Kurchatov Institute”, 1, Orlova Roshcha, Gatchina, 188300, Russian Federation The Ioffe Physical-Technical Institute of the Russian Academy of Sciences, 26, Politekhnicheskaya, Saint Petersburg, 194021, Russian Federation Alferov Saint Petersburg National Research Academic University of the Russian Academy of Sciences, 8/3, Khlopina St., Saint Petersburg, 194021, Russian Federation Export Date: 29 February 2024 CODEN: BBGSB Correspondence Address: Bairamukov, V.Y.; Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of NRC “Kurchatov Institute”, 1, Orlova Roshcha, Russian Federation; email: bayramukov_vy@pnpi.nrcki.ru Chemicals/CAS: DNA topoisomerase, 80449-01-0; DNA topoisomerase (ATP hydrolysing) Funding details: Russian Science Foundation, RSF, 20–12-00188 Funding text 1: The reported study was funded by the Russian Science Foundation under Grant 20–12-00188 . AB - Background: The gene expression differs in the nuclei of normal and malignant mammalian cells, and transcription is a critical initial step, which defines the difference. The mechanical properties of transcriptionally active chromatin are still poorly understood. Recently we have probed transcriptionally active chromatin of the nuclei subjected to mechanical stress, by Atomic Force Microscopy (AFM) [1]. Nonetheless, a systematic study of the phenomenon is needed. Methods: Nuclei were deformed and studied by AFM. Non-deformed nuclei were studied by fluorescence confocal microscopy. Their transcriptional activity was studied by RNA electrophoresis. Results: The malignant nuclei under the study were stable to deformation and assembled of 100–300 nm beads-like units, while normal cell nuclei were prone to deformation. The difference in stability to deformation of the nuclei correlated with DNA supercoiling, and transcription-depended units were responsive to supercoils breakage. The inhibitors of the topoisomerases I and II disrupted supercoiling and made the malignant nucleus prone to deformation. Cell nuclei treatment with histone deacetylase inhibitors (HDACIs) preserved the mechanical stability of deformed malignant nuclei and, at the same time, made it possible to observe chromatin decondensation up to 20–60 nm units. The AFM results were supplemented with confocal microscopy and RNA electrophoresis data. Conclusions: Self-assembly of transcriptionally active chromatin and its decondensation, driven by DNA supercoiling-dependent rigidity, was visualized by AFM in the mechanically deformed nuclei. General significance: We demonstrated that supercoiled DNA defines the transcription mechanics, and hypothesized the nuclear mechanics in vivo should depend on the chromatin architecture. © 2024 LA - English DB - MTMT ER - TY - JOUR AU - Somee, L.R. AU - Barati, A. AU - Shahsavani, M.B. AU - Hoshino, M. AU - Hong, J. AU - Kumar, A. AU - Moosavi-Movahedi, A.A. AU - Amanlou, M. AU - Yousefi, R. TI - Understanding the structural and functional changes and biochemical pathomechanism of the cardiomyopathy-associated p.R123W mutation in human αB-crystallin JF - BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS J2 - BBA-GEN SUBJECTS VL - 1868 PY - 2024 IS - 4 SN - 0304-4165 DO - 10.1016/j.bbagen.2024.130579 UR - https://m2.mtmt.hu/api/publication/34634517 ID - 34634517 N1 - Protein Chemistry Laboratory (PCL), Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran Department of Biology, Shiraz University, Shiraz, Iran Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan School of Life Sciences, Henan University, Kaifen, China Department of Biosciences and Bioengineering, IIT Bombay, Mumbai, Powai, India Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Export Date: 19 February 2024 CODEN: BBGSB Correspondence Address: Yousefi, R.; Protein Chemistry Laboratory (PCL), Iran; email: yousefi.reza@ut.ac.ir LA - English DB - MTMT ER - TY - JOUR AU - Elbeltagi, Shehab AU - Saeedi, Ahmad M. AU - Eldin, Zienab E. AU - Alfassam, Haifa E. AU - Alharbi, Hanan M. AU - Madkhali, Nawal AU - Shakor, Abo Bakr Abdel AU - Abd El-Aal, Mohamed TI - Biosynthesis, characterization, magnetic hyperthermia, and in vitro toxicity evaluation of quercetin-loaded magnetoliposome lipid bilayer hybrid system on MCF-7 breast cancer JF - BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS J2 - BBA-GEN SUBJECTS VL - 1868 PY - 2024 IS - 3 PG - 12 SN - 0304-4165 DO - 10.1016/j.bbagen.2023.130543 UR - https://m2.mtmt.hu/api/publication/34613076 