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Dutta D, Chatterjee N. Expanding scope of genetic studies in the era of biobanks. Hum Mol Genet 2025:ddaf054. [PMID: 40312842 DOI: 10.1093/hmg/ddaf054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Revised: 03/25/2025] [Accepted: 04/08/2025] [Indexed: 05/03/2025] Open
Abstract
Biobanks have become pivotal in genetic research, particularly through genome-wide association studies (GWAS), driving transformative insights into the genetic basis of complex diseases and traits through the integration of genetic data with phenotypic, environmental, family history, and behavioral information. This review explores the distinct design and utility of different biobanks, highlighting their unique contributions to genetic research. We further discuss the utility and methodological advances in combining data from disease-specific study or consortia with that of biobanks, especially focusing on summary statistics based meta-analysis. Subsequently we review the spectrum of additional advantages offered by biobanks in genetic studies in representing population differences, calibration of polygenic scores, assessment of pleiotropy and improving post-GWAS in silico analyses. Advances in sequencing technologies, particularly whole-exome and whole-genome sequencing, have further enabled the discovery of rare variants at biobank scale. Among recent developments, the integration of large-scale multi-omics data especially proteomics and metabolomics, within biobanks provides deeper insights into disease mechanisms and regulatory pathways. Despite challenges like ascertainment strategies and phenotypic misclassification, biobanks continue to evolve, driving methodological innovation and enabling precision medicine. We highlight the contributions of biobanks to genetic research, their growing integration with multi-omics, and finally discuss their future potential for advancing healthcare and therapeutic development.
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Affiliation(s)
- Diptavo Dutta
- Integrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD, 20879, United States
| | - Nilanjan Chatterjee
- Department of Biostatistics, Johns Hopkins University, 615 N Wolfe Street, Baltimore, MD, 21205, United States
- Department of Oncology, Johns Hopkins University, 615 N Wolfe Street, Baltimore, MD, 21205, United States
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Mohanty A, Srinivasan A, Udupaa P, Catchpoole D. Multiomics and tumor banking: comprehensive plaforms- integrating cancer diversity, biomarker discovery and personalised cancer care in India. Hum Mol Genet 2025:ddaf033. [PMID: 40287834 DOI: 10.1093/hmg/ddaf033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 01/24/2025] [Accepted: 02/25/2025] [Indexed: 04/29/2025] Open
Abstract
Biobanks are innovative biomedical research infrastructures that play a crucial role in advancing cancer research by supporting investigations into the etiology, progression, and therapeutic interventions of the disease. Biobanks have significantly contributed to personalized medicine by providing high-quality bio specimen resources and expertise in tissue handling, essential for understanding the interplay of genetic, ecological, and lifestyle factors on cancer biology, human health, and mortality. By linking bio specimens with clinical, pathological, and epidemiological data, biobanks are central in the discovery and development of cancer therapeutics through biomarkers. In this review, the importance of managing biobanks as integral parts of data generation and analytics continuum driving precision medicine is pointed out. The advent of multi-OMICS analytics, combined with artificial intelligence, systems biology, and deep machine learning, has elevated the importance of bio banking human bio specimens as not only a biological resource but also an informatics asset. Here, we examine the impact of bio banking in facilitating translational, bench-to-bedside cancer research, with a focus on multi-OMICS data-driven biomarker discovery and precision oncology. In addition, we discuss one of the major innovations in biobank management: the hub-and-spoke model. This centralized system leverages core expertise and resources while collecting bio specimens from diverse geographic regions, thereby capturing the heterogeneity of cancer biology. The hub-and-spoke approach is particularly advantageous for countries like India, characterized by vast geographic and demographic diversity. It ensures complete coverage of the different types of cancers, disease stages, and population groups in addressing the complexity and diversity of cancer biology.
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Affiliation(s)
- Abhishek Mohanty
- HCG Centre for Biorepository and Biobanking, Health Care Global (HCG) Cancer Hospitals, HCG Towers, #8, P. Kalinga Rao Road,Sampangi Ram Nagar, Bangalore 560027, India
| | - Apoorva Srinivasan
- HCG Centre for Biorepository and Biobanking, Health Care Global (HCG) Cancer Hospitals, HCG Towers, #8, P. Kalinga Rao Road,Sampangi Ram Nagar, Bangalore 560027, India
| | - Pallavi Udupaa
- S-DACC Healthcare Pvt Ltd, 1872, 11th A Main Rd, 4th T Block East, Pattabhirama Nagar, Jayanagar, Bengaluru, Karnataka 560041, India
| | - Daniel Catchpoole
- The Kids Research Institute, The Children's Hospital, Westmead Locked Bag 4001 Westmead, NSW, 2145, Australia
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Jin Y, Yoon HJ, Park KW, Lee H, Tan Y, Ryu BJ, Lee SM, Cho CE, Kim JG, Kim NA, Park YM. Effects of Vitamin E Intake and Voluntary Wheel Running on Whole-Body and Skeletal Muscle Metabolism in Ovariectomized Mice. Nutrients 2025; 17:991. [PMID: 40290065 PMCID: PMC11944365 DOI: 10.3390/nu17060991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2025] [Revised: 03/09/2025] [Accepted: 03/10/2025] [Indexed: 04/30/2025] Open
Abstract
Background/Objectives: Ovariectomized rodents experience metabolic dysfunction in whole-body and skeletal muscle. A disrupted balance between oxidative stress and antioxidants might exacerbate metabolic dysfunction in ovariectomized rodents. Dietary antioxidants, such as vitamin E intake, before or during exercise would be beneficial by mitigating the exercise-induced increase in oxidative stress in ovariectomized rodents. The purpose of the current study was to investigate the potential effect of vitamin E intake combined with voluntary exercise on whole-body and skeletal muscle metabolism in ovariectomized mice. Methods: This study used C57BL/6J wild-type female mice (n = 40, 8 weeks old), which were randomly assigned into sham (SHM), ovariectomy (OVX), ovariectomy with exercise (OVXVE), ovariectomy with vitamin E (OVXV), ovariectomy with exercise and vitamin E (OVXVE) groups. Body composition, resting metabolic rate, glucose tolerance, skeletal muscle mitochondrial function, and protein contents were assessed using dual-energy x-ray absorptiometry, indirect calorimetry, glucose tolerance test, O2K OROBOROS, and Western blot, respectively. Results: The combined treatment of vitamin E and voluntary wheel running did not show a beneficial effect on whole-body metabolism such as fat mass, energy expenditure, and glucose tolerance. However, independent of exercise intervention, vitamin E intake enhanced mitochondrial function, Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1-a), and adenosine monophosphate-activated protein kinase (AMPK) levels and also reduced oxidative stress in the skeletal muscles of ovariectomized mice. Specifically, in the soleus muscle, vitamin E intake enhanced mitochondrial function and PGC1-a content (p < 0.05). In the gastrocnemius muscle, vitamin E intake enhanced PGC1-a and AMPK levels and reduced a marker of oxidative stress (p < 0.05). Conclusions: Vitamin E, as a potent antioxidant, may play a crucial role in maintaining skeletal muscle health in ovariectomized mice. More studies are necessary to investigate whether this finding is applicable to women.
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Affiliation(s)
- Youngyun Jin
- College of Sport Science, Sungkyunkwan University, Suwon 16419, Republic of Korea;
| | - Hee-Jung Yoon
- Division of Health and Kinesiology, Incheon National University, Incheon 22012, Republic of Korea; (H.-J.Y.); (K.-W.P.); (H.L.); (Y.T.); (B.-J.R.); (S.-M.L.); (C.-E.C.)
| | - Ki-Woong Park
- Division of Health and Kinesiology, Incheon National University, Incheon 22012, Republic of Korea; (H.-J.Y.); (K.-W.P.); (H.L.); (Y.T.); (B.-J.R.); (S.-M.L.); (C.-E.C.)
| | - Hanall Lee
- Division of Health and Kinesiology, Incheon National University, Incheon 22012, Republic of Korea; (H.-J.Y.); (K.-W.P.); (H.L.); (Y.T.); (B.-J.R.); (S.-M.L.); (C.-E.C.)
- Sport Science Institute & Health Promotion Center, Incheon National University, Incheon 22012, Republic of Korea
| | - Yuan Tan
- Division of Health and Kinesiology, Incheon National University, Incheon 22012, Republic of Korea; (H.-J.Y.); (K.-W.P.); (H.L.); (Y.T.); (B.-J.R.); (S.-M.L.); (C.-E.C.)
| | - Byung-Jun Ryu
- Division of Health and Kinesiology, Incheon National University, Incheon 22012, Republic of Korea; (H.-J.Y.); (K.-W.P.); (H.L.); (Y.T.); (B.-J.R.); (S.-M.L.); (C.-E.C.)
| | - Seung-Min Lee
- Division of Health and Kinesiology, Incheon National University, Incheon 22012, Republic of Korea; (H.-J.Y.); (K.-W.P.); (H.L.); (Y.T.); (B.-J.R.); (S.-M.L.); (C.-E.C.)
| | - Chae-Eun Cho
- Division of Health and Kinesiology, Incheon National University, Incheon 22012, Republic of Korea; (H.-J.Y.); (K.-W.P.); (H.L.); (Y.T.); (B.-J.R.); (S.-M.L.); (C.-E.C.)
| | - Jae-Geun Kim
- Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of Korea;
| | - Nam-Ah Kim
- Department of Pharmacy, College of Pharmacy, Mokpo National University, Muan 58554, Republic of Korea
- Department of Biomedicine, Health & Life Convergence Sciences, BK21 Four, Biomedical and Healthcare Research Institute, Mokpo National University, Muan 58554, Republic of Korea
| | - Young-Min Park
- Division of Health and Kinesiology, Incheon National University, Incheon 22012, Republic of Korea; (H.-J.Y.); (K.-W.P.); (H.L.); (Y.T.); (B.-J.R.); (S.-M.L.); (C.-E.C.)
- Sport Science Institute & Health Promotion Center, Incheon National University, Incheon 22012, Republic of Korea
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Miyahara R, Taniguchi Y. Synthesis of Oligodeoxynucleotide Containing Pseudo-Deoxycytidine and Its Triphosphate Derivative. Curr Protoc 2025; 5:e70101. [PMID: 40095763 PMCID: PMC11912953 DOI: 10.1002/cpz1.70101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2025]
Abstract
This article describes a detailed synthetic protocol for the preparation of oligodeoxynucleotide (ODN) containing pseudo-deoxycytidine (ψdC) and its triphosphate derivative (ψdCTP). These molecules were synthesized as novel compounds that recognize iso-2'-deoxyguanosine (iso-dG) in DNA. Iso-dG is one of the tautomers of 2-hydroxy-2'-deoxyadenosine (2-OH-dA), which is known as an oxidatively damaged nucleobase, and its selective recognition in DNA is expected to play a very important role in the diagnosis and pathogenesis of diseases. The hydroxyl groups of the known glycal compound were protected with silyl groups, and then coupled with 5-iodouracil under Mizorogi-Heck reaction conditions, yielding ψdU after desilylation and diastereoselective reduction. The endocyclic amino group of ψdU was protected by the benzyl group. Subsequently, the carbonyl group at the 6-position of the nucleobase was activated and converted to an amino group through treatment with aqueous ammonia. The benzyl group was removed, and the exocyclic amino group was protected with a benzoyl group. On one hand, the silyl groups at the 3' and 5' positions were deprotected, converted into a phosphoramidite unit, and incorporated into an ODN. On the other hand, the hydroxyl group at the 5' position was selectively deprotected and then directly converted into the triphosphate using Van Boom's reagent under acidic conditions. © 2025 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Synthesis of ODNs having ψdC and ψdCTP Basic Protocol 2: Melting temperature of duplex formation between ODNs containing ψdC unit and 2-OH-dA Basic Protocol 3: A single nucleotide primer extension reaction of ψdCTP for a template strand containing 2-OH-dA.
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Affiliation(s)
- Ryo Miyahara
- Graduate School of Pharmaceutical SciencesKyushu UniversityFukuokaJapan
| | - Yosuke Taniguchi
- Faculty of Medicine, Dentistry and Pharmaceutical SciencesOkayama UniversityOkayamaJapan
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Sjöbom U, Isaksson J, Wickelgren R, Vallin L, Nilsson AK, Hellström A, Sävman K, Löfqvist C. Ethical Biobanking in Extremely Preterm Infants: Lessons From the EPITOP Study. Acta Paediatr 2025. [PMID: 39976157 DOI: 10.1111/apa.70035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 01/20/2025] [Accepted: 02/10/2025] [Indexed: 02/21/2025]
Abstract
AIM The Extremely Preterm Infant Target Optimise and Prevent (EPITOP) study aimed to develop an ethical and practical approach to biobanking salvaged residual blood samples from extremely preterm infants (< 28 weeks gestational age, GA) for biomarker research while minimising clinical risks and addressing ethical concerns. METHODS Initiated in collaboration with Sahlgrenska University Hospital and Biobank Väst, Region Västra Götaland, Sweden, residual blood samples were collected from infants admitted to the neonatal intensive care unit (NICU) from March 2020 to March 2024. Samples were ethically salvaged and biobanked following parental consent and in compliance with Sweden's Biobank Act. RESULTS Among 215 eligible infants (mean (GA) 25.4 weeks), 122 consents enabled the collection of 4238 residual samples, of which 92.5% were from blood gas analyses. Sample collection was highest during the first weeks of life, with a median of 35 samples per infant. A higher number of morbidities and lower GA were both associated with an increase in sample numbers. Plasma and whole blood aliquots were prepared and stored for future biomarker studies. CONCLUSION The EPITOP study demonstrates the feasibility of ethically biobanking salvaged residual blood samples from extremely preterm infants. This approach minimises clinical risks while supporting biomarker discovery, providing a scalable model for neonatal research.
