Editorial Material
Biology
Na Yang, Payel Sen
Summary: Many senescence-associated features gradually emerge before cells cease to divide.
Article
Biochemistry & Molecular Biology
Emil Mladenov, Katja Paul-Konietzko, Veronika Mladenova, Martin Stuschke, George Iliakis
Summary: Sophisticated mechanisms have evolved in higher eukaryotes to repair DNA double-strand breaks (DSBs) through different repair pathways. These repair pathways not only contribute to DSB repair, but also influence the integration of foreign DNA or rearrangement of genetic information in cells. However, the efficiency of gene targeting is generally low in somatic cells due to random integration of DNA fragments. In contrast, embryonic stem cells and certain lymphoblastic cell lines show increased gene-targeting efficiency.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Angelica Giuliani, Maria Giulia Bacalini, Deborah Ramini, Emanuela Mensa, Chiara Giordani, Luciano Xumerle, Paolo Garagnani, Fabiola Olivieri, Antonio Domenico Procopio, Maria Rita Rippo, Jacopo Sabbatinelli
Summary: Bone marrow mesenchymal stromal cells (BMSCs) have the ability to self-renew and differentiate into adipocytes and osteoblasts, but the role of DNA methylation in their function and replicative senescence is still unclear. A genome-wide DNA methylation analysis revealed genome-wide hypomethylation and overlapping differentially methylated positions (DMPs) in replicative senescent BMSCs and HUVECs. Pathway analysis identified common pathways associated with senescence, insulin resistance, molecule adhesion, and Wnt/beta-catenin signaling. This study provides valuable insights into the mechanisms of replicative senescence and BMSC differentiation.
Article
Biochemistry & Molecular Biology
Benjamin B. Morris, Jason P. Smith, Qi Zhang, Zhijie Jiang, Oliver A. Hampton, Michelle L. Churchman, Susanne M. Arnold, Dwight H. Owen, Jhanelle E. Gray, Patrick M. Dillon, Hatem H. Soliman, Daniel G. Stover, Howard Colman, Arnab Chakravarti, Kenneth H. Shain, Ariosto S. Silva, John L. Villano, Michael A. Vogelbaum, Virginia F. Borges, Wallace L. Akerley, Ryan D. Gentzler, Richard D. Hall, Cindy B. Matsen, C. M. Ulrich, Andrew R. Post, David A. Nix, Eric A. Singer, James M. Larner, Peter Todd Stukenberg, David R. Jones, Marty W. Mayo
Summary: This study identified a new pan-cancer class of tumors, replicative instability (RIN), characterized by intra-chromosomal gene-level gain and loss events at replication stress sensitive genome sites. RIN was found to drive therapy resistance and distant metastases across multiple tumor types, indicating its significant importance in cancer research.
Article
Pharmacology & Pharmacy
Idoia Meaza, Aggie R. Williams, Haiyan Lu, Jennifer H. Toyoda, Tayler J. Croom-Perez, Sandra S. Wise, Abou El-Makarim Aboueissa, John Pierce Wise Sr
Summary: Cr(VI) is a human lung carcinogen that causes DNA double strand breaks and chromosomal instability. Prolonged exposure inhibits repair and leads to chromosome instability in human bronchial epithelial cells.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Rujira Wanotayan, Khaisang Chousangsuntorn, Phasit Petisiwaveth, Thunchanok Anuttra, Waritsara Lertchanyaphan, Tanwiwat Jaikuna, Kulachart Jangpatarapongsa, Pimpon Uttayarat, Teerawat Tongloy, Chousak Chousangsuntorn, Siridech Boonsang
Summary: The study introduced a novel automated foci scoring method using deep learning and a YOLO algorithm for quantifying gamma-H2AX foci in peripheral blood samples, achieving comparable results to manual scoring.
SCIENTIFIC REPORTS
(2022)
Article
Genetics & Heredity
S. Kocher, J. Volquardsen, A. Perugachi Heinsohn, C. Petersen, D. Roggenbuck, K. Rothkamm, W. Y. Mansour
Summary: The article discusses an automated method for quantifying DNA damage-induced foci in adherent tumor cells, ensuring fast and reliable automated nuclei detection through critical steps. The system was validated for IR dose-dependent increase and ATM and PARP inhibitor-induced radiosensitization, providing a cost-effective, high throughput analysis of DNA damage induced foci.
Article
Dentistry, Oral Surgery & Medicine
L. Yao, F. Li, C. Yu, H. Wang, Y. Wang, L. Ye, F. Yu
Summary: The influence of chronological and replicative senescence on CD51(+)/PDGFR-alpha(+) hDPSCs was investigated using various experimental methods. Chronological senescence led to decreased CD51(+)/PDGFR-alpha(+) hDPSCs, impaired self-renewal, and higher ossificatory differentiation. Replicative senescence resulted in decreased CD51 expression, upregulated PDGFR-alpha expression, and weakened self-renewal and osteogenic differentiation. These findings highlight the distinct outcomes and core dysfunction of chronological and replicative senescence in CD51(+)/PDGFR-alpha(+) hDPSCs.