ID - 34613076 AB - Novel biocompatible and effective hyperthermia (HT) treatment materials for breast cancer therapeutic have recently attracting researchers, because of their effective ablation of cancer cells and negligible damage to healthy cells. Magnetoliposome (MLs) have numerous possibilities for utilize in cancer treatment, including smart drug delivery (SDD) mediated through alternating magnetic fields (AMF). In this work, magnesium ferrite (MgFe2O4) encapsulated with liposomes lipid bilayer (MLs), Quercetin (Q)-loaded MgFe2O4@Liposomes (Q-MLs) nano-hybrid system were successfully synthesized for magnetic hyperthermia (MHT) and SDD applications. The hybrid system was well-investigated by different techniques using X-ray diffraction (XRD), Fourier transforms infrared spectroscopy (FT-IR), Energy dispersive X-ray (EDX), Vibrating sample magnetometer (VSM), Transmission electron microscope (TEM), and Zeta Potential (ZP). The characterization results confirmed the improving quercetin-loading on the MLs surface. TEM analysis indicated the synthesized MgFe2O4, MLs, and QMLs were spherical with an average size of 23.7, 35.5, and 329.5 nm, respectively. The VSM results revealed that the MgFe2O4 exhibit excellent and effective saturation magnetization (MS) (40.5 emu/g). Quercetin drug loading and entrapment efficiency were found to be equal to 2.1 +/- 0.1% and 42.3 +/- 2.2%, respectively. The in-vitro Q release from Q-loaded MLs was found 40.2% at pH 5.1 and 69.87% at pH 7.4, verifying the Q-loading pH sensitivity. The MLs and Q-MLs hybrid system as MHT agents exhibit specific absorption rate (SAR) values of 197 and 205 W/g, correspondingly. Furthermore, the Q-MLs cytotoxicity was studied on the MCF-7 breast cancer cell line, and the obtained data demonstrated that the Q-MLs have a high cytotoxicity effect compared to MLs and free Q. LA - English DB - MTMT ER - TY - JOUR AU - Panghal, Archna AU - Flora, S. J. S. TI - Nanotechnology in the diagnostic and therapy for Alzheimer's disease JF - BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS J2 - BBA-GEN SUBJECTS VL - 1868 PY - 2024 IS - 3 PG - 19 SN - 0304-4165 DO - 10.1016/j.bbagen.2024.130559 UR - https://m2.mtmt.hu/api/publication/34590294 ID - 34590294 AB - Alzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by beta-amyloid plaque, intraneuronal tangles, significant neuronal loss and cognitive deficit. Treatment in the early stages of the disease is crucial for preventing or perhaps reversing the neurodegeneration in the AD cases. However, none of the current diagnostic procedures are capable of early diagnosis of AD. Further, the available treatments merely provide symptomatic alleviation in AD and do not address the underlying illness. Therefore, there is no permanent cure for AD currently. Better therapeutic outcomes need the optimum drug concentration in the central nervous system (CNS) by traversing blood-brain-barrier (BBB). Nanotechnology offers enormous promise to transform the treatment and diagnostics of neurodegenerative diseases. Nanotechnology based diagnostic tools, drug delivery systems and theragnostic are capable of highly sensitive molecular detection, effective drug targeting and their combination. Significant work has been done in this area over the last decade and prospective results have been obtained in AD therapy. This review explores the various applications of nanotechnology in addressing the varied facets of AD, ranging from early detection to therapeutic interventions. This review also looks at how nanotechnology can help with the development of disease-modifying medicines, such as the delivery of anti-amyloid, anti-tau, cholinesterase inhibitors, antioxidants and hormonal drugs. In conclusion, this paper discusses the role of nanotechnology in the early detection of AD, effective drug targeting to the CNS and theragnostic applications in the management of AD. LA - English DB - MTMT ER - TY - JOUR AU - Mobasher, M. AU - Ansari, R. AU - Castejon, A.M. AU - Barar, J. AU - Omidi, Y. TI - Advanced nanoscale delivery systems for mRNA-based vaccines JF - BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS J2 - BBA-GEN SUBJECTS VL - 1868 PY - 2024 IS - 3 PG - 20 SN - 0304-4165 DO - 10.1016/j.bbagen.2024.130558 UR - https://m2.mtmt.hu/api/publication/34523181 ID - 34523181 N1 - Export Date: 22 January 2024 CODEN: BBGSB Correspondence Address: Omidi, Y.; Department of Pharmaceutical Sciences, United States; email: yomidi@nova.edu Funding details: Nova Southeastern University, NSU Funding text 1: The authors would like to express their gratitude for the support received through the HPD Grant (#334643), generously provided by the Barry and Judy Silverman College of Pharmacy at Nova Southeastern University. AB - The effectiveness of messenger RNA (mRNA) vaccines, especially those designed for COVID-19, relies heavily on sophisticated delivery systems that ensure efficient delivery of mRNA to target cells. A variety of nanoscale vaccine delivery systems (VDSs) have been explored for this purpose, including lipid nanoparticles (LNPs), liposomes, and polymeric nanoparticles made from biocompatible polymers such as poly(lactic-co-glycolic acid), as well as viral vectors and lipid-polymer hybrid complexes. Among these, LNPs are particularly notable for their efficiency in encapsulating and protecting mRNA. These nanoscale VDSs can be engineered to enhance stability and facilitate uptake by cells. The choice of delivery system depends on factors like the specific mRNA vaccine, target cell types, stability requirements, and desired immune response. In this review, we shed light on recent advances in delivery mechanisms for self-amplifying RNA (saRNA) vaccines, emphasizing groundbreaking studies on nanoscale delivery systems aimed at improving the efficacy and safety of mRNA/saRNA vaccines. © 2024 Elsevier B.V. LA - English DB - MTMT ER - TY - JOUR AU - Nie, G. AU - Chen, S. AU - Song, Q. AU - Zou, D. AU - Li, M. AU - Tang, X. AU - Deng, Y. AU - Huang, B. AU - Yang, M. AU - Lv, G. AU - Zhang, Y. TI - DHX33 mediates p53 to regulate mevalonate pathway gene transcription in human cancers JF - BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS J2 - BBA-GEN SUBJECTS VL - 1868 PY - 2024 IS - 3 SN - 0304-4165 DO - 10.1016/j.bbagen.2023.130547 UR - https://m2.mtmt.hu/api/publication/34503056 ID - 34503056 N1 - Shenzhen KeYe Life Technologies Co., Ltd, Guangdong, Shenzhen, 518000, China Southern University of Science and Technology, Shenzhen, China Department of Gastrointestinal Surgery, Peking University Shenzhen Hospital, China Shenzhen College of International Education, Shenzhen, China Export Date: 15 January 2024 CODEN: BBGSB Correspondence Address: Zhang, Y.; Shenzhen KeYe Life Technologies Co., Room 501, Building #3, Salubris Pharmaceutical & Biomedical Industry Park, 8 Juliu Road, Pingshan District, China; email: zhangyd@keye-life.com Correspondence Address: Lv, G.; Department of Gastrointestinal Surgery, Guangdong, China; email: lvguoqing1970@gmail.com Chemicals/CAS: cholesterol, 57-88-5; interferon induced helicase C domain containing protein 1; mevalonic acid, 150-97-0; RNA helicase Funding text 1: This work was supported by funds from KeYe Life Technologies Co., Ltd. AB - Tumor suppressor p53 is frequently null or mutated in human cancers. Here in this study, DHX33 protein was found to be induced in p53 null cells in vitro, and in p53 mutant lung tumorigenesis in vivo. Cholesterol metabolism through mevalonate pathway is pivotal for cell proliferation and is frequently altered in human cancers. Mice carrying mutant p53 and KrasG12D alleles showed upregulation of mevalonate pathway gene expression. However upon DHX33 loss, their upregulation was significantly debilitated. Additionally, in many human cancer cells, DHX33 knockdown caused inhibition of mavelonate pathway gene transcription. We propose DHX33 locates downstream of mutant p53 and Ras to regulate mevalonate pathway gene transcription and thereby supports cancer development in vivo. © 2023 Elsevier B.V. LA - English DB - MTMT ER - TY - JOUR AU - Gorman, Brittney L. AU - Torti, Suzy V. AU - Torti, Frank M. AU - Anderton, Christopher R. TI - Mass spectrometry imaging of metals in tissues and cells: Methods and biological applications JF - BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS J2 - BBA-GEN SUBJECTS VL - 1868 PY - 2024 IS - 2 PG - 8 SN - 0304-4165 DO - 10.1016/j.bbagen.2023.130329 UR - https://m2.mtmt.hu/api/publication/34621618 ID - 34621618 LA - English DB - MTMT ER - TY - JOUR AU - Sundar, G. Vivek Hari AU - Madhu, Aravind AU - Archana, A. AU - Shivaprasad, P. V. TI - Plant histone variants at the nexus of chromatin readouts, stress and development JF - BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS J2 - BBA-GEN