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Affiliation(s)
- Ulrika Sjöbom
- Institute of Health and Care Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Jenny Isaksson
- Region Västra Götaland, Biobank Väst, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Ruth Wickelgren
- Region Västra Götaland, Department of Laboratory Medicine, Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden
- Region Norrbotten, Department of Laboratory Medicine, Sunderby Hospital, Södra Sunderbyn, Sweden
| | - Liv Vallin
- Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Region Västra Götaland, Department of Neonatology, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Anders K Nilsson
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Ann Hellström
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Karin Sävman
- Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Region Västra Götaland, Department of Neonatology, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Chatarina Löfqvist
- Institute of Health and Care Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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Colwill M, Baillie S, Pollok R, Poullis A. Biobanks and biomarkers: Their current and future role in biomedical research. World J Methodol 2024; 14:91387. [PMID: 39712565 PMCID: PMC11287535 DOI: 10.5662/wjm.v14.i4.91387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 05/27/2024] [Accepted: 06/11/2024] [Indexed: 07/26/2024] Open
Abstract
The importance and utility of biobanks has increased exponentially since their inception and creation. Initially used as part of translational research, they now contribute over 40% of data for all cancer research papers in the United States of America and play a crucial role in all aspects of healthcare. Multiple classification systems exist but a simplified approach is to either classify as population-based or disease-oriented entities. Whilst historically publicly funded institutions, there has been a significant increase in industry funded entities across the world which has changed the dynamic of biobanks offering new possibilities but also new challenges. Biobanks face legal questions over data sharing and intellectual property as well as ethical and sustainability questions particularly as the world attempts to move to a low-carbon economy. International collaboration is required to address some of these challenges but this in itself is fraught with complexity and difficulty. This review will examine the current utility of biobanks in the modern healthcare setting as well as the current and future challenges these vital institutions face.
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Affiliation(s)
- Michael Colwill
- Department of Gastroenterology, St George's University Hospital NHS Foundation Trust, London SW17 0QT, United Kingdom
| | - Samantha Baillie
- Department of Gastroenterology, St George's University Hospital NHS Foundation Trust, London SW17 0QT, United Kingdom
| | - Richard Pollok
- Department of Gastroenterology, St George's University Hospital NHS Foundation Trust, London SW17 0QT, United Kingdom
| | - Andrew Poullis
- Department of Gastroenterology, St George's University Hospital NHS Foundation Trust, London SW17 0QT, United Kingdom
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Ishiniwa H, Okano T, Endoh D, Hirayama H, Yoshioka A, Yokohata Y, Shindo J, Koshimoto C, Shinohara A, Sakamoto SH, Tamaoki M, Onuma M. Oxidative stress on the male reproductive organs of wild mice collected from an area contaminated by radioactive materials in Fukushima. Sci Rep 2024; 14:29706. [PMID: 39613832 DOI: 10.1038/s41598-024-80869-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Accepted: 11/22/2024] [Indexed: 12/01/2024] Open
Abstract
The Fukushima Daiichi Nuclear Power Plant accident caused the release of large amounts of radioactive material into the environment. Radiation from radionuclides cause DNA lesions, mainly via oxidation, which adversely affect wild organisms by damaging their germ cells. Here, we investigated the effects of radiation on the reproductive organs of Japanese field mice (Apodemus speciosus) by estimating the dose rate of radiation exposure, the accumulation of DNA lesions, and the expression of DNA repair enzymes. In highly contaminated areas, mouse testes received a radiation dose rate > 0.1 mGy/d. According to the International Commission on Radiological Protection, there is a very low probability of effects in the reference rat species at this exposure level. The results of the current study do not definitively conclude that the expression of 8-oxoguanine DNA glycosylase 1 and superoxide dismutase in mouse testes increase with dose rate and lifetime dose. However, 8-hydroxy-2'-deoxyguanosine accumulation increases in a dose rate- and lifetime dose-dependent manner in mouse testes, but is not observed in the sperm of the cauda epididymis. These results suggest that, although DNA lesions occurred in male germ cells of Fukushima mice, most were successfully repaired by DNA repair enzymes at the observed gene expression level.
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Affiliation(s)
- Hiroko Ishiniwa
- Ecological Risk Assessment and Control Section, Center for Environmental Biology and Ecosystem Studies, National Institute for Environmental Studies, 16-2, Onogawa, Tsukuba, Ibaraki, 305-8506, Japan
- Radioecologcial Transfer and Effects Division, Institute of Environmental Radioactivity, Fukushima University, 1 Kanayagawa, Fukushima, Fukushima, 960-1296, Japan
| | - Tsukasa Okano
- Ecological Genetics Analysis Section, Center for Environmental Biology and Ecosystem Studies, National Institute for Environmental Studies, 16-2, Onogawa, Tsukuba, Ibaraki, 305-8506, Japan
| | - Daiji Endoh
- Department of Radiation Biology, School of Veterinary Medicine, Rakuno Gakuen University, 582, Bunkyodai-Midorimachi, Ebetsu, Hokkaido, 069-8501, Japan
| | - Hideo Hirayama
- High Energy Accelerator Research Organization, 1-1, Oho, Tsukuba, Ibaraki, 305-0801, Japan
| | - Akira Yoshioka
- Environmental Impact Assessment Section, Fukushima Regional Collaborative Research Center, National Institute for Environmental Studies, 10-2, Fukasaku, Miharu, Fukushima, 963-7700, Japan
| | - Yasushi Yokohata
- Faculty of Science, Academic Assembly, University of Toyama, Gofuku 3190, Toyama, Toyama, 930-8555, Japan
| | - Junji Shindo
- Laboratory of Wildlife Science, School of Veterinary Medicine, Kitasato University, 23-35-1, Higashi, Towada, Aomori, 034-8628, Japan
| | - Chihiro Koshimoto
- Division of Bio-Resources, Department of Biotechnology, Frontier Science Research Center, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki, 889-1692, Japan
| | - Akio Shinohara
- Division of Bio-Resources, Department of Biotechnology, Frontier Science Research Center, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki, 889-1692, Japan
| | - Shinsuke H Sakamoto
- Division of Bio-Resources, Department of Biotechnology, Frontier Science Research Center, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki, 889-1692, Japan
- Department of Animal and Grassland Sciences, Faculty of Agriculture, University of Miyazaki, Gakuen-kibanadai-nishi-1-1, Miyazaki, 889-2192, Japan
| | - Masanori Tamaoki
- Biodiversity Division, National Institute for Environmental Studies, 16-2, Onogawa, Tsukuba, Ibaraki, 305-8506, Japan
| | - Manabu Onuma
- Ecological Risk Assessment and Control Section, Center for Environmental Biology and Ecosystem Studies, National Institute for Environmental Studies, 16-2, Onogawa, Tsukuba, Ibaraki, 305-8506, Japan.
- Biodiversity Division, National Institute for Environmental Studies, 16-2, Onogawa, Tsukuba, Ibaraki, 305-8506, Japan.
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Capasso E, Casella C, Marisei M, Tortora M, Briganti F, Di Lorenzo P. Imaging biobanks: operational limits, medical-legal and ethical reflections. Front Digit Health 2024; 6:1408619. [PMID: 39268200 PMCID: PMC11391398 DOI: 10.3389/fdgth.2024.1408619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 08/05/2024] [Indexed: 09/15/2024] Open
Abstract
The extraordinary growth of health technologies has determined an increasing interest in biobanks that represent a unique wealth for research, experimentation, and validation of new therapies. "Human" biobanks are repositories of various types of human biological samples. Through years the paradigm has shifted from spontaneous collections of biological material all over the world to institutional, organized, and well-structured forms. Imaging biobanks represent a novel field and are defined by European Society of Radiology as: "organized databases of medical images, and associated imaging biomarkers shared among multiple researchers, linked to other biorepositories". Modern radiology and nuclear medicine can provide multiple imaging biomarkers, that express the phenotype related to certain diseases, especially in oncology. Imaging biobanks, not a mere catalogue of bioimages associated to clinical data, involve advanced computer technologies to implement the emergent field of radiomics and radiogenomics. Since Europe hosts most of the biobanks, juridical and ethical framework, with a specific referral to Italy, is analyzed. Linking imaging biobanks to traditional ones appears to be a crucial step that needs to be driven by medical imaging community under clear juridical and ethical guidelines.
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Affiliation(s)
- Emanuele Capasso
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Claudia Casella
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Mariagrazia Marisei
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Mario Tortora
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Francesco Briganti
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Pierpaolo Di Lorenzo
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
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Heo HS, Kim YE, Lee JH. Antioxidant activity of Jeju lava seawater through translocation of Nrf2 in human fibroblast. Food Sci Biotechnol 2024; 33:2653-2661. [PMID: 39144193 PMCID: PMC11319678 DOI: 10.1007/s10068-023-01510-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 11/20/2023] [Accepted: 12/17/2023] [Indexed: 08/16/2024] Open
Abstract
Reactive oxygen species (ROS) are associated with various pathological conditions, including atherosclerosis and cancer. Photoaging, mainly caused by UVB-induced ROS, accelerates skin aging and collagen degradation. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates antioxidant enzymes and has demonstrated protective effects against chronic diseases. Jeju lava seawater (JLS), which is rich in minerals, is attracting attention for its health benefits. The current study investigates the antioxidant properties of JLS in human dermal fibroblasts (HDFs). experiments were conducted by culturing HDFs in JLS with different water hardness levels and irradiating UVB. The results show that JLS does not affect HDF viability, especially at high water hardness. JLS treatment enhances collagen production and upregulates Nrf2 and antioxidant enzymes such as NQO1 and HO-1. This mechanism involves the translocation of Nrf2 to the cell nucleus. JLS shows promise as an antioxidant, potentially mitigating the effects of oxidative stress and promoting collagen synthesis.
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Affiliation(s)
- Hee Sun Heo
- Department of Food Science and Biotechnology, College of Life Sciences, CHA University, Gyeonggi-do, 11160 Republic of Korea
| | | | - Jong Hun Lee
- Department of Food Science and Biotechnology, College of Bio-Nano Technology, Gachon University, Gyeonggi-do, 13120 Republic of Korea
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Adegbola PI, Adetutu A. Genetic and epigenetic modulations in toxicity: The two-sided roles of heavy metals and polycyclic aromatic hydrocarbons from the environment. Toxicol Rep 2024; 12:502-519. [PMID: 38774476 PMCID: PMC11106787 DOI: 10.1016/j.toxrep.2024.04.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 04/27/2024] [Accepted: 04/27/2024] [Indexed: 05/24/2024] Open
Abstract
This study emphasizes the importance of considering the metabolic and toxicity mechanisms of environmental concern chemicals in real-life exposure scenarios. Furthermore, environmental chemicals may require metabolic activation to become toxic, and competition for binding sites on receptors can affect the severity of toxicity. The multicomplex process of chemical toxicity is reflected in the activation of multiple pathways during toxicity of which AhR activation is major. Real-life exposure to a mixture of concern chemicals is common, and the composition of these chemicals determines the severity of toxicity. Nutritional essential elements can mitigate the toxicity of toxic heavy metals, while the types and ratio of composition of PAH can either increase or decrease toxicity. The epigenetic mechanisms of heavy metals and PAH toxicity involves either down-regulation or up-regulation of some non-coding RNAs (ncRNAs) whereas specific small RNAs (sRNAs) may have dual role depending on the tissue and circumstance of expression. Similarly, decrease DNA methylation and histone modification are major players in heavy metals and PAH mediated toxicity and FLT1 hypermethylation is a major process in PAH induced carcinogenesis. Overall, this review provides the understanding of the metabolism of environmental concern chemicals, emphasizing the importance of considering mixed compositions and real-life exposure scenarios in assessing their potential effects on human health and diseases development as well as the dual mechanism of toxicity via genetic or epigenetic axis.
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Affiliation(s)
- Peter Ifeoluwa Adegbola
- Department of Biochemistry and Forensic Science, First Technical University, Ibadan, Nigeria
| | - Adewale Adetutu
- Department of Biochemistry, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
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Hahm JH, Nirmala FS, Ha TY, Ahn J. Nutritional approaches targeting mitochondria for the prevention of sarcopenia. Nutr Rev 2024; 82:676-694. [PMID: 37475189 DOI: 10.1093/nutrit/nuad084] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/22/2023] Open
Abstract
A decline in function and loss of mass, a condition known as sarcopenia, is observed in the skeletal muscles with aging. Sarcopenia has a negative effect on the quality of life of elderly. Individuals with sarcopenia are at particular risk for adverse outcomes, such as reduced mobility, fall-related injuries, and type 2 diabetes mellitus. Although the pathogenesis of sarcopenia is multifaceted, mitochondrial dysfunction is regarded as a major contributor for muscle aging. Hence, the development of preventive and therapeutic strategies to improve mitochondrial function during aging is imperative for sarcopenia treatment. However, effective and specific drugs that can be used for the treatment are not yet approved. Instead studies on the relationship between food intake and muscle aging have suggested that nutritional intake or dietary control could be an alternative approach for the amelioration of muscle aging. This narrative review approaches various nutritional components and diets as a treatment for sarcopenia by modulating mitochondrial homeostasis and improving mitochondria. Age-related changes in mitochondrial function and the molecular mechanisms that help improve mitochondrial homeostasis are discussed, and the nutritional components and diet that modulate these molecular mechanisms are addressed.
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Affiliation(s)
- Jeong-Hoon Hahm
- Research Group of Aging and Metabolism, Korea Food Research Institute, Wanju-gun, South Korea
| | - Farida S Nirmala
- Research Group of Aging and Metabolism, Korea Food Research Institute, Wanju-gun, South Korea
- Department of Food Biotechnology, Korea University of Science and Technology, Daejeon-si, South Korea
| | - Tae Youl Ha
- Research Group of Aging and Metabolism, Korea Food Research Institute, Wanju-gun, South Korea
- Department of Food Biotechnology, Korea University of Science and Technology, Daejeon-si, South Korea
| | - Jiyun Ahn
- Research Group of Aging and Metabolism, Korea Food Research Institute, Wanju-gun, South Korea
- Department of Food Biotechnology, Korea University of Science and Technology, Daejeon-si, South Korea
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12
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Choi S, Rahman RT, Kim BM, Kang J, Kim J, Shim J, Nam YS. Photochemically Inert Broad-Spectrum Sunscreen by Metal-Phenolic Network Coatings of Titanium Oxide Nanoparticles. ACS APPLIED MATERIALS & INTERFACES 2024; 16:16767-16777. [PMID: 38512769 DOI: 10.1021/acsami.4c00174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/23/2024]
Abstract
Titanium dioxide (TiO2) nanoparticles are extensively used as a sunscreen filter due to their long-active ultraviolet (UV)-blocking performance. However, their practical use is being challenged by high photochemical activities and limited absorption spectrum. Current solutions include the coating of TiO2 with synthetic polymers and formulating a sunscreen product with additional organic UV filters. Unfortunately, these approaches are no longer considered effective because of recent environmental and public health issues. Herein, TiO2-metal-phenolic network hybrid nanoparticles (TiO2-MPN NPs) are developed as the sole active ingredient for sunscreen products through photochemical suppression and absorption spectrum widening. The MPNs are generated by the complexation of tannic acid with multivalent metal ions, forming a robust coating shell. The TiO2-MPN hybridization extends the absorption region to the high-energy-visible (HEV) light range via a new ligand-to-metal charge transfer photoexcitation pathway, boosting both the sun protection factor and ultraviolet-A protection factor about 4-fold. The TiO2-MPN NPs suppressed the photoinduced reactive oxygen species by 99.9% for 6 h under simulated solar irradiation. Accordingly, they substantially alleviated UV- and HEV-induced cytotoxicity of fibroblasts. This work outlines a new tactic for the eco-friendly and biocompatible design of sunscreen agents by selectively inhibiting the photocatalytic activities of semiconductor nanoparticles while broadening their optical spectrum.