JOURNAL OF DENTAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Shankari Nair, Samantha Cairncross, Xanthene Miles, Monique Engelbrecht, Peter du Plessis, Julie Bolcaen, Randall Fisher, Roya Ndimba, Charnay Cunningham, Wilner Martinez-Lopez, Christian Schunck, Charlot Vandevoorde
Summary: The protocol discusses a method for detecting DNA double strand breaks using fluorescently labeled gamma-H2AX protein and an automated microscopy platform for analysis, showing a fast and sensitive approach for biological dosimetry applications.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2021)
Article
Oncology
Thorsten Derlin, Natalia Bogdanova, Fiona Ohlendorf, Dhanya Ramachandran, Rudolf A. Werner, Tobias L. Ross, Hans Christiansen, Frank M. Bengel, Christoph Henkenberens
Summary: Assessment of gamma-H2AX and 53BP1 foci formation in peripheral blood lymphocytes of patients receiving radioligand therapy may hold promise for predicting early treatment response and subclinical hematotoxicity.
Article
Biology
Judith Mine-Hattab, Mathias Heltberg, Marie Villemeur, Chloe Guedj, Thierry Mora, Aleksandra M. Walczak, Maxime Dahan, Angela Taddei
Summary: In response to double strand breaks, repair proteins accumulate at damaged sites, forming membrane-less sub-compartments or foci. Rad52 molecules freely diffuse within repair foci while Rfa1 molecules bind to ssDNA, suggesting the existence of a liquid droplet structure around damaged DNA.
Article
Biochemistry & Molecular Biology
Arun Mouli Kolinjivadi, Haresh Sankar, Ramveer Choudhary, Lavina Sierra Tay, Tuan Zea Tan, Naoko Murata-Kamiya, Dominic Chih-Cheng Voon, Dennis Kappei, Masanori Hatakeyama, Vaidehi Krishnan, Yoshiaki Ito
Summary: The bacterial pathogen H. pylori exploits the host DNA repair proteins to induce genomic instability by downregulating key DNA repair genes such as FANCI, FANCD2, BRCA1, and BRCA2 through the virulence factor CagA. This results in impaired fork stability, increased DNA double strand breaks, and compromised genome stability, revealing a novel mechanism of bacterial virulence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Erika Casari, Marco Gnugnoli, Carlo Rinaldi, Paolo Pizzul, Chiara Vittoria Colombo, Diego Bonetti, Maria Pia Longhese
Summary: Early research found that telomeres possess the ability to escape fusions and require specific proteins and structural properties for protection. Telomeres shorten with cell division, leading to replicative senescence as a barrier against tumorigenesis. However, downregulation of the checkpoint may result in genomic instability and potentially drive tumorigenesis if telomeres are re-stabilized.
Article
Cell Biology
Andrey Osipov, Anna Chigasova, Elizaveta Yashkina, Maxim Ignatov, Yuriy Fedotov, Daria Molodtsova, Natalia Vorobyeva, Andreyan N. Osipov
Summary: Residual foci of DNA repair observed after irradiation are potential sites for DNA double strand break repair. The changes in their quantitative markers and their role in cell death and senescence processes have not been well studied. In this study, the association between changes in residual foci and key DNA damage response proteins, as well as the proportion of caspase-3 positive, LC-3 II autophagic, and SA-beta-gal senescent cells, was investigated. The results showed that the number of residual foci and caspase-3 positive cells decreased over time, while the proportion of senescent cells increased. The highest number of autophagic cells was observed at 48 hours post-irradiation. Overall, these findings provide important insights into the dose-dependent cellular response in irradiated fibroblasts.
Article
Biochemistry & Molecular Biology
Lucian Zastko, Anna Rackova, Petra Petrovicova, Matus Durdik, Jakub Misek, Eva Markova, Igor Belyaev
Summary: The dephosphorylation inhibitor calyculin A has been shown to have no effect on radiation-induced gamma H2AX foci at low doses, but decreases all types of DNA repair foci induced by 100 cGy irradiation. Calyculin A treatment induces apoptosis in UCBL, potentially leading to the failure to maintain radiation-induced gamma H2AX foci.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Lina Alhaddad, Zain Nofal, Margarita Pustovalova, Andreyan N. Osipov, Sergey Leonov
Summary: The overall effect of senescence on cancer progression and cancer cell resistance to X-ray radiation is still unclear and controversial. This study aimed to investigate the effects of repeated passaging on the biological and functional characteristics of short- and long-term passaging glioblastoma multiforme cells responding to senescence-inducing DNA-damaging IR stress. The results showed that short-term cultured cells displayed premature senescence signs, while long-term cultured cells exhibited increased multinucleated giant cancer cells and higher radiosensitivity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Yan A. Ivanenkov, Daniil Polykovskiy, Dmitry Bezrukov, Bogdan Zagribelnyy, Vladimir Aladinskiy, Petrina Kamya, Alex Aliper, Feng Ren, Alex Zhavoronkov
Summary: Chemistry42 is a software platform that combines Artificial Intelligence techniques with computational and medicinal chemistry methodologies for de novo small molecule design and optimization. It efficiently generates novel molecular structures with optimized properties, which are validated in both in vitro and in vivo studies. Chemistry42 is part of Insilico Medicine's Pharma.ai drug discovery suite, along with PandaOmics for target discovery and multiomics data analysis, and inClinico for data-driven forecast of a clinical trial's probability of success.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Multidisciplinary
Feng Ren, Xiao Ding, Min Zheng, Mikhail Korzinkin, Xin Cai, Wei Zhu, Alexey Mantsyzov, Alex Aliper, Vladimir Aladinskiy, Zhongying Cao, Shanshan Kong, Xi Long, Bonnie Hei Man Liu, Yingtao Liu, Vladimir Naumov, Anastasia Shneyderman, Ivan V. Ozerov, Ju Wang, Frank W. Pun, Daniil A. Polykovskiy, Chong Sun, Michael Levitt, Alan Aspuru-Guzik, Alex Zhavoronkov
Summary: The application of artificial intelligence (AI) in drug discovery has revolutionized the field. The AlphaFold program's ability to predict protein structures for the entire human genome is considered a remarkable breakthrough. By applying AlphaFold, we successfully identified a novel hit molecule for a novel target without experimental structure.
Article
Sport Sciences
Kristina A. A. Malsagova, Tatiana A. A. Astrelina, Evgenii I. I. Balakin, Irina V. V. Kobzeva, Elena Ya. Adoeva, Kseniya A. A. Yurku, Yuliya B. B. Suchkova, Alexander A. A. Stepanov, Alexander A. A. Izotov, Tatyana V. V. Butkova, Anna L. L. Kaysheva, Vasiliy I. I. Pustovoyt
Summary: Neuroplasticity and inflammation are important in the body's adaptive reactions to prolonged physical activity. These processes involve the cross-interaction of the nervous and immune systems through neurotransmitter and cytokine signals. Our study using flow cytometry and advanced biochemical analysis showed that intense and prolonged physical activity without nutritional and metabolic support contributes to exercise-induced immunosuppression in athletes, as indicated by decreased leukocyte count, lowered immunoregulatory index (CD4(+)/CD8(+)), and reduced indicators of humoral immunity (immunoglobulins A, M, G, and IFN-gamma). These findings suggest a reduced immune status and increased susceptibility to exercise-induced immunosuppression in athletes.
Review
Biochemistry & Molecular Biology
Sergey Leonov, Olumide Inyang, Konstantin Achkasov, Elizaveta Bogdan, Elizaveta Kontareva, Yongheng Chen, Ying Fu, Andreyan N. N. Osipov, Margarita Pustovalova, Yulia Merkher
Summary: Metastasis is the leading cause of cancer-related deaths, and predicting its occurrence is crucial for improving survival rates. Current prediction methods, such as lymph-node status and genetic testing, have limitations and may take weeks to obtain results. New mechanobiology-related techniques based on the mechanical invasiveness of cancer cells have shown promise in detecting metastasis propensity. However, they are still complex and require further exploration. Investigating novel markers related to the mechanobiological properties of tumor cells may significantly impact the prognosis of metastasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Environmental Sciences
Dominique Laurier, Yann Billarand, Dmitry Klokov, Klervi Leuraud
Summary: The use of the LNT model in radiation protection is still debated, but recent research in radiobiology and epidemiology has reinforced our scientific understanding of cancer risks at low doses. In radiobiology, early carcinogenic events show linear responses to doses as low as 10 mGy, while epidemiological studies indicate excess cancer risks at dose levels of 100 mGy or less. Overall, the LNT model does not substantially overestimate risks at low doses, and current scientific knowledge does not contradict its use in the radiological protection system.
JOURNAL OF RADIOLOGICAL PROTECTION
(2023)
Article
Biochemistry & Molecular Biology
T. F. Malivanova, T. A. Astrelina, I. V. Kobzeva, V. A. Nikitina, Yu. B. Suchkova, A. S. Ostashkin, D. Yu. Usupzhanova, E. I. Dobrovolskaya, V. A. Brunchukov, A. A. Rastorgueva, E. E. Lomonosova, E. S. Lubaeva, E. Yu. Kretova, N. G. Stepanyants, M. Yu. Sukhova, A. S. Samoilov
Summary: This study assessed the effect of the AH8.1 haplotype on sTNF levels and clinical characteristics in breast cancer patients. It was found that breast cancer patients carrying the AH8.1 haplotype had significantly elevated sTNF levels. Anti-TNF therapy may be considered for breast cancer patients with the -308A/AH8.1- genotype due to their unfavorable prognosis.
MOLECULAR GENETICS MICROBIOLOGY AND VIROLOGY
(2023)
Review
Pharmacology & Pharmacy
Frank W. Pun, Ivan V. Ozerov, Alex Zhavoronkov
Summary: Disease modeling and target identification are crucial in drug discovery, and artificial intelligence is increasingly being used in this field. This article reviews recent advances in AI-driven target discovery and discusses the importance of striking a balance between novelty and confidence in target selection. It also highlights the validation of AI-identified targets through experiments and the potential pathways for further development.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Article
Chemistry, Medicinal
Yan Ivanenkov, Bogdan Zagribelnyy, Alex Malyshev, Sergei Evteev, Victor Terentiev, Petrina Kamya, Dmitry Bezrukov, Alex Aliper, Feng Ren, Alex Zhavoronkov
Summary: This article provides a comprehensive overview of the most recent research outcomes on artificial intelligence-generated molecular structures from the perspective of medicinal chemists. The focus is on studies that involve synthesis, in vitro validation, and analysis of the relevance and novelty of these structures in modern medicinal chemistry. The authors believe that this review will be valuable to the medicinal chemistry and AI-driven drug design communities as a comprehensive approach for evaluating different research outcomes in AIDD.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Health Care Sciences & Services
Irina Kobzeva, Tatiana Astrelina, Yuliya Suchkova, Tatyana Malivanova, Daria Usupzhanova, Vitaliy Brunchukov, Anna Rastorgueva, Victoria Nikitina, Ekaterina Lubaeva, Marina Sukhova, Alexey Kirilchev, Tatyana Butkova, Alexander Izotov, Kristina Malsagova, Alexander Samoilov, Vasiliy Pustovoyt
Summary: This study investigated the effect of radiation therapy on the composition of lymphocyte populations in patients with breast cancer. The findings showed a significant reduction in B cells, T cells, and natural killer cells after radiation therapy. These changes are important for clinical management and the use of targeted therapy or immunotherapy.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Margarita Pustovalova, Philipp Malakhov, Anastasia Guryanova, Maxim Sorokin, Maria Suntsova, Anton Buzdin, Andreyan N. N. Osipov, Sergey Leonov
Summary: Radioresistance is a major obstacle in the successful therapy of many cancers, including non-small cell lung cancer (NSCLC). By comparing the transcriptional changes of radioresistant NSCLC cells with parental cells using RNA-seq, differentially expressed genes associated with radioresistance were identified. These gene expressions reflect the complex biological processes involved in clinical cancer cell eradication and might serve as potential biomarkers and therapeutic targets for NSCLC treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Lina Alhaddad, Roman Chuprov-Netochin, Margarita Pustovalova, Andreyan N. Osipov, Sergey Leonov
Summary: The relationship between radiation tolerance and the formation of polyploid/multinucleated giant (PGCC/MGCC) and quiescent/senescent cancer cells in glioblastoma multiforme (GBM) cell lines was investigated. The study revealed an increase in MGCC populations and the development of Raju cells in response to X-ray irradiation in U-87 and LN-229 cell lines. Single-cell imaging showed that radiation exposure augmented two distinct GBM cell populations, with one resembling PGCC/MGCCs, indicating high radioresistance. Proliferative activity and survival of GBM cell lines were found to be related to neosis and specific gene expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Oleg Belov, Anna Chigasova, Margarita Pustovalova, Andrey Osipov, Petr Eremin, Natalia Vorobyeva, Andreyan N. Osipov
Summary: This study presents experimental evidence and quantitative modeling analysis showing that increased radiation dose leads to a decrease in the relative contribution of homologous recombination in the DNA repair process.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Daria Molodtsova, Denis V. Guryev, Andreyan N. Osipov
Summary: Resistance to chemotherapy or radiotherapy is a major challenge in the treatment of oncology patients. This review focuses on the secretory factors from resistant cancer cells, cancer-associated fibroblasts, mesenchymal stem cells, and cancer stem cells that contribute to the development of resistance in non-exposed cells. The study highlights the potential diagnostic significance of these factors in intercellular fluid and blood.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
