@article{MTMT:34694531, title = {Alterations in the chromatin packaging, driven by transcriptional activity, revealed by AFM}, url = {https://m2.mtmt.hu/api/publication/34694531}, author = {Bairamukov, V.Y. and Kovalev, R.A. and Ankudinov, A.V. and Pantina, R.A. and Fedorova, N.D. and Bukatin, A.S. and Grigoriev, S.V. and Varfolomeeva, E.Y.}, doi = {10.1016/j.bbagen.2024.130568}, journal-iso = {BBA-GEN SUBJECTS}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS}, volume = {1868}, unique-id = {34694531}, issn = {0304-4165}, abstract = {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}, keywords = {TRANSCRIPTION; ARTICLE; ARTICLE; MOUSE; FLUORESCENCE; human; controlled study; Chromatin; Chromatin; Cell Nucleus; nonhuman; animal cell; ELECTROPHORESIS; AFM; atomic force microscopy; Gene Expression; human cell; drug mechanism; confocal microscopy; genetic transcription; mechanical stress; mammal cell; Chromatin condensation; DNA topoisomerase; DNA topoisomerase; histone modification; histone modification; histone modification; Histone deacetylase inhibitor; Histone deacetylase inhibitor; DNA topoisomerase (ATP hydrolysing); SUPERCOILED DNA; packaging; HeLa cell line; A-549 cell line; MCF-7 cell line; DNA supercoiling; DNA supercoiling; rat}, year = {2024}, eissn = {1872-8006} } @article{MTMT:34634517, title = {Understanding the structural and functional changes and biochemical pathomechanism of the cardiomyopathy-associated p.R123W mutation in human αB-crystallin}, url = {https://m2.mtmt.hu/api/publication/34634517}, author = {Somee, L.R. and Barati, A. and Shahsavani, M.B. and Hoshino, M. and Hong, J. and Kumar, A. and Moosavi-Movahedi, A.A. and Amanlou, M. and Yousefi, R.}, doi = {10.1016/j.bbagen.2024.130579}, journal-iso = {BBA-GEN SUBJECTS}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS}, volume = {1868}, unique-id = {34634517}, issn = {0304-4165}, year = {2024}, eissn = {1872-8006} } @article{MTMT:34613076, title = {Biosynthesis, characterization, magnetic hyperthermia, and in vitro toxicity evaluation of quercetin-loaded magnetoliposome lipid bilayer hybrid system on MCF-7 breast cancer}, url = {https://m2.mtmt.hu/api/publication/34613076}, author = {Elbeltagi, Shehab and Saeedi, Ahmad M. and Eldin, Zienab E. and Alfassam, Haifa E. and Alharbi, Hanan M. and Madkhali, Nawal and Shakor, Abo Bakr Abdel and Abd El-Aal, Mohamed}, doi = {10.1016/j.bbagen.2023.130543}, journal-iso = {BBA-GEN SUBJECTS}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS}, volume = {1868}, unique-id = {34613076}, issn = {0304-4165}, abstract = {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.}, keywords = {Liposomes; Quercetin; MHT; Chemotherapy/hyperthermia; And MCF-7 breast cancer}, year = {2024}, eissn = {1872-8006} } @article{MTMT:34590294, title = {Nanotechnology in the diagnostic and therapy for Alzheimer's disease}, url = {https://m2.mtmt.hu/api/publication/34590294}, author = {Panghal, Archna and Flora, S. J. S.}, doi = {10.1016/j.bbagen.2024.130559}, journal-iso = {BBA-GEN SUBJECTS}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS}, volume = {1868}, unique-id = {34590294}, issn = {0304-4165}, abstract = {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.}, keywords = {NANOPARTICLES; Alzheimer's disease; Quantum dots; Nanotechnology; Nanomedicine; Amyloid plaques; nanotherapeutics; theragnostic; Nano -diagnostics}, year = {2024}, eissn = {1872-8006} } @article{MTMT:34523181, title = {Advanced nanoscale delivery systems for mRNA-based vaccines}, url = {https://m2.mtmt.hu/api/publication/34523181}, author = {Mobasher, M. and Ansari, R. and Castejon, A.M. and Barar, J. and Omidi, Y.}, doi = {10.1016/j.bbagen.2024.130558}, journal-iso = {BBA-GEN SUBJECTS}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS}, volume = {1868}, unique-id = {34523181}, issn = {0304-4165}, abstract = {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.