SUBJECTS VL - 1868 PY - 2024 IS - 2 PG - 11 SN - 0304-4165 DO - 10.1016/j.bbagen.2023.130539 UR - https://m2.mtmt.hu/api/publication/34616308 ID - 34616308 AB - Histones are crucial proteins that are involved in packaging the DNA as condensed chromatin inside the eukaryotic cell nucleus. Rather than being static packaging units, these molecules undergo drastic variations spatially and temporally to facilitate accessibility of DNA to replication, transcription as well as wide range of gene regulatory machineries. In addition, incorporation of paralogous variants of canonical histones in the chromatin is ascribed to specific functions. Given the peculiar requirement of plants to rapidly modulate gene expression levels on account of their sessile nature, histones and their variants serve as additional layers of gene regulation. This review summarizes the mechanisms and implications of distribution, modifications and differential incorporation of histones and their variants across plant genomes, and outlines emerging themes. LA - English DB - MTMT ER - TY - JOUR AU - Brooks III, Charles L. AU - MacKerell Jr, Alexander D. AU - Post, Carol B. AU - Nilsson, Lennart TI - Biomolecular dynamics in the 21st century JF - BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS J2 - BBA-GEN SUBJECTS VL - 1868 PY - 2024 IS - 2 PG - 5 SN - 0304-4165 DO - 10.1016/j.bbagen.2023.130534 UR - https://m2.mtmt.hu/api/publication/34601608 ID - 34601608 AB - The relevance of motions in biological macromolecules has been clear since the early structural analyses of proteins by X-ray crystallography. Computer simulations have been applied to provide a deeper understanding of the dynamics of biological macromolecules since 1976, and are now a standard tool in many labs working on the structure and function of biomolecules. In this mini-review we highlight some areas of current interest and active development for simulations, in particular all-atom molecular dynamics simulations. LA - English DB - MTMT ER - TY - JOUR AU - Duff, Stephen M. G. AU - Zhang, Meiying AU - Zinnel, Fred AU - Rydel, Timothy AU - Taylor, Christina M. AU - Chen, Danqi AU - Tilton, Gregory AU - Mamanella, Patricia AU - Duda, David AU - Wang, Yanfei AU - Xiang, Bosong AU - Karunanandaa, Balasulojini AU - Varagona, Rita AU - Chittoor, Jaishree AU - Qi, Qungang AU - Hall, Erin AU - Garvey, Graeme AU - Zeng, Jiamin AU - Zhang, Jun AU - Li, Xin AU - White, Tommi AU - Jerga, Agoston AU - Haas, Jeff TI - Structural and functional characterization of triketone dioxygenase from Oryza Sativa JF - BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS J2 - BBA-GEN SUBJECTS VL - 1868 PY - 2024 IS - 2 PG - 13 SN - 0304-4165 DO - 10.1016/j.bbagen.2023.130504 UR - https://m2.mtmt.hu/api/publication/34580245 ID - 34580245 AB - The transgenic expression of rice triketone dioxygenase (TDO; also known as HIS1) can provide protection from triketone herbicides to susceptible dicot crops such as soybean. Triketones are phytotoxic inhibitors of plant hydroxyphenylpyruvate dioxygenases (HPPD). The TDO gene codes for an iron/2-oxoglutarate-dependent oxidoreductase. We obtained an X-ray crystal structure of TDO using SeMet-SAD phasing to 3.16 angstrom resolution. The structure reveals that TDO possesses a fold like that of Arabidopsis thaliana 2-oxoglutarate-iron-dependent oxygenase anthocyanidin synthase (ANS). Unlike ANS, this TDO structure lacks bound metals or cofactors, and we propose this is because the disordered flexible loop over the active site is sterically constrained from folding properly in the crystal lattice. A combination of mass spectrometry, nuclear magnetic resonance, and enzyme activity studies indicate that rice TDO oxidizes mesotrione in a series of steps; first producing 5-hydroxy-meso-trione and then oxy-mesotrione. Evidence suggests that 5-hydroxy-mesotrione is a much weaker inhibitor of HPPD than mesotrione, and oxy-mesotrione has virtually no inhibitory activity. Of the close homologues which have been tested, only corn and rice TDO have enzymatic activity and the ability to protect plants from mesotrione. Correlating sequence and structure has identified four amino acids necessary for TDO activity. Introducing these four amino acids imparts activity to a mesotrione-inactive TDO-like protein from sorghum, which may expand triketone herbicide resistance in new crop species. LA - English DB - MTMT ER -