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Affiliation(s)
- Saehan Choi
- Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
| | - Rafia Tasnim Rahman
- Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
| | - Bo-Min Kim
- Department of Applied Chemistry, Dongduk Women's University, Seoul 02748, Republic of Korea
| | - Juyeon Kang
- Department of Applied Chemistry, Dongduk Women's University, Seoul 02748, Republic of Korea
| | - Jeonga Kim
- Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
| | - Jongwon Shim
- Department of Applied Chemistry, Dongduk Women's University, Seoul 02748, Republic of Korea
| | - Yoon Sung Nam
- Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
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13
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Najeeb HA, Sanusi T, Saldanha G, Brown K, Cooke MS, Jones GD. Redox modulation of oxidatively-induced DNA damage by ascorbate enhances both in vitro and ex-vivo DNA damage formation and cell death in melanoma cells. Free Radic Biol Med 2024; 213:309-321. [PMID: 38262545 DOI: 10.1016/j.freeradbiomed.2024.01.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 01/10/2024] [Accepted: 01/14/2024] [Indexed: 01/25/2024]
Abstract
Elevated genomic instability in cancer cells suggests a possible model-scenario for their selective killing via the therapeutic delivery of well-defined levels of further DNA damage. To examine this scenario, this study investigated the potential for redox modulation of oxidatively-induced DNA damage by ascorbate in malignant melanoma (MM) cancer cells, to selectively enhance both DNA damage and MM cell killing. DNA damage was assessed by Comet and ɣH2AX assays, intracellular oxidising species by dichlorofluorescein fluorescence, a key antioxidant enzymatic defence by assessment of catalase activity and cell survival was determined by clonogenic assay. Comet revealed that MM cells had higher endogenous DNA damage levels than normal keratinocytes (HaCaT cells); this correlated MM cells having higher intracellular oxidising species and lower catalase activity, and ranked with MM cell melanin pigmentation. Comet also showed MM cells more sensitive towards the DNA damaging effects of exogenous H2O2, and that ascorbate further enhanced this H2O2-induced damage in MM cells; again, with MM cell sensitivity to induced damage ranking with degree of cell pigmentation. Furthermore, cell survival data indicated that ascorbate enhanced H2O2-induced clonogenic cell death selectively in MM cells whilst protecting HaCaT cells. Finally, we show that ascorbate serves to enhance the oxidising effects of the MM therapeutic drug Elesclomol in both established MM cells in vitro and primary cell cultures ex vivo. Together, these results suggest that ascorbate selectively enhances DNA damage and cell-killing in MM cells. This raises the option of incorporating ascorbate into clinical oxidative therapies to treat MM.
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Affiliation(s)
- Hishyar A Najeeb
- Leicester Cancer Research Centre, Department of Genetics & Genome Biology, University of Leicester, UK
| | - Timi Sanusi
- Leicester Medical School, University of Leicester, UK
| | - Gerald Saldanha
- University Hospitals of Leicester NHS Trust, Leicester Royal Infirmary, UK
| | - Karen Brown
- Leicester Cancer Research Centre, Department of Genetics & Genome Biology, University of Leicester, UK
| | - Marcus S Cooke
- Oxidative Stress Group, Department of Molecular Biosciences, University of South Florida, USA.
| | - George Dd Jones
- Leicester Cancer Research Centre, Department of Genetics & Genome Biology, University of Leicester, UK.
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14
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Brancato V, Esposito G, Coppola L, Cavaliere C, Mirabelli P, Scapicchio C, Borgheresi R, Neri E, Salvatore M, Aiello M. Standardizing digital biobanks: integrating imaging, genomic, and clinical data for precision medicine. J Transl Med 2024; 22:136. [PMID: 38317237 PMCID: PMC10845786 DOI: 10.1186/s12967-024-04891-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 01/14/2024] [Indexed: 02/07/2024] Open
Abstract
Advancements in data acquisition and computational methods are generating a large amount of heterogeneous biomedical data from diagnostic domains such as clinical imaging, pathology, and next-generation sequencing (NGS), which help characterize individual differences in patients. However, this information needs to be available and suitable to promote and support scientific research and technological development, supporting the effective adoption of the precision medicine approach in clinical practice. Digital biobanks can catalyze this process, facilitating the sharing of curated and standardized imaging data, clinical, pathological and molecular data, crucial to enable the development of a comprehensive and personalized data-driven diagnostic approach in disease management and fostering the development of computational predictive models. This work aims to frame this perspective, first by evaluating the state of standardization of individual diagnostic domains and then by identifying challenges and proposing a possible solution towards an integrative approach that can guarantee the suitability of information that can be shared through a digital biobank. Our analysis of the state of the art shows the presence and use of reference standards in biobanks and, generally, digital repositories for each specific domain. Despite this, standardization to guarantee the integration and reproducibility of the numerical descriptors generated by each domain, e.g. radiomic, pathomic and -omic features, is still an open challenge. Based on specific use cases and scenarios, an integration model, based on the JSON format, is proposed that can help address this problem. Ultimately, this work shows how, with specific standardization and promotion efforts, the digital biobank model can become an enabling technology for the comprehensive study of diseases and the effective development of data-driven technologies at the service of precision medicine.
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Affiliation(s)
| | - Giuseppina Esposito
- Bio Check Up S.R.L, 80121, Naples, Italy
- Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131, Naples, Italy
| | | | | | - Peppino Mirabelli
- UOS Laboratori di Ricerca e Biobanca, AORN Santobono-Pausilipon, Via Teresa Ravaschieri, 8, 80122, Naples, Italy
| | - Camilla Scapicchio
- Academic Radiology, Department of Translational Research, University of Pisa, via Roma, 67, 56126, Pisa, Italy
| | - Rita Borgheresi
- Academic Radiology, Department of Translational Research, University of Pisa, via Roma, 67, 56126, Pisa, Italy
| | - Emanuele Neri
- Academic Radiology, Department of Translational Research, University of Pisa, via Roma, 67, 56126, Pisa, Italy
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15
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Kamenskikh EM, Krygina AY, Gomboeva SC, Zhailebaeva D, Koval DP, Kicherov NA, Otchurzhap CN, Birulina YG, Alifirova VM. [Biobanking in clinical trials involving multiple sclerosis patients]. Zh Nevrol Psikhiatr Im S S Korsakova 2024; 124:7-15. [PMID: 39175234 DOI: 10.17116/jnevro20241240727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/24/2024]
Abstract
Investigation of multiple sclerosis (MS) pathogenesis requires sophisticated analytical tools of precision medicine, such as omics research, which include genomics, microbiomics and metabolomics (proteomics, lipidomics and glycomics). Such sensitive methods are based on careful preanalytical work with biomaterials to maintain quality and obtain objective results. Implementation of biobanking as a universal method for working with biomaterials will help to standardize the stages of research, compare different scientific team's results. Collaboration of MS researchers with large biobanks can also help to conduct multicenter and long-term prospective studies, to include a wide number of patients. In this article, we analyze the experience of biobanking practice technologies in studies of MS patients and share the experience of partnership between the Center for MS of the Tomsk Region and the Bank of Biological Material of the Siberian State Medical University.
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Affiliation(s)
| | - A Yu Krygina
- Siberian State Medical University, Tomsk, Russia
| | | | | | - D P Koval
- Siberian State Medical University, Tomsk, Russia
| | - N A Kicherov
- Siberian State Medical University, Tomsk, Russia
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16
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Winz C, Zong WX, Suh N. Endocrine-disrupting compounds and metabolomic reprogramming in breast cancer. J Biochem Mol Toxicol 2023; 37:e23506. [PMID: 37598318 PMCID: PMC10840637 DOI: 10.1002/jbt.23506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 06/23/2023] [Accepted: 08/11/2023] [Indexed: 08/21/2023]
Abstract
Endocrine-disrupting chemicals pose a growing threat to human health through their increasing presence in the environment and their potential interactions with the mammalian endocrine systems. Due to their structural similarity to hormones like estrogen, these chemicals can interfere with endocrine signaling, leading to many deleterious effects. Exposure to estrogenic endocrine-disrupting compounds (EDC) is a suggested risk factor for the development of breast cancer, one of the most frequently diagnosed cancers in women. However, the mechanisms through which EDCs contribute to breast cancer development remain elusive. To rapidly proliferate, cancer cells undertake distinct metabolic programs to utilize existing nutrients in the tumor microenvironment and synthesize macromolecules de novo. EDCs are known to dysregulate cell signaling pathways related to cellular metabolism, which may be an important mechanism through which they exert their cancer-promoting effects. These altered pathways can be studied via metabolomic analysis, a new advancement in -omics technologies that can interrogate molecular pathways that favor cancer development and progression. This review will summarize recent discoveries regarding EDCs and the metabolic reprogramming that they may induce to facilitate the development of breast cancer.
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Affiliation(s)
- Cassandra Winz
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
- Department of Pharmacology and Toxicology, Environmental and Occupational Health Sciences Institute, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
| | - Wei-Xing Zong
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
- Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA
| | - Nanjoo Suh
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
- Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA
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17
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Senavirathna L, Pan S, Chen R. Protein Advanced Glycation End Products and Their Implications in Pancreatic Cancer. Cancer Prev Res (Phila) 2023; 16:601-610. [PMID: 37578815 PMCID: PMC10843555 DOI: 10.1158/1940-6207.capr-23-0162] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 07/14/2023] [Accepted: 08/10/2023] [Indexed: 08/15/2023]
Abstract
Protein advanced glycation end products (AGE) formed by nonenzymatic glycation can disrupt the normal structure and function of proteins, and stimulate the receptor for AGEs (RAGE), triggering intricate mechanisms that are etiologically related to various chronic diseases, including pancreatic cancer. Many common risk factors of pancreatic cancer are the major sources for the formation of protein AGEs and glycative stress in the human body. Abnormal accumulation of protein AGEs can impair the cellular proteome and promote AGE-RAGE driven pro-inflammatory signaling cascades, leading to increased oxidative stress, protease resistance, protein dysregulation, transcription activity of STAT, NF-κB, and AP-1, aberrant status in ubiquitin-proteasome system and autophagy, as well as other molecular events that are susceptible for the carcinogenic transformation towards the development of neoplasms. Here, we review studies to highlight our understanding in the orchestrated molecular events in bridging the impaired proteome, dysregulated functional networks, and cancer hallmarks initiated upon protein AGE formation and accumulation in pancreatic cancer.
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Affiliation(s)
- Lakmini Senavirathna
- The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Sheng Pan
- The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
- Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Ru Chen
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
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18
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Broderick K, Moutaoufik MT, Aly KA, Babu M. Sanitation enzymes: Exquisite surveillance of the noncanonical nucleotide pool to safeguard the genetic blueprint. Semin Cancer Biol 2023; 94:11-20. [PMID: 37211293 DOI: 10.1016/j.semcancer.2023.05.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 05/14/2023] [Accepted: 05/17/2023] [Indexed: 05/23/2023]
Abstract
Reactive oxygen species (ROS) are common products of normal cellular metabolism, but their elevated levels can result in nucleotide modifications. These modified or noncanonical nucleotides often integrate into nascent DNA during replication, causing lesions that trigger DNA repair mechanisms such as the mismatch repair machinery and base excision repair. Four superfamilies of sanitization enzymes can effectively hydrolyze noncanonical nucleotides from the precursor pool and eliminate their unintended incorporation into DNA. Notably, we focus on the representative MTH1 NUDIX hydrolase, whose enzymatic activity is ostensibly nonessential under normal physiological conditions. Yet, the sanitization attributes of MTH1 are more prevalent when ROS levels are abnormally high in cancer cells, rendering MTH1 an interesting target for developing anticancer treatments. We discuss multiple MTH1 inhibitory strategies that have emerged in recent years, and the potential of NUDIX hydrolases as plausible targets for the development of anticancer therapeutics.
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Affiliation(s)
- Kirsten Broderick
- Department of Biochemistry, University of Regina, Regina, Saskatchewan, Canada
| | | | - Khaled A Aly
- Department of Biochemistry, University of Regina, Regina, Saskatchewan, Canada
| | - Mohan Babu
- Department of Biochemistry, University of Regina, Regina, Saskatchewan, Canada.
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19
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Hayden H, Klopf J, Ibrahim N, Knöbl V, Sotir A, Mekis R, Nowikovsky K, Eilenberg W, Neumayer C, Brostjan C. Quantitation of oxidized nuclear and mitochondrial DNA in plasma samples of patients with abdominal aortic aneurysm. Free Radic Biol Med 2023; 206:94-105. [PMID: 37353175 DOI: 10.1016/j.freeradbiomed.2023.06.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 06/06/2023] [Accepted: 06/15/2023] [Indexed: 06/25/2023]
Abstract
There is accumulating evidence that pro-inflammatory features are inherent to mitochondrial DNA and oxidized DNA species. 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) is the most frequently studied oxidatively generated lesion. Modified DNA reaches the circulation upon cell apoptosis, necrosis or neutrophil extracellular trap (NET) formation. Standard chromatography-based techniques for the assessment of 8-oxodGuo imply degradation of DNA to a single base level, thus precluding the attribution to a nuclear or mitochondrial origin. We therefore aimed to establish a protocol for the concomitant assessment of oxidized mitochondrial and nuclear DNA from human plasma samples. We applied immunoprecipitation (IP) for 8-oxodGuo to separate oxidized from non-oxidized DNA species and subsequent quantitative polymerase chain reaction (qPCR) to assign them to their subcellular source. The IP procedure failed when applied directly to plasma samples, i.e. isotype control precipitated similar amounts of DNA as the specific 8-oxodGuo antibody. In contrast, DNA isolation from plasma prior to the IP process provided assay specificity with little impact on DNA oxidation status. We further optimized sensitivity and efficiency of qPCR analysis by reducing amplicon length and targeting repetitive nuclear DNA elements. When the established protocol was applied to plasma samples of abdominal aortic aneurysm (AAA) patients and control subjects, the AAA cohort displayed significantly elevated circulating non-oxidized and total nuclear DNA and a trend for increased levels of oxidized mitochondrial DNA. An enrichment of mitochondrial versus nuclear DNA within the oxidized DNA fraction was seen for AAA patients. Regarding the potential source of circulating DNA, we observed a significant correlation of markers of neutrophil activation and NET formation with nuclear DNA, independent of oxidation status. Thus, the established method provides a tool to detect and distinguish the release of oxidized nuclear and mitochondrial DNA in human plasma and offers a refined biomarker to monitor disease conditions of pro-inflammatory cell and tissue destruction.
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Affiliation(s)
- Hubert Hayden
- Department of General Surgery, Division of Vascular Surgery, Medical University of Vienna and University Hospital Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Johannes Klopf
- Department of General Surgery, Division of Vascular Surgery, Medical University of Vienna and University Hospital Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Nahla Ibrahim
- Department of General Surgery, Division of Vascular Surgery, Medical University of Vienna and University Hospital Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Viktoria Knöbl
- Department of General Surgery, Division of Vascular Surgery, Medical University of Vienna and University Hospital Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Anna Sotir
- Department of General Surgery, Division of Vascular Surgery, Medical University of Vienna and University Hospital Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Ronald Mekis
- Institute of Physiology, Pathophysiology and Biophysics, Unit of Physiology and Biophysics, University of Veterinary Medicine, 1210, Vienna, Austria
| | - Karin Nowikovsky
- Institute of Physiology, Pathophysiology and Biophysics, Unit of Physiology and Biophysics, University of Veterinary Medicine, 1210, Vienna, Austria
| | - Wolf Eilenberg
- Department of General Surgery, Division of Vascular Surgery, Medical University of Vienna and University Hospital Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Christoph Neumayer
- Department of General Surgery, Division of Vascular Surgery, Medical University of Vienna and University Hospital Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Christine Brostjan
- Department of General Surgery, Division of Vascular Surgery, Medical University of Vienna and University Hospital Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
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20
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Alhassan HH, Al-Keridis LA, Ayub H, Alenazy FO, Alruwaili Y, Khan MR, Fatima M, Patel M, Alshammari N, Adnan M, Sahreen S. GC-MS-based profiling and ameliorative potential of Carissa opaca Stapf ex Haines fruit against cardiac and testicular toxicity: An In vivo study. Heliyon 2023; 9:e19324. [PMID: 37664756 PMCID: PMC10469965 DOI: 10.1016/j.heliyon.2023.e19324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 06/26/2023] [Accepted: 08/18/2023] [Indexed: 09/05/2023] Open
Abstract
Fruit of Carissa opaca Stapf ex Haines (C. opaca) is a feed additive and is commonly used against cardiac dysfunction, fever, asthma, diarrhea, gastrointestinal ailments, and skin diseases. In this study, we aimed to evaluate the metabolic profile and antioxidant potential of C. opaca fruit against carbon tetrachloride (CCl4)-induced cardiotoxicity and testicular toxicity in rats. Gas Chromatoghraphy-Mass Spectrometry (GC-MS) analysis of C. opaca fruit for the identification of potential metabolic profile, followed by methanolic extract of C. opaca and its derived fractions including n-hexane, ethyl acetate, chloroform, butanol, and aqueous were used to assess the antioxidant potential of fruits. Ten groups of rats received different treatments and got evaluated for cardiac and testicular antioxidant enzymes, histological architecture, and serum hormonal levels. GC-MS analysis of methanolic extract of C. opaca fruit showed the presence of some bioactive metabolites like cyclodecane, diethyl 2,6-pyridine dicarboxylate, tetrahydro-geraniol, S-[2-[N, N-Dimethylamino]ethyl]morpoline, 2,3-Methylenedioxyphenol, alpha-d-Glucopyranoside, 5,10-Diethoxy-2,3,7,8-tetrahydro-1H, 6H-dipyrrolo [1,2-a; 1',2'-d] pyrazine and 1,3-Benzothiazol-2(3H)-one,3-(3,3-dimethyl-1-oxobutyl) that corresponds the medicinal properties of C. opaca fruit. Prepared fractions of C. opaca fruits mitigated the toxicity induced by CCl4 in the heart and testicular tissues of rats. Oxidative stress was caused by the inhibition of activities of glutathione and other antioxidant enzymes of the body, while on the other hand elevating the levels of nitrite and hydrogen peroxide. Treatment with C. opaca fruit extract normalized the levels of enzymes, reproductive hormones, and free radicals thus restoring the histopathological and enzymatic biomarkers towards the normal group. The study supports the indigenous use of fruits as an alternative medicine against cardiac dysfunction by providing scientific evidence of protection against CCl4-induced injuries, and it also concludes the antioxidant defensive role in testicular tissues.
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Affiliation(s)
- Hassan H. Alhassan
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences-Sakaka, Jouf University, Saudi Arabia
| | - Lamya Ahmed Al-Keridis
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia
| | - Huma Ayub
- Department of Zoology, Mirpur University of Science & Technology, Azad Jammu and Kashmir AJK, Mirpur, Pakistan
| | - Fawaz O. Alenazy
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences-Sakaka, Jouf University, Saudi Arabia
| | - Yasir Alruwaili
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences-Sakaka, Jouf University, Saudi Arabia
| | - Muhammad Rashid Khan
- Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Mehreen Fatima
- Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Mitesh Patel
- Research and Development Cell, Department of Biotechnology, Parul Institute of Applied Sciences, Parul University, Vadodara, 391760, India
| | - Nawaf Alshammari
- Department of Biology, College of Science, University of Hail, Hail, P O Box 2440, Saudi Arabia
| | - Mohd Adnan
- Department of Biology, College of Science, University of Hail, Hail, P O Box 2440, Saudi Arabia
| | - Sumaira Sahreen
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), Pulau Pinang, 11800, Malaysia
- Botanical Sciences Division, Pakistan Museum of Natural History, Garden Avenue, Shakarparian Road, 44000, Islamabad, Pakistan
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21
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Lucot KL, Suarez W, Mifflin K, DeCarli C, La Grande J, Dugger BN. Assessment of Current Practices Across Alzheimer's Disease Research Centers Biorepositories. Biopreserv Biobank 2023; 21:282-287. [PMID: 35856794 PMCID: PMC10282793 DOI: 10.1089/bio.2022.0022] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
In 1984, the National Institute on Aging developed the Alzheimer's disease centers program. The main goal of these centers is to advance the understanding of Alzheimer's disease and related dementias (ADRD) through comprehensive patient evaluations and cutting-edge research in pathology, laboratory medicine, education, and scientific discovery. The neuropathology core of the Alzheimer's Disease Research Centers (ADRCs) collects postmortem brain tissue from consented donors ranging from cognitively normal individuals to those with late-stage dementia, whose samples and data can be shared around the world to further advance knowledge, diagnosis, and to eventually find cures for ADRD. Although recommended guidelines for biorepositories exist, we aimed to understand the current practices within neuropathology cores across the ADRCs. A survey was developed that focused on information related to sample processing methods, biospecimen requests, financial costs related to the repository, and data management. This survey was distributed to 28 current and former ADRC neuropathology cores. The survey obtained a response rate of 82% (23/28). Although most centers were consistent in responses related to sample processing and storage, they varied widely in processes by which neuropathological samples are shared and cost recovery mechanisms. The results of this survey provide benchmark data on practices within neuropathology cores across ADRCs and the overlap with biorepository best practices. Future studies focused on understanding factors that may influence current practices (such as available funds and personnel) are need to aid in minimizing barriers to optimally follow best practices. Sharing these data among ADRCs will allow for improvement in workflows and working toward cures for ADRD.
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Affiliation(s)
- Katherine L. Lucot
- Department of Pathology and Laboratory Medicine, School of Medicine, University of California, Davis, Sacramento, California, USA
| | - Welver Suarez
- Gerontology Program, California State University, Sacramento, Sacramento, California, USA
| | - Kelsey Mifflin
- Department of Pathology and Laboratory Medicine, School of Medicine, University of California, Davis, Sacramento, California, USA
| | - Charles DeCarli
- Department of Neurology, School of Medicine, University of California, Davis, Sacramento, California, USA
| | - Jayne La Grande
- Department of Neurology, School of Medicine, University of California, Davis, Sacramento, California, USA
| | - Brittany N. Dugger
- Department of Pathology and Laboratory Medicine, School of Medicine, University of California, Davis, Sacramento, California, USA
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22
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Bettio V, Mazzucco E, Aleni C, Cracas S, Rinaldi C, Antona A, Varalda M, Venetucci J, Ferrante D, Rimedio A, Capello D. UPO Biobank: The Challenge of Integrating Biobanking into the Academic Environment to Support Translational Research. J Pers Med 2023; 13:911. [PMID: 37373900 DOI: 10.3390/jpm13060911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 05/18/2023] [Accepted: 05/26/2023] [Indexed: 06/29/2023] Open
Abstract
Biobanks are driving motors of precision and personalized medicine by providing high-quality biological material/data through the standardization and harmonization of their collection, preservation, and distribution. UPO Biobank was established in 2020 as an institutional, disease, and population biobank within the University of Piemonte Orientale (UPO) for the promotion and support of high-quality, multidisciplinary studies. UPO Biobank collaborates with UPO researchers, sustaining academic translational research, and supports the Novara Cohort Study, a longitudinal cohort study involving the population in the Novara area that will collect data and biological specimens that will be available for epidemiological, public health, and biological studies on aging. UPO Biobank has been developed by implementing the quality standards for the field and the ethical and legal issues and normative about privacy protection, data collection, and sharing. As a member of the "Biobanking and Biomolecular Resources Research Infrastructure" (BBMRI) network, UPO Biobank aims to expand its activity worldwide and launch cooperation with new national and international partners and researchers. The objective of this manuscript is to report an institutional and operational experience through the description of the technical and procedural solutions and ethical and scientific implications associated with the establishment of this university research biobank.
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Affiliation(s)
- Valentina Bettio
- UPO Biobank, University of Piemonte Orientale, 28100 Novara, Italy
- Department of Translational Medicine, Center of Excellence in Aging Sciences, University of Piemonte Orientale, 28100 Novara, Italy
| | - Eleonora Mazzucco
- UPO Biobank, University of Piemonte Orientale, 28100 Novara, Italy
- Department of Translational Medicine, Center of Excellence in Aging Sciences, University of Piemonte Orientale, 28100 Novara, Italy
| | - Chiara Aleni
- Department of Sustainable Development and Ecological Transition, University of Piemonte Orientale, 13100 Vercelli, Italy
| | - Silvia Cracas
- Department of Translational Medicine, Center of Excellence in Aging Sciences, University of Piemonte Orientale, 28100 Novara, Italy
| | - Carmela Rinaldi
- Department of Translational Medicine, Center of Excellence in Aging Sciences, University of Piemonte Orientale, 28100 Novara, Italy
- Learning and Research Area, A.O.U. Maggiore della Carità, 28100 Novara, Italy
| | - Annamaria Antona
- Department of Translational Medicine, Center of Excellence in Aging Sciences, University of Piemonte Orientale, 28100 Novara, Italy
| | - Marco Varalda
- Department of Translational Medicine, Center of Excellence in Aging Sciences, University of Piemonte Orientale, 28100 Novara, Italy
| | - Jacopo Venetucci
- Department of Translational Medicine, Center of Excellence in Aging Sciences, University of Piemonte Orientale, 28100 Novara, Italy
| | - Daniela Ferrante
- Department of Translational Medicine, Center of Excellence in Aging Sciences, University of Piemonte Orientale, 28100 Novara, Italy
| | - Antonio Rimedio
- Ethics Committee of the University "Hospital Major of Charity" in Novara, Local Health Authorities Biella, 28100 Novara, Italy
| | - Daniela Capello
- UPO Biobank, University of Piemonte Orientale, 28100 Novara, Italy
- Department of Translational Medicine, Center of Excellence in Aging Sciences, University of Piemonte Orientale, 28100 Novara, Italy
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23
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Larsen EL, Andersen A, Kjaer LK, Eickhoff MK, Frimodt-Møller M, Persson F, Rossing P, Lykkesfeldt J, Knop FK, Vilsbøll T, Rungby J, Poulsen HE. Effects of Two- and Twelve-Weeks Sodium-Glucose Cotransporter 2 Inhibition on DNA and RNA Oxidation: Two Randomized, Placebo-Controlled Trials. Free Radic Res 2023:1-12. [PMID: 37171199 DOI: 10.1080/10715762.2023.2213820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/13/2023]
Abstract
Animal studies have shown that SGLT2 inhibition decreases oxidative stress, which may explain the cardiovascular protective effects observed following SGLT2 inhibition treatment. Thus, we investigated the effects of two and twelve weeks SGLT2 inhibition on DNA and RNA oxidation. Individuals with type 2 diabetes (n = 31) were randomized to two weeks of treatment with the SGLT2 inhibitor empagliflozin treatment (25 mg once daily) or placebo. The primary outcome was changes in DNA and RNA oxidation measured as urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), respectively. In another trial, individuals with type 2 diabetes (n = 35) were randomized to twelve weeks of dapagliflozin treatment (10 mg once daily) or placebo in a crossover study. Changes in urinary excretion of 8-oxodG and 8-oxoGuo were investigated as a post-hoc analysis. Compared with placebo treatment, two weeks of empagliflozin treatment did not change urinary excretion of 8-oxodG (between-group difference: 0.3 nmol/24-hour (95% CI: -4.2 to 4.8)) or 8-oxoGuo (1.3 nmol/24-hour (95% CI: -4.7 to 7.3)). From a mean baseline 8-oxodG/creatinine urinary excretion of 1.34 nmol/mmol, dapagliflozin-treated individuals changed 8-oxodG/creatinine by -0.17 nmol/mmol (95% CI: -0.29 to -0.04) following twelve weeks of treatment, whereas placebo-treated individuals did not change 8-oxodG/creatinine (within-group effect: 0.10 nmol/mmol (95% CI: -0.02 to 0.22)) resulting in a significant between-group difference (P = 0.01). Urinary excretion of 8-oxoGuo was unaffected by dapagliflozin treatment. In conclusion, two weeks of empagliflozin treatment did not change DNA or RNA oxidation. However, a post-hoc analysis revealed that longer term dapagliflozin treatment decreased DNA oxidation. Clinicaltrials.gov: NCT02890745 and NCT02914691.HighlightsPlasma ferritin correlated with DNA and RNA oxidation in individuals with T2DTwelve weeks dapagliflozin treatment decreased DNA oxidationDapagliflozin and empagliflozin treatment did not change RNA oxidationLipid peroxidation was unaffected by two weeks empagliflozin treatment.
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Affiliation(s)
- Emil L Larsen
- Department of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
- Department of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Andreas Andersen
- Steno Diabetes Center Copenhagen, Herlev, Denmark
- Center for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark
| | - Laura K Kjaer
- Department of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
| | | | | | | | - Peter Rossing
- Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jens Lykkesfeldt
- Department of Veterinary and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark
| | - Filip K Knop
- Steno Diabetes Center Copenhagen, Herlev, Denmark
- Center for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Tina Vilsbøll
- Steno Diabetes Center Copenhagen, Herlev, Denmark
- Center for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jørgen Rungby
- Center for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark
- Department of Endocrinology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
- Copenhagen Center for Translational Research, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
| | - Henrik E Poulsen
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Endocrinology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
- Department of Cardiology, Copenhagen University Hospital - North Zealand, Hillerød, Denmark
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24
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Zhong H, Yang L, Zeng Q, Chen W, Zhao H, Wu L, Qin L, Yu QQ. Machine Learning Predicts the Oxidative Stress Subtypes Provide an Innovative Insight into Colorectal Cancer. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2023; 2023:1737501. [PMID: 37122535 PMCID: PMC10147531 DOI: 10.1155/2023/1737501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 10/27/2022] [Accepted: 11/25/2022] [Indexed: 05/02/2023]
Abstract
So far, it has been reached the academic consensus that the molecular subtypes are via genomic heterogeneity and immune infiltration patterns. Considering that oxidative stress (OS) is involved in tumorigenesis and prognosis prediction, we propose an innovative classification of colorectal cancer- (CRC-) OS subtypes. We obtain three datasets from The Cancer Genome Atlas Program (TCGA) and Gene Expression Omnibus (GEO) online databases. 1399 OS-related genes were selected from the GeneCards database. We remove the batch effect before conducting differentially expressed genes (DEGs) analyses between normal and tumor samples. Nonnegative matrix factorization (NMF) was used to perform an unsupervised cluster. Lasso regression and Cox regression were used to construct the signature model. DEGs, robust rank aggregation, and protein-protein interaction networks were used to select hub genes, and then use hub genes to predict OS subtypes by random forest algorithms. NMF identifies two OS-related subtypes of CRC patients. Eight OS-related gene signatures were built to predict the outcome of patients, based on the DEGs between two subtypes. A total of 61 DEGs overlap each dataset, and the RRA analysis shows that 17 genes are important in these three datasets, and 15 genes are shared genes between the two methods. PPI network suggests that five hub genes are confirmed, they are SPP1, SERPINE1, CAV1, PDGFRB, and PLAU. These five hub genes could predict the OS-related subtype of CRC accurately with AUC equal to 0.771. In our study, we identify two OS-related subtypes, which will provide an innovative insight into colorectal cancer.
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Affiliation(s)
- Haitao Zhong
- Jining First People's Hospital, Jining Medical University, Jining 272000, China
| | - Le Yang
- Jining First People's Hospital, Jining Medical University, Jining 272000, China
| | - Qingshang Zeng
- Shanghai Tianyou Hospital, Tongji University, Shanghai 200333, China
| | - Weidong Chen
- Jining First People's Hospital, Jining Medical University, Jining 272000, China
| | - Haibo Zhao
- Jining First People's Hospital, Jining Medical University, Jining 272000, China
| | - Linlin Wu
- Department of Oncology, Tengzhou Central People's Hospital Affiliated to Jining Medical College, Tengzhou 277500, China
| | - Lei Qin
- Jining First People's Hospital, Jining Medical University, Jining 272000, China
| | - Qing-Qing Yu
- Jining First People's Hospital, Jining Medical University, Jining 272000, China
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25
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Berdiaki A, Neagu M, Spyridaki I, Kuskov A, Perez S, Nikitovic D. Hyaluronan and Reactive Oxygen Species Signaling—Novel Cues from the Matrix? Antioxidants (Basel) 2023; 12:antiox12040824. [PMID: 37107200 PMCID: PMC10135151 DOI: 10.3390/antiox12040824] [Citation(s) in RCA: 45] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 03/22/2023] [Accepted: 03/24/2023] [Indexed: 03/30/2023] Open
Abstract
Hyaluronan (HA) is a naturally occurring non-sulfated glycosaminoglycan (GAG) localized to the cell surface and the tissue extracellular matrix (ECM). It is composed of disaccharides containing glucuronic acid and N-acetylglucosamine, is synthesized by the HA synthase (HAS) enzymes and is degraded by hyaluronidase (HYAL) or reactive oxygen and nitrogen species (ROS/RNS) actions. HA is deposited as a high molecular weight (HMW) polymer and degraded to low molecular weight (LMW) fragments and oligosaccharides. HA affects biological functions by interacting with HA-binding proteins (hyaladherins). HMW HA is anti-inflammatory, immunosuppressive, and antiangiogenic, whereas LMW HA has pro-inflammatory, pro-angiogenetic, and oncogenic effects. ROS/RNS naturally degrade HMW HA, albeit at enhanced levels during tissue injury and inflammatory processes. Thus, the degradation of endothelial glycocalyx HA by increased ROS challenges vascular integrity and can initiate several disease progressions. Conversely, HA exerts a vital role in wound healing through ROS-mediated HA modifications, which affect the innate immune system. The normal turnover of HA protects against matrix rigidification. Insufficient turnover leads to increased tissue rigidity, leading to tissue dysfunction. Both endogenous and exogenous HMW HA have a scavenging capacity against ROS. The interactions of ROS/RNS with HA are more complex than presently perceived and present an important research topic.
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26
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Tew DJ, Hebert JM, Schmier BJ. Discovery and properties of a monoclonal antibody targeting 8-oxoA, an oxidized adenine lesion in DNA and RNA. Redox Biol 2023; 62:102658. [PMID: 36989571 PMCID: PMC10074937 DOI: 10.1016/j.redox.2023.102658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 03/04/2023] [Indexed: 03/17/2023] Open
Abstract
8-oxoA, a major oxidation product of adenosine, is a mispairing, mutagenic lesion that arises in DNA and RNA when •OH radicals or one-electron oxidants attack the C8 adenine atom or polymerases misincorporate 8-oxo(d)ATP. The danger of 8-oxoA is underscored by the existence of dedicated cellular repair machinery that explicitly excise it from DNA, the attenuation of translation induced by 8-oxoA-mRNA or damaged ribosomes, and its potency as a TLR7 agonist. Here we present the discovery, purification, and biochemical characterization of a new mouse IgGk1 monoclonal antibody (6E4) that specifically targets 8-oxoA. Utilizing an AchE-based competitive ELISA assay, we demonstrate the selectivity of 6E4 for 8-oxoA over a plethora of canonical and chemically modified nucleosides including 8-oxoG, A, m6A, 2-oxoA, and 5-hoU. We further show the ability of 6E4 to exclusively recognize 8-oxoA in nucleoside triphosphates (8-oxoATP) and DNA/RNA oligonucleotides containing a single 8-oxoA. 6E4 also binds 8-oxoA in duplex DNA/RNA antigens where the lesion is either paired correctly or base mismatched. Our findings define the 8-oxoAde nucleobase as the critical epitope and indicate mAb 6E4 is ideally suited for a broad range of immunological applications in nucleic acid detection and quality control.
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27
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Jayawardana TK, Hossain MF, Patel D, Kimura SY. Haloacetonitrile stability in cell culture media used in vitro toxicological studies. CHEMOSPHERE 2023; 313:137568. [PMID: 36529179 DOI: 10.1016/j.chemosphere.2022.137568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 12/12/2022] [Accepted: 12/13/2022] [Indexed: 06/17/2023]
Abstract
Haloacetonitriles (HANs) are an emerging class of nitrogenous disinfection by-products (DBPs) formed in disinfected drinking water and have been reported to be more cyto- and genotoxic than the regulated DBPs. HANs are also known to hydrolyze under neutral pH and normal room temperature. However, the stability of HANs has not been well characterized in DBP toxicological assessments. Most toxicological assessments expose DBPs up to several days which may result in a mixture of HANs and degradation products that might have underestimated HAN toxicity. In this study, HANs stability was characterized in 1) a buffer solution in sealed vials, 2) cell culture media (CCM) in sealed vials, and 3) CCM in 96 sealed well plates with 5% CO2. Solutions were incubated at 37 °C for 3 days. MonoHANs were found to be stable in buffer and CCM except when HANs were incubated in CCM in plates where they could possibly be affected by volatilization and photodegradation during sample handling. However, di- and tri- HANs degraded between 70 and 100% in both buffer solution and CCM. They were also found to be less stable in CCM than in buffer solution possibly from HANs reacting with nucleophiles present in CCM (i.e., amino acids). Identified degradation products include corresponding haloacetamides and haloacetic acids for buffer solutions and only haloacetic acids and an unknown brominated compound for CCM. Results of this study suggests that reported toxicity values might have been underestimated and should consider changing CCM and DBP on a daily basis for a more accurate toxicity measurement.
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Affiliation(s)
- Thilina K Jayawardana
- University of Calgary, Department of Chemistry, 2500 University Dr. NW, Calgary, AB, T2N 1N4, Canada
| | - Md Fahim Hossain
- University of Calgary, Department of Chemistry, 2500 University Dr. NW, Calgary, AB, T2N 1N4, Canada
| | - Dhruvin Patel
- University of Calgary, Department of Chemistry, 2500 University Dr. NW, Calgary, AB, T2N 1N4, Canada
| | - Susana Y Kimura
- University of Calgary, Department of Chemistry, 2500 University Dr. NW, Calgary, AB, T2N 1N4, Canada.
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28
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Multifactorial Diseases of the Heart, Kidneys, Lungs, and Liver and Incident Cancer: Epidemiology and Shared Mechanisms. Cancers (Basel) 2023; 15:cancers15030729. [PMID: 36765688 PMCID: PMC9913123 DOI: 10.3390/cancers15030729] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 01/05/2023] [Accepted: 01/20/2023] [Indexed: 01/26/2023] Open
Abstract
Within the aging population, the frequency of cancer is increasing dramatically. In addition, multiple genetic and environmental factors lead to common multifactorial diseases, including cardiovascular disease, chronic kidney disease, chronic obstructive pulmonary disease, and metabolic-associated fatty liver disease. In recent years, there has been a growing awareness of the connection between cancer and multifactorial diseases, as well as how one can affect the other, resulting in a vicious cycle. Although the exact mechanistic explanations behind this remain to be fully explored, some progress has been made in uncovering the common pathologic mechanisms. In this review, we focus on the nature of the link between cancer and common multifactorial conditions, as well as specific shared mechanisms, some of which may represent either preventive or therapeutic targets. Rather than organ-specific interactions, we herein focus on the shared mechanisms among the multifactorial diseases, which may explain the increased cancer risk. More research on this subject will highlight the significance of developing new drugs that target multiple systems rather than just one disease.
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29
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Li S, Yuan Y, Wang X, Cai L, Wang J, Zhao Y, Jiang L, Yang X. Bioaccumulation and toxicity of terbuthylazine in earthworms (Eisenia fetida). ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2023; 97:104016. [PMID: 36435387 DOI: 10.1016/j.etap.2022.104016] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 08/15/2022] [Accepted: 11/16/2022] [Indexed: 06/16/2023]
Abstract
Terbuthylazine is an effective and widely used s-triazine herbicide. However, limited data exists on its toxicity and bioaccumulation in earthworms (Eisenia fetida). In this study, we investigated the bioaccumulation, antioxidant enzyme activity, detoxification enzyme activity, and DNA damage in earthworms when exposed to terbuthylazine. The results indicated that terbuthylazine in soil had low bioaccumulation in earthworms and the biota-soil accumulation factors of terbuthylazine declined with an increasing soil terbuthylazine concentration. In the enzyme activity assays, the superoxide dismutase (SOD), catalase (CAT), and glutathione-S-transferase (GST) activities showed upward trends when compared with the control. The carboxylesterase (CarE) activity increased on day 21. The 8-hydroxy-2-deoxyguanosine (8-OHdG) content, a DNA damage bioindicator, was higher than that of the control on day 21. Combined with the integrated biological response index version 2 analysis, these results can provide a comprehensive evaluation of the toxicological effects that terbuthylazine has on earthworms and soil ecosystems.
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Affiliation(s)
- Shun Li
- Safety Evaluation Center, Shenyang SYRICI Test Co. Ltd, Shenyang 110027, China; Shenyang Research Institute of Chemical Industry, Shenyang 110021, China
| | - Ye Yuan
- Safety Evaluation Center, Shenyang SYRICI Test Co. Ltd, Shenyang 110027, China; Shenyang Research Institute of Chemical Industry, Shenyang 110021, China
| | - Xing Wang
- Safety Evaluation Center, Shenyang SYRICI Test Co. Ltd, Shenyang 110027, China
| | - Leiming Cai
- Safety Evaluation Center, Shenyang SYRICI Test Co. Ltd, Shenyang 110027, China; Shenyang Research Institute of Chemical Industry, Shenyang 110021, China.
| | - Jiao Wang
- Safety Evaluation Center, Shenyang SYRICI Test Co. Ltd, Shenyang 110027, China
| | - Yuanji Zhao
- Safety Evaluation Center, Shenyang SYRICI Test Co. Ltd, Shenyang 110027, China
| | - Lei Jiang
- Safety Evaluation Center, Shenyang SYRICI Test Co. Ltd, Shenyang 110027, China; Shenyang Research Institute of Chemical Industry, Shenyang 110021, China
| | - Xu Yang
- Safety Evaluation Center, Shenyang SYRICI Test Co. Ltd, Shenyang 110027, China; Shenyang Research Institute of Chemical Industry, Shenyang 110021, China
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30
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Gao Z, Huang Y, Yao F, Zhou Z. Public awareness and attitudes toward biobank and sample donation: A regional Chinese survey. Front Public Health 2022; 10:1025775. [PMID: 36504979 PMCID: PMC9727410 DOI: 10.3389/fpubh.2022.1025775] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 11/08/2022] [Indexed: 11/24/2022] Open
Abstract
Background The biobank is an extraordinary aid to research and scientific progress. Public involvement in biobanks, necessary for their development, is limited due to inadequate knowledge of biobanking and concerns about sample donation. This study explores the effectiveness of different publicity methods in improving participants' willingness to donate, and assesses public motivations and concerns. It aims to identify an efficient method of improving participants' awareness of biobanking and promoting sample donation. Methods A structured 20-item questionnaire was formulated to evaluate participants' knowledge of and attitudes toward biobanks and sample donation. In total, 1,500 questionnaires were disseminated to three groups of 500 participants who received, respectively, picture-based promotional material, text-based promotional material, or who attended a biobank-related lecture. Of these, 945 completed questionnaires were received. All the participants completed the questionnaires twice, before and after the corresponding publicity education. Results After each of the three methods of publicity based on text, pictures and a lecture, respondents' willingness to donate samples was significantly increased (P < 0.001), the lecture being more effective than the other two methods (P = 0.001). Participants with a medical background were more willing to donate biospecimens after publicity than those without medical backgrounds (P < 0.005) but had common motivations for donation including altruism and aiding medical research. The main concern hindering respondents' willingness to donate was the security of personal information. Conclusion Different types of biobank-related publicity based on text material, pictorial material and a lecture all improved respondents' willingness to donate and reduced concerns regarding sample donation. Medical background was a critical factor affecting attitudes toward sample donation after publicity. The results of this study suggest strategies that may popularize biobanks and enhance sample donation, further promoting the development of biobanks.
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Affiliation(s)
- Zhaolin Gao
- Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, China,Hunan Key Laboratory of Ophthalmology, Central South University, Changsha, China
| | - Yanxia Huang
- Center for Experimental Medicine, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Fei Yao
- Hunan Key Laboratory of Ophthalmology, Central South University, Changsha, China
| | - Ziyu Zhou
- The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China,Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China,*Correspondence: Ziyu Zhou
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31
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Pincemail J, Meziane S. On the Potential Role of the Antioxidant Couple Vitamin E/Selenium Taken by the Oral Route in Skin and Hair Health. Antioxidants (Basel) 2022; 11:2270. [PMID: 36421456 PMCID: PMC9686906 DOI: 10.3390/antiox11112270] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 11/03/2022] [Accepted: 11/09/2022] [Indexed: 09/29/2023] Open
Abstract
The relationship between oxidative stress and skin aging/disorders is well established. Many topical and oral antioxidants (vitamins C and E, carotenoids, polyphenols) have been proposed to protect the skin against the deleterious effect induced by increased reactive oxygen species production, particularly in the context of sun exposure. In this review, we focused on the combination of vitamin E and selenium taken in supplements since both molecules act in synergy either by non-enzymatic and enzymatic pathways to eliminate skin lipids peroxides, which are strongly implicated in skin and hair disorders.
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Affiliation(s)
- Joël Pincemail
- CHU of Liège, Platform Antioxidant Nutrition and Health, Pathology Tower, 4130, Sart Tilman, 4000 Liège, Belgium
| | - Smail Meziane
- Institut Européen des Antioxydants, 54000 Nancy, France
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32
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Azahar A, Mohd Yusof AN, Azhar ZI. A Preliminary Study to Explore the Informed Consent Approach and the Ethical Challenges in the Malaysian Biobanking for Research. Asian Bioeth Rev 2022; 15:141-154. [PMID: 37035484 PMCID: PMC10076458 DOI: 10.1007/s41649-022-00229-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 10/10/2022] [Accepted: 10/11/2022] [Indexed: 11/10/2022] Open
Abstract
Abstract
Since 2005, Malaysia has established several biobanks to keep in line with the advancement of biomedical research and development of biobanks in other countries such as the UK and the USA. Despite the establishment of several biobanks in Malaysia, little is known about the informed consent approach in biobanking research and its ethical challenges. This study aims to identify the approach in obtaining informed consent in the Malaysian biobanking for research and explore its ethical challenges. Using non-probability purposive sampling, an in-depth interview with the key informants was conducted in Klang Valley. Based on the interviews, broad consent is the main approach used in obtaining informed consent in biobanking for research in Malaysia and five major ethical challenges were identified. These challenges include the informants’ opinion on the current informed consent approach, understanding participants’ rights, the role of the research ethics committee, biobanking governance in Malaysia, and informants’ knowledge and awareness. In summary, there is a lack of understanding among those involved in biobanking on the ethical, legal, and social aspects of biobanking for research in Malaysia.
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Affiliation(s)
- Amnah Azahar
- Faculty of Medicine, Department of Medical Ethics and Law, Universiti Teknologi MARA, Sungai Buloh, Malaysia
| | - Aimi Nadia Mohd Yusof
- Faculty of Medicine, Department of Medical Ethics and Law, Universiti Teknologi MARA, Sungai Buloh, Malaysia
| | - Zahir Izuan Azhar
- Faculty of Medicine, Department of Public Health Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia
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Sakamaki-Ching S, Schick S, Grigorean G, Li J, Talbot P. Dermal thirdhand smoke exposure induces oxidative damage, initiates skin inflammatory markers, and adversely alters the human plasma proteome. EBioMedicine 2022; 84:104256. [PMID: 36137411 PMCID: PMC9494172 DOI: 10.1016/j.ebiom.2022.104256] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 07/16/2022] [Accepted: 08/22/2022] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND Thirdhand smoke (THS) exposure correlated with significant metabolism of carcinogenic chemicals and the potential to cause detrimental health effects. Human harm research of THS exposure is limited to one other study and overall, there is a general lack of knowledge of the human health responses to THS exposure. METHODS This was a clinical investigation to evaluate the health effects of 3-h dermal THS exposure from urine and plasma. 10 healthy, non-smoking subjects were recruited for dermal exposure for 3 h exposed to clothing impregnated with filtered clean air or THS. Exposures to clean air or THS occurred 20-30 days apart. FINDINGS In THS-exposed group, there was a significant elevation of urinary 8-OHdG, 8-isoprostane, protein carbonyls. The THS 3-h exposure identified proteomics pathways of inflammatory response (p=2.18 × 10-8), adhesion of blood cells (p=2.23 × 10-8), atherosclerosis (p=2.78 × 10-9), and lichen planus (p=1.77 × 10-8). Nine canonical pathways were significantly activated including leukocyte extravasation signaling (z-score=3.0), and production of nitric oxide and reactive oxygen in macrophages (z-score=2.1). The THS 22-h proteomics pathways revealed inflammation of organ (p=3.09 × 10-8), keratinization of the epidermis (p=4.0 × 10-7), plaque psoriasis (p=5.31 × 10-7), and dermatitis (p=6.0 × 10-7). Two activated canonical pathways were production of nitric oxide and reactive oxygen in macrophages (z-score=2.646), and IL-8 signaling (z-score=2.0). INTERPRETATION This is a clinical study demonstrating that acute dermal exposure to THS mimics the harmful effects of cigarette smoking, alters the human plasma proteome, initiates mechanisms of skin inflammatory disease, and elevates urinary biomarkers of oxidative harm. FUNDING Funding was provided by the Tobacco Related Disease Research Program (TRDRP) 24RT-0037 TRDRP, 24RT-0039 TRDRP, and 28PT-0081 TRDRP.
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Affiliation(s)
- Shane Sakamaki-Ching
- Department of Molecular, Cell, and Systems Biology, University of California, Riverside, United States
| | - Suzaynn Schick
- Center for Tobacco Control Research and Education, University of California, San Francisco, United States
| | - Gabriela Grigorean
- Proteomics Core Facility, University of California, Davis, United States
| | - Jun Li
- Department of Statistics, University of California, Riverside, United States
| | - Prue Talbot
- Department of Molecular, Cell, and Systems Biology, University of California, Riverside, United States.
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Ma Y, Akiyama I. Mechanical force induced DNA double-strand breaks: Ultrasound. Enzymes 2022; 51:53-63. [PMID: 36336408 DOI: 10.1016/bs.enz.2022.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Since the application of ultrasound for clinical diagnosis and therapeutic purposes has been increased rapidly, the effects of exposure to ultrasound on DNA molecules were studied. In this chapter, we introduced various effects of DNA damages caused by different conditions of exposure of ultrasound. Ultrasound with different sound pressure and pulse transmission conditions have been applied in our study. We discussed the threshold of sound pressure of ultrasound-induced DNA damages. Different kinds of pulses of ultrasound and microbubbles' influences on DNA double-strand breaks were also shown.
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Affiliation(s)
- Yue Ma
- Faculty of Life and Medical Science, Doshisha University, Kyotanabe, Japan; Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
| | - Iwaki Akiyama
- Faculty of Life and Medical Science, Doshisha University, Kyotanabe, Japan
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Miyahara R, Taniguchi Y. Selective Unnatural Base Pairing and Recognition of 2-Hydroxy-2'-deoxyadenosine in DNA Using Pseudo-dC Derivatives. J Am Chem Soc 2022; 144:16150-16156. [PMID: 36001794 DOI: 10.1021/jacs.2c07000] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
The formation of unnatural base pairs within duplex DNA would facilitate DNA nanotechnology and biotechnology. Iso-2'-deoxyguanosine (iso-dG) forms base pairs with iso-2'-deoxycytidine, and its use as an unnatural base pair was investigated. Iso-dG is one of the tautomers of 2-hydroxy-2'-deoxyadenosine (2-OH-dA), known as an oxidatively damaged nucleobase, and its selective recognition in DNA plays an important role in the diagnosis and pathogenesis of disease. Therefore, we focused on pseudo-dC (ψdC) as a suitable molecule that recognizes 2-OH-dA in DNA. Since 2-OH-dA shows tautomeric structures in DNA, we designed and used ψdC, which also has a tautomeric structure. We successfully synthesized a ψdC phosphoramidite compound for the synthesis of oligonucleotides (ODNs) as well as its triphosphate derivative (ψdCTP). Tm measurements revealed that ODNs including ψdC showed stable base pair formation with ODNs having 2-OH-dA. In contrast, low Tm values were observed for other bases (dG, dA, dC, and T). The results obtained for the single-nucleotide primer extension reaction revealed that ψdCTP was incorporated into the complementary position of 2-OH-dA in template DNA with high selectivity. In addition, the primer elongation reaction was confirmed to proceed in the presence of dNTPs. The present study reports an artificial nucleic acid that selectively and stably forms unnatural base pairs with 2-OH-dA in DNA.
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Affiliation(s)
- Ryo Miyahara
- Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka 812-8582, Japan
| | - Yosuke Taniguchi
- Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka 812-8582, Japan
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Hu M, Wang Q, Liu B, Ma Q, Zhang T, Huang T, Lv Z, Wang R. Chronic Kidney Disease and Cancer: Inter-Relationships and Mechanisms. Front Cell Dev Biol 2022; 10:868715. [PMID: 35663394 PMCID: PMC9158340 DOI: 10.3389/fcell.2022.868715] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 04/26/2022] [Indexed: 12/20/2022] Open
Abstract
Chronic kidney disease (CKD) has been recognized as an increasingly serious public health problem globally over the decades. Accumulating evidence has shown that the incidence rate of cancer was relatively higher in CKD patients than that in general population, which, mechanistically, may be related to chronic inflammation, accumulation of carcinogenic compounds, oxidative stress, impairment of DNA repair, excessive parathyroid hormone and changes in intestinal microbiota, etc. And in patients with cancer, regardless of tumor types or anticancer treatment, it has been indicated that the morbidity and incidence rate of concomitant CKD was also increased, suggesting a complex inter-relationship between CKD and cancer and arousing increasing attention from both nephrologists and oncologists. This narrative review focused on the correlation between CKD and cancer, and underlying molecular mechanisms, which might provide an overview of novel interdisciplinary research interests and the potential challenges related to the screening and treatment of CKD and cancer. A better understanding of this field might be of help for both nephrologists and oncologists in the clinical practice.
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Affiliation(s)
- Mengsi Hu
- Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Qianhui Wang
- Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Bing Liu
- Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Qiqi Ma
- Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Tingwei Zhang
- Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Tongtong Huang
- Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Zhimei Lv
- Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Rong Wang
- Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
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Molecular allocation of PC4s provides implications for deciphering thermal response in Zhikong scallop (Chlamys farreri). Gene 2022; 818:146216. [PMID: 35093447 DOI: 10.1016/j.gene.2022.146216] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 10/04/2021] [Accepted: 01/13/2022] [Indexed: 12/15/2022]
Abstract
The increasing sea temperature caused by global warming has led to serious death of Zhikong scallop (Chlamys farreri) and improving its thermal tolerance has become an active research area in scallop aquaculture industry. Gene transcriptional coactivator p15 (PC4) plays pivotally multi-faced roles in most vertebrates and some invertebrates, but the systematic identification and characterization of PC4 genes have less been reported in scallops. In this study, 15 PC4 genes (CfPC4s) were identified in Zhikong scallop through whole-genome scanning, including two pairs of tandem duplicate genes located in the same scaffold (CF-19495.9 and CF-19495.10, CF-6819.1 and CF-6819.2). Protein structural and phylogenetic analyses were performed to verify identities and evolutionary relationships of these genes. Spatiotemporal expression patterns were determined at different development stages and in healthy adult tissues, as well as expression regulations in selected tissues (mantles, gills, hemocytes and hearts) after high temperatures challenge (27 °C) with different durations (3 h, 6 h, 12 h, 24 h, 3 d, 6 d, 15 d and 30 d). Spatiotemporal expressions of CfPC4s were ubiquitous but exhibited different patterns, suggesting the functional roles of CfPC4s in all stages of growth and development of the scallop. Expression regulations of CfPC4s and their functional related factors (TFIIA, TFIID, TFIIH and RNAPII) in pre-initiation complex (PIC) in various tissues displayed up- and/or down-regulated responses at different time points, showing time- and/or tissue-dependent expression patterns with function allocation upon different thermal durations. Collectively, this study demonstrated that gene allocation of CfPC4s provided implications for deciphering thermal response in Zhikong scallop and potentially helped in developing strategies for long-term healthy sustainable Zhikong scallop culture.
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Ghosh A, Das C, Ghose S, Maitra A, Roy B, Majumder PP, Biswas NK. Integrative analysis of genomic and transcriptomic data of normal, tumour and co-occurring leukoplakia tissue triads drawn from patients with gingivobuccal oral cancer identifies signatures of tumour initiation and progression. J Pathol 2022; 257:593-606. [PMID: 35358331 PMCID: PMC9545831 DOI: 10.1002/path.5900] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 03/25/2022] [Accepted: 03/28/2022] [Indexed: 11/16/2022]
Abstract
A thickened, white patch — leukoplakia — in the oral cavity is usually benign, but sometimes (in ~9% of individuals) it progresses to malignant tumour. Because the genomic basis of this progression is poorly understood, we undertook this study and collected samples of four tissues — leukoplakia, tumour, adjacent normal, and blood — from each of 28 patients suffering from gingivobuccal oral cancer. We performed multiomics analysis of the 112 collected tissues (four tissues per patient from 28 patients) and integrated information on progressive changes in the mutational and transcriptional profiles of each patient to create this genomic narrative. Additionally, we generated and analysed whole‐exome sequence data from leukoplakia tissues collected from 11 individuals not suffering from oral cancer. Nonsynonymous somatic mutations in the CASP8 gene were identified as the likely events to initiate malignant transformation, since these were frequently shared between tumour and co‐occurring leukoplakia. CASP8 alterations were also shown to enhance expressions of genes that favour lateral spread of mutant cells. During malignant transformation, additional pathogenic mutations are acquired in key genes (TP53, NOTCH1, HRAS) (41% of patients); chromosomal‐instability (arm‐level deletions of 19p and q, focal‐deletion of DNA‐repair pathway genes and NOTCH1, amplification of EGFR) (77%), and increased APOBEC‐activity (23%) are also observed. These additional alterations were present singly (18% of patients) or in combination (68%). Some of these alterations likely impact immune‐dynamics of the evolving transformed tissue; progression to malignancy is associated with immune suppression through infiltration of regulatory T‐cells (56%), depletion of cytotoxic T‐cells (68%), and antigen‐presenting dendritic cells (72%), with a concomitant increase in inflammation (92%). Patients can be grouped into three clusters by the estimated time to development of cancer from precancer by acquiring additional mutations (range: 4–10 years). Our findings provide deep molecular insights into the evolutionary processes and trajectories of oral cancer initiation and progression. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Affiliation(s)
- Arnab Ghosh
- National Institute of Biomedical Genomics, Kalyani, India
| | | | - Sandip Ghose
- Dr. R. Ahmed Dental College and Hospital, Kolkata, India
| | - Arindam Maitra
- National Institute of Biomedical Genomics, Kalyani, India
| | - Bidyut Roy
- Indian Statistical Institute, Kolkata, India
| | - Partha P Majumder
- National Institute of Biomedical Genomics, Kalyani, India.,Indian Statistical Institute, Kolkata, India
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Kanakoglou DS, Pampalou A, Vrachnos DM, Karatrasoglou EA, Zouki DN, Dimonitsas E, Klonou A, Kokla G, Theologi V, Christofidou E, Sakellariou S, Lakiotaki E, Piperi C, Korkolopoulou P. Laying the groundwork for the Biobank of Rare Malignant Neoplasms at the service of the Hellenic Network of Precision Medicine on Cancer. Int J Oncol 2022; 60:31. [PMID: 35169862 PMCID: PMC8878762 DOI: 10.3892/ijo.2022.5321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Accepted: 12/23/2021] [Indexed: 11/06/2022] Open
Abstract
Biobanks constitute an integral part of precision medicine. They provide a repository of biospecimens that may be used to elucidate the pathophysiology, support diagnoses, and guide the treatment of diseases. The pilot biobank of rare malignant neoplasms has been established in the context of the Hellenic Network of Precision Medicine on Cancer and aims to enhance future clinical and/or research studies in Greece by collecting, processing, and storing rare malignant neoplasm samples with associated data. The biobank currently comprises 553 samples; 384 samples of hematopoietic and lymphoid tissue malignancies, 72 samples of pediatric brain tumors and 97 samples of malignant skin neoplasms. In this article, sample collections and their individual significance in clinical research are described in detail along with computational methods developed specifically for this project. A concise review of the Greek biobanking landscape is also delineated, in addition to recommended technologies, methodologies and protocols that were integrated during the creation of the biobank. This project is expected to re‑enforce current clinical and research studies, introduce advances in clinical and genetic research and potentially aid in future targeted drug discovery. It is our belief that the future of medical research is entwined with accessible, effective, and ethical biobanking and that our project will facilitate research planning in the '‑omic' era by contributing high‑quality samples along with their associated data.
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Affiliation(s)
- Dimitrios S. Kanakoglou
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Andromachi Pampalou
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Dimitrios M. Vrachnos
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Eleni A. Karatrasoglou
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Dionysia N. Zouki
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Emmanouil Dimonitsas
- Department of Plastic and Reconstructive Surgery, Greek Anticancer Institute, Saint Savvas Hospital, 11522 Athens, Greece
| | - Alexia Klonou
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Georgia Kokla
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Varvara Theologi
- Department of Pathology, Andreas Syggros Hospital of Cutaneous and Venereal Diseases, 16121 Athens, Greece
| | - Errieta Christofidou
- Department of Pathology, Andreas Syggros Hospital of Cutaneous and Venereal Diseases, 16121 Athens, Greece
| | - Stratigoula Sakellariou
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Eleftheria Lakiotaki
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Christina Piperi
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Penelope Korkolopoulou
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
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Fedeli P, Scendoni R, Cingolani M, Corrales Compagnucci M, Cirocchi R, Cannovo N. Informed Consent and Protection of Personal Data in Genetic Research on COVID-19. Healthcare (Basel) 2022; 10:healthcare10020349. [PMID: 35206963 PMCID: PMC8871888 DOI: 10.3390/healthcare10020349] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 01/17/2022] [Accepted: 02/09/2022] [Indexed: 11/16/2022] Open
Abstract
The particular characteristics of COVID-19 demand the careful biomedical study of samples from patients who have shown different symptomatology, in order to understand the genetic foundations of its phenotypic expression. Research on genetic material from COVID-19 patients is indispensable for understanding the biological bases for its varied clinical manifestations. The issue of “informed consent” constitutes the crux of the problem in regulating research biobanks, because it concerns the relationship between the person and the parts separated from the body. There are several consensus models that can be adopted, varying from quite restricted models of specific informed consent to forms that allow very broad authorization (open consent). Our current understanding of COVID-19 is incomplete. Thus, we cannot plan, with precision, the research to be conducted on biological samples that have been, or will be, collected from patients infected by the novel coronavirus. Therefore, we suggest utilizing the “participation pact” between researchers and donors, based on a new form of participation in research, which offers a choice based on the principles of solidarity and reciprocity, which represent the communication of “values”. In the last part of this paper, the general data protection regulation concerning the matter is discussed. The treatment of personal data must be performed with explicit goals, and donors must be provided with a clear, transparent explanation of the methods, goals and time of storage. The data must not be provided to unauthorized subjects. In conclusion, open informed consent forms will be necessary for research on individual patients and on populations.
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Affiliation(s)
| | - Roberto Scendoni
- Department of Law, University of Macerata, 62100 Macerata, Italy;
| | - Mariano Cingolani
- Department of Law, University of Macerata, 62100 Macerata, Italy;
- Correspondence:
| | - Marcelo Corrales Compagnucci
- Centre for Advanced Studies on Biomedical Innovation Law (CeBIL), Faculty of Law, University of Copenhagen, Karen Blixens Plads 16, DK-2300 Copenhagen, Denmark;
| | - Roberto Cirocchi
- Department of Surgical and Biomedical Sciences, University of Perugia, 06132 Perugia, Italy;
| | - Nunzia Cannovo
- Ethic Committee, University of Naples, 80138 Napoli, Italy;
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Chen KC, Tsai SW, Shie RH, Zeng C, Yang HY. Indoor Air Pollution Increases the Risk of Lung Cancer. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19031164. [PMID: 35162188 PMCID: PMC8834322 DOI: 10.3390/ijerph19031164] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 01/07/2022] [Accepted: 01/14/2022] [Indexed: 02/04/2023]
Abstract
(1) Background: Cooking and burning incense are important sources of indoor air pollutants. No studies have provided biological evidence of air pollutants in the lungs to support this association. Analysis of pleural fluid may be used to measure the internal exposure dose of air pollutants in the lung. The objective of this study was to provide biological evidence of indoor air pollutants and estimate their risk of lung cancer. (2) Methods: We analyzed 14 common air pollutants in the pleural fluid of 39 cases of lung adenocarcinoma and 40 nonmalignant controls by gas chromatography-mass spectrometry. (3) Results: When we excluded the current smokers and adjusted for age, the adjusted odds ratios (ORs) were 2.22 (95% confidence interval CI = 0.77-6.44) for habitual cooking at home and 3.05 (95% CI = 1.06-8.84) for indoor incense burning. In females, the adjusted ORs were 5.39 (95% CI = 1.11-26.20) for habitual cooking at home and 6.01 (95% CI = 1.14-31.66) for indoor incense burning. In pleural fluid, the most important exposure biomarkers for lung cancer were naphthalene, ethylbenzene, and o-xylene. (4) Conclusions: Habitual cooking and indoor incense burning increased the risk of lung adenocarcinoma.
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Affiliation(s)
- Ke-Cheng Chen
- Division of Thoracic Surgery, Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan;
- Department of Surgery, National Taiwan University College of Medicine, Taipei 100, Taiwan
| | - Shih-Wei Tsai
- Institute of Environmental and Occupational Health Sciences, National Taiwan University College of Public Health, Taipei 10055, Taiwan;
- Department of Public Health, National Taiwan University College of Public Health, Taipei 10055, Taiwan
| | - Ruei-Hao Shie
- Green Energy & Environmental Research Laboratories, Industrial Technology Research Institute, Hsinchu 31040, Taiwan;
| | - Chian Zeng
- Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei 10055, Taiwan;
| | - Hsiao-Yu Yang
- Institute of Environmental and Occupational Health Sciences, National Taiwan University College of Public Health, Taipei 10055, Taiwan;
- Department of Public Health, National Taiwan University College of Public Health, Taipei 10055, Taiwan
- Department of Environmental and Occupational Medicine, National Taiwan University Hospital, Taipei 100, Taiwan
- Correspondence: ; Tel.: +886-2-3366-8102
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Kopylova OV, Ershova AI, Pokrovskaya MS, Meshkov AN, Efimova IA, Serebryanskaya ZZ, Blokhina AV, Borisova AL, Kondratskaya VA, Limonova AS, Smetnev SА, Skirko OP, Shalnova SА, Metelskaya VA, Kontsevaya AV, Drapkina OM. Population-nosological research biobank of the National Medical Research Center for Therapy and Preventive Medicine: analysis of biosamples, principles of collecting and storing information. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2022. [DOI: 10.15829/1728-8800-2021-3119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Aim. To analyze the structure of clinical data, as well as the principles of collecting and storing related data of the biobank of the National Medical Research Center for Therapy and Preventive Medicine (hereinafter Biobank).Material and methods. The analysis was carried out using the documentation available in the Biobank, as well as the databases used in its work. The paper presents clinical data on biosamples available in the Biobank as of August 18, 2021.Results. At the time of analysis, the Biobank had 373547 samples collected from 54192 patients within 37 research projects. The article presents the analysis of data representation and quantitative assessment of the presence/absence of common diagnoses in clinical projects. Approaches to documenting clinical information associated with biological samples stored in the Biobank were assessed. The methods and tools used for standardization and automation of processes used in the Biobank were substantiated.Conclusion. The Biobank of the National Medical Research Center for Therapy and Preventive Medicine is the largest research biobank in Russia, which meets all modern international requirements and is one of the key structures that improve the research quality and intensify their conduct both within the one center and in cooperation with other biobanks and scientific institutions. The collection and systematic storage of clinical abstracts of biological samples is an integral and most important part of the Biobank’s work.
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Affiliation(s)
- O. V. Kopylova
- National Medical Research Center for Therapy and Preventive Medicine
| | - A. I. Ershova
- National Medical Research Center for Therapy and Preventive Medicine
| | - M. S. Pokrovskaya
- National Medical Research Center for Therapy and Preventive Medicine
| | - A. N. Meshkov
- National Medical Research Center for Therapy and Preventive Medicine
| | - I. A. Efimova
- National Medical Research Center for Therapy and Preventive Medicine
| | | | - A. V. Blokhina
- National Medical Research Center for Therapy and Preventive Medicine
| | - A. L. Borisova
- National Medical Research Center for Therapy and Preventive Medicine
| | | | - A. S. Limonova
- National Medical Research Center for Therapy and Preventive Medicine
| | - S. А. Smetnev
- National Medical Research Center for Therapy and Preventive Medicine
| | - O. P. Skirko
- National Medical Research Center for Therapy and Preventive Medicine
| | - S. А. Shalnova
- National Medical Research Center for Therapy and Preventive Medicine
| | - V. A. Metelskaya
- National Medical Research Center for Therapy and Preventive Medicine
| | | | - O. M. Drapkina
- National Medical Research Center for Therapy and Preventive Medicine
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Umpeleva TV, Vakhrusheva DV, Skornyakov SN. Biobank as a key component of supporting research in phthisiology and infectious diseases. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2022. [DOI: 10.15829/1728-8800-2021-3084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Conducting fundamental and clinical research in the field of tuberculosis is an important step towards reducing related morbidity and mortality, but access to a sufficient number of high-quality samples required for research is an unsolved problem in Russia. This review is devoted to biobanking as a key component of modern research in personalized medicine, as well as to the status and prospects for developing this area in phthisiology and infectious diseases combined with tuberculosis.
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Affiliation(s)
- T. V. Umpeleva
- National Medical Research Center of Phthisiopulmonology and Infectious Diseases
| | - D. V. Vakhrusheva
- National Medical Research Center of Phthisiopulmonology and Infectious Diseases
| | - S. N. Skornyakov
- National Medical Research Center of Phthisiopulmonology and Infectious Diseases
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Li D, Yan L, Lin F, Yuan X, Yang X, Yang X, Wei L, Yang Y, Lu Y. Urinary Biomarkers for the Noninvasive Detection of Gastric Cancer. J Gastric Cancer 2022; 22:306-318. [DOI: 10.5230/jgc.2022.22.e28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 08/01/2022] [Accepted: 08/16/2022] [Indexed: 12/24/2022] Open
Affiliation(s)
- Dehong Li
- Gansu Provincial Clinical Research Center for Laboratory Medicine, Lanzhou, China
- Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, China
| | - Li Yan
- Gansu Provincial Clinical Research Center for Laboratory Medicine, Lanzhou, China
- Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, China
| | - Fugui Lin
- Gansu Provincial Clinical Research Center for Laboratory Medicine, Lanzhou, China
- Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, China
| | - Xiumei Yuan
- Gansu Provincial Clinical Research Center for Laboratory Medicine, Lanzhou, China
- Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, China
| | - Xingwen Yang
- Gansu Provincial Clinical Research Center for Laboratory Medicine, Lanzhou, China
- Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, China
| | - Xiaoyan Yang
- Gansu Provincial Clinical Research Center for Laboratory Medicine, Lanzhou, China
- Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, China
| | - Lianhua Wei
- Gansu Provincial Clinical Research Center for Laboratory Medicine, Lanzhou, China
- Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, China
| | - Yang Yang
- Gansu Provincial Clinical Research Center for Laboratory Medicine, Lanzhou, China
- Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, China
| | - Yan Lu
- Gansu Provincial Clinical Research Center for Laboratory Medicine, Lanzhou, China
- Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, China
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Piergentili I, Bouwmans PR, Reinalda L, Lewis RW, Klemm B, Liu H, de Kruijff RM, Denkova AG, Eelkema R. Thioanisole ester based logic gate cascade to control ROS-triggered micellar degradation. Polym Chem 2022; 13:2383-2390. [PMID: 35664499 PMCID: PMC9016795 DOI: 10.1039/d2py00207h] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 03/29/2022] [Indexed: 12/11/2022]
Abstract
Thioanisole ester polymer side chains hydrolyze exclusively upon thioether oxidation, showing logic gate response. ROS-induced ester hydrolysis on the hydrophobic domain leads to nanocarrier disassembly with potential for targeted drug release.
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Affiliation(s)
- Irene Piergentili
- Delft University of Technology, Department of Chemical Engineering, Van der Maasweg 9, 2629 HZ Delft, The Netherlands
| | - Pepijn R. Bouwmans
- Delft University of Technology, Department of Chemical Engineering, Van der Maasweg 9, 2629 HZ Delft, The Netherlands
| | - Luuk Reinalda
- Delft University of Technology, Department of Chemical Engineering, Van der Maasweg 9, 2629 HZ Delft, The Netherlands
| | - Reece W. Lewis
- Delft University of Technology, Department of Chemical Engineering, Van der Maasweg 9, 2629 HZ Delft, The Netherlands
| | - Benjamin Klemm
- Delft University of Technology, Department of Chemical Engineering, Van der Maasweg 9, 2629 HZ Delft, The Netherlands
| | - Huanhuan Liu
- Delft University of Technology, Department of Radiation Science and Technology, Mekelweg 15, 2629 JB Delft, The Netherlands
| | - Robin M. de Kruijff
- Delft University of Technology, Department of Radiation Science and Technology, Mekelweg 15, 2629 JB Delft, The Netherlands
| | - Antonia G. Denkova
- Delft University of Technology, Department of Radiation Science and Technology, Mekelweg 15, 2629 JB Delft, The Netherlands
| | - Rienk Eelkema
- Delft University of Technology, Department of Chemical Engineering, Van der Maasweg 9, 2629 HZ Delft, The Netherlands
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Ožvald I, Božičević D, Duh L, Vinković Vrček I, Pavičić I, Domijan AM, Milić M. Effects of a 3-Week Hospital-Controlled Very-Low-Calorie Diet in Severely Obese Patients. Nutrients 2021; 13:4468. [PMID: 34960018 PMCID: PMC8703721 DOI: 10.3390/nu13124468] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/10/2021] [Accepted: 12/11/2021] [Indexed: 11/28/2022] Open
Abstract
Although a very-low-calorie diet (VLCD) is considered safe and has demonstrated benefits among other types of diets, data are scarce concerning its effects on improving health and weight loss in severely obese patients. As part of the personalized weight loss program developed at the Duga Resa Special Hospital for Extended Treatment, Croatia, we evaluated anthropometric, biochemical, and permanent DNA damage parameters (assessed with the cytochalasin B-blocked micronucleus cytome assay-CBMN) in severely obese patients (BMI ≥ 35 kg m-2) after 3-weeks on a 567 kcal, hospital-controlled VLCD. This is the first study on the permanent genomic (in)stability in such VLCD patients. VLCDs caused significant decreases in weight (loss), parameters of the lipid profile, urea, insulin resistance, and reduced glutathione (GSH). Genomic instability parameters were lowered by half, reaching reference values usually found in the healthy population. A correlation was found between GSH decrease and reduced DNA damage. VLCDs revealed susceptible individuals with remaining higher DNA damage for further monitoring. In a highly heterogeneous group (class II and III in obesity, differences in weight, BMI, and other categories) consisting of 26 obese patients, the approach demonstrated its usefulness and benefits in health improvement, enabling an individual approach to further monitoring, diagnosis, treatment, and risk assessment based on changing anthropometric/biochemical VLCD parameters, and CBMN results.
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Affiliation(s)
- Ivan Ožvald
- Duga Resa Special Hospital for Extended Treatment, 47250 Duga Resa, Croatia; (I.O.); (D.B.); (L.D.)
| | - Dragan Božičević
- Duga Resa Special Hospital for Extended Treatment, 47250 Duga Resa, Croatia; (I.O.); (D.B.); (L.D.)
| | - Lidija Duh
- Duga Resa Special Hospital for Extended Treatment, 47250 Duga Resa, Croatia; (I.O.); (D.B.); (L.D.)
| | - Ivana Vinković Vrček
- Analytical Toxicology and Mineral Metabolism Unit, Institute for Medical Research and Occupational Health (IMROH), Ksaverska Cesta 2, 10001 Zagreb, Croatia;
| | - Ivan Pavičić
- Radiation Dosimetry and Radiobiology Unit, Institute for Medical Research and Occupational Health (IMROH), Ksaverska Cesta 2, 10001 Zagreb, Croatia;
| | - Ana-Marija Domijan
- Department of Pharmaceutical Botany, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia;
| | - Mirta Milić
- Mutagenesis Unit, Institute for Medical Research and Occupational Health (IMROH), Ksaverska Cesta 2, 10001 Zagreb, Croatia
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Tyagi A, Haq S, Ramakrishna S. Redox regulation of DUBs and its therapeutic implications in cancer. Redox Biol 2021; 48:102194. [PMID: 34814083 PMCID: PMC8608616 DOI: 10.1016/j.redox.2021.102194] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 11/19/2021] [Indexed: 02/06/2023] Open
Abstract
Reactive oxygen species (ROS) act as a double-edged sword in cancer, where low levels of ROS are beneficial but excessive accumulation leads to cancer progression. Elevated levels of ROS in cancer are counteracted by the antioxidant defense system. An imbalance between ROS generation and the antioxidant system alters gene expression and cellular signaling, leading to cancer progression or death. Post-translational modifications, such as ubiquitination, phosphorylation, and SUMOylation, play a critical role in the maintenance of ROS homeostasis by controlling ROS production and clearance. Recent evidence suggests that deubiquitinating enzymes (DUBs)-mediated ubiquitin removal from substrates is regulated by ROS. ROS-mediated oxidation of the catalytic cysteine (Cys) of DUBs, leading to their reversible inactivation, has emerged as a key mechanism regulating DUB-controlled cellular events. A better understanding of the mechanism by which DUBs are susceptible to ROS and exploring the ways to utilize ROS to pharmacologically modulate DUB-mediated signaling pathways might provide new insight for anticancer therapeutics. This review assesses the recent findings regarding ROS-mediated signaling in cancers, emphasizes DUB regulation by oxidation, highlights the relevant recent findings, and proposes directions of future research based on the ROS-induced modifications of DUB activity.
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Affiliation(s)
- Apoorvi Tyagi
- Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, 04763, South Korea
| | - Saba Haq
- Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, 04763, South Korea
| | - Suresh Ramakrishna
- Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, 04763, South Korea; College of Medicine, Hanyang University, Seoul, 04763, South Korea.
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48
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Wen JX, Tong YL, Ma X, Wang RL, Li RS, Song HT, Zhao YL. Therapeutic effects and potential mechanism of dehydroevodiamine on N-methyl-N'-nitro-N-nitrosoguanidine-induced chronic atrophic gastritis. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 91:153619. [PMID: 34320422 DOI: 10.1016/j.phymed.2021.153619] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 04/27/2021] [Accepted: 05/28/2021] [Indexed: 06/13/2023]
Abstract
BACKGROUNDS Dehydroevodiamine (DHE) is a quinazoline alkaloid isolated from a Chinese herbal medicine, named Euodiae Fructus (Wu-Zhu-Yu in Chinese). This study aimed to investigate the therapeutic effects and potential mechanism of DHE on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced chronic atrophic gastritis (CAG) based on integrated approaches. METHODS Therapeutic effects of DHE on serum biochemical indices and histopathology of gastric tissue in MNNG-induced CAG rats were analyzed. MNNG-induced GES-1 human gastric epithelial cell injury model was established. Cell viability and proliferation was quantified by a cell counting kit-8 assay. Cell morphology and mitochondrial membrane potential (MMP) were detected by a high content screening (HCS) assay. Cell migration and invasion were detected by a Transwell chamber. Moreover, UHPLC-Q-TOF/MS was performed to investigate the potential metabolites and signaling pathway affecting the protective effects of DHE on MNNG-induced cell migration and invasion of GES-1. Furthermore, in view of the key role of angiogenesis in the transformation of inflammation and cancer, this study explored relative mRNA and protein expression levels of HIF-1α-mediated VEGF pathway in vivo and in vitro by RT-PCR and Western Blotting, respectively. RESULTS The results showed that the therapeutic effects of DHE on CAG rats were presented in down-regulation serum biochemical indices and alleviating histological damage of gastric tissue. Besides, DHE has an effect on increasing cell proliferation of GES-1 cells, ameliorating MNNG-induced gastric epithelial cell damage and mitochondrial dysfunction. In addition, DHE could inhibit MNNG induced migration and invasion of GES-1 cells. Cell metabolomics analyses showed that the protective effect of DHE on GES-1 cells is mainly associated with the regulation of inflammation metabolites and energy metabolism related pathways. It was found that DHE has a regulating effect on tumor angiogenesis and can inhibit the relative gene and protein expression of HIF-1α-mediated VEGF signaling pathway. CONCLUSIONS The present work highlighted the role of DHE ameliorated gastric injury in MNNG-induced CAG rats in vivo and GES-1 cell migration in vitro by inhibiting HIF-1α/VEGF angiogenesis pathway. These results suggest that DHE may be the effective components of Euodiae Fructus, which provides a new agent for the treatment of CAG.
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Affiliation(s)
- Jian-Xia Wen
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
| | - Yu-Ling Tong
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
| | - Xiao Ma
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Rui-Lin Wang
- Department of Integrative Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Rui-Sheng Li
- Research Center for Clinical and Translational Medicine, Chinese PLA General Hospital, Beijing, China
| | - Hong-Tao Song
- Department of Pharmacy, 900 Hospital of the Joint Logistics Team, Fuzhou, China.
| | - Yan-Ling Zhao
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China.
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Misak A, Brezova V, Chovanec M, Luspai K, Nasim MJ, Grman M, Tomasova L, Jacob C, Ondrias K. EPR Study of KO 2 as a Source of Superoxide and •BMPO-OH/OOH Radical That Cleaves Plasmid DNA and Detects Radical Interaction with H 2S and Se-Derivatives. Antioxidants (Basel) 2021; 10:antiox10081286. [PMID: 34439533 PMCID: PMC8389328 DOI: 10.3390/antiox10081286] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 08/10/2021] [Accepted: 08/11/2021] [Indexed: 11/25/2022] Open
Abstract
Superoxide radical anion (O2•−) and its derivatives regulate numerous physiological and pathological processes, which are extensively studied. The aim of our work was to utilize KO2 as a source of O2•− and the electron paramagnetic resonance (EPR) spin trapping 5-tert-butoxycarbonyl-5-methyl-1-pyrroline N-oxide (BMPO) technique for the preparation of •BMPO-OOH and/or •BMPO-OH radicals in water solution without DMSO. The method distinguishes the interactions of various compounds with •BMPO-OOH and/or •BMPO-OH radicals over time. Here, we show that the addition of a buffered BMPO-HCl mixture to powdered KO2 formed relatively stable •BMPO-OOH and •BMPO-OH radicals and H2O2, where the •BMPO-OOH/OH ratio depended on the pH. At a final pH of ~6.5–8.0, the concentration of •BMPO-OOH radicals was ≥20 times higher than that of •BMPO-OH, whereas at pH 9.0–10.0, the •BMPO-OH radicals prevailed. The •BMPO-OOH/OH radicals effectively cleaved the plasmid DNA. H2S decreased the concentration of •BMPO-OOH/OH radicals, whereas the selenium derivatives 1-methyl-4-(3-(phenylselanyl) propyl) piperazine and 1-methyl-4-(4-(phenylselanyl) butyl) piperazine increased the proportion of •BMPO-OH over the •BMPO-OOH radicals. In conclusion, the presented approach of using KO2 as a source of O2•−/H2O2 and EPR spin trap BMPO for the preparation of •BMPO-OOH/OH radicals in a physiological solution could be useful to study the biological effects of radicals and their interactions with compounds.
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Affiliation(s)
- Anton Misak
- Biomedical Research Center, Department of Molecular Physiology, Institute of Clinical and Translational Research, Slovak Academy of Sciences, Dúbravská Cesta 9, 84505 Bratislava, Slovakia; (A.M.); (M.G.); (L.T.)
| | - Vlasta Brezova
- Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinského 9, 81237 Bratislava, Slovakia; (V.B.); (K.L.)
| | - Miroslav Chovanec
- Biomedical Research Center, Department of Genetics, Cancer Research Institute, Slovak Academy of Sciences, Dúbravská Cesta 9, 84505 Bratislava, Slovakia;
| | - Karol Luspai
- Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinského 9, 81237 Bratislava, Slovakia; (V.B.); (K.L.)
| | - Muhammad Jawad Nasim
- Division of Bioorganic Chemistry, School of Pharmacy, University of Saarland, D-66123 Saarbruecken, Germany; (M.J.N.); (C.J.)
| | - Marian Grman
- Biomedical Research Center, Department of Molecular Physiology, Institute of Clinical and Translational Research, Slovak Academy of Sciences, Dúbravská Cesta 9, 84505 Bratislava, Slovakia; (A.M.); (M.G.); (L.T.)
| | - Lenka Tomasova
- Biomedical Research Center, Department of Molecular Physiology, Institute of Clinical and Translational Research, Slovak