}, keywords = {NANOPARTICLES; viral and nonviral vectors; mRNA vaccines; Vaccine delivery systems; Self-amplifying RNA (saRNA) vaccines}, year = {2024}, eissn = {1872-8006} } @article{MTMT:34503056, title = {DHX33 mediates p53 to regulate mevalonate pathway gene transcription in human cancers}, url = {https://m2.mtmt.hu/api/publication/34503056}, author = {Nie, G. and Chen, S. and Song, Q. and Zou, D. and Li, M. and Tang, X. and Deng, Y. and Huang, B. and Yang, M. and Lv, G. and Zhang, Y.}, doi = {10.1016/j.bbagen.2023.130547}, journal-iso = {BBA-GEN SUBJECTS}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS}, volume = {1868}, unique-id = {34503056}, issn = {0304-4165}, abstract = {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.}, keywords = {ARTICLE; MOUSE; human; protein analysis; gene expression regulation; gene mutation; controlled study; nonhuman; animal tissue; animal model; animal experiment; animal cell; cell proliferation; in vitro study; embryo; human cell; cholesterol; unclassified drug; protein expression; solid tumor; in vivo study; protein depletion; RAS; lung cancer; protein protein interaction; upregulation; CARCINOGENESIS; transcription regulation; p53; protein p53; oncogene K ras; cholesterol metabolism; null cell; Mevalonate pathway; gene knockdown; mevalonic acid; RNA helicase; RNA helicase; DHX33; protein DHX33}, year = {2024}, eissn = {1872-8006} } @article{MTMT:34621618, title = {Mass spectrometry imaging of metals in tissues and cells: Methods and biological applications}, url = {https://m2.mtmt.hu/api/publication/34621618}, author = {Gorman, Brittney L. and Torti, Suzy V. and Torti, Frank M. and Anderton, Christopher R.}, doi = {10.1016/j.bbagen.2023.130329}, journal-iso = {BBA-GEN SUBJECTS}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS}, volume = {1868}, unique-id = {34621618}, issn = {0304-4165}, keywords = {SIMS; LA-ICP-MS; DESI; MALDI; Metallomics; CyTOF; spatial metabolomics}, year = {2024}, eissn = {1872-8006} } @article{MTMT:34616308, title = {Plant histone variants at the nexus of chromatin readouts, stress and development}, url = {https://m2.mtmt.hu/api/publication/34616308}, author = {Sundar, G. Vivek Hari and Madhu, Aravind and Archana, A. and Shivaprasad, P. V.}, doi = {10.1016/j.bbagen.2023.130539}, journal-iso = {BBA-GEN SUBJECTS}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS}, volume = {1868}, unique-id = {34616308}, issn = {0304-4165}, abstract = {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.}, keywords = {gene regulation; Histone modifications; Histone variants; Plant epigenetics}, year = {2024}, eissn = {1872-8006} } @article{MTMT:34601608, title = {Biomolecular dynamics in the 21st century}, url = {https://m2.mtmt.hu/api/publication/34601608}, author = {Brooks III, Charles L. and MacKerell Jr, Alexander D. and Post, Carol B. and Nilsson, Lennart}, doi = {10.1016/j.bbagen.2023.130534}, journal-iso = {BBA-GEN SUBJECTS}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS}, volume = {1868}, unique-id = {34601608}, issn = {0304-4165}, abstract = {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.}, keywords = {simulation; sampling; force field}, year = {2024}, eissn = {1872-8006} } @article{MTMT:34580245, title = {Structural and functional characterization of triketone dioxygenase from Oryza Sativa}, url = {https://m2.mtmt.hu/api/publication/34580245}, author = {Duff, Stephen M. G. and Zhang, Meiying and Zinnel, Fred and Rydel, Timothy and Taylor, Christina M. and Chen, Danqi and Tilton, Gregory and Mamanella, Patricia and Duda, David and Wang, Yanfei and Xiang, Bosong and Karunanandaa, Balasulojini and Varagona, Rita and Chittoor, Jaishree and Qi, Qungang and Hall, Erin and Garvey, Graeme and Zeng, Jiamin and Zhang, Jun and Li, Xin and White, Tommi and Jerga, Agoston and Haas, Jeff}, doi = {10.1016/j.bbagen.2023.130504}, journal-iso = {BBA-GEN SUBJECTS}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS}, volume = {1868}, unique-id = {34580245}, issn = {0304-4165}, abstract = {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.}, keywords = {herbicide; TRANSGENE; herbicide tolerance; mesotrione; Hydroxyphenylpyruvate dioxygenase; Triketone; iron/2-oxoglutarate-dependent oxidoreductase}, year = {2024}, eissn = {1872-8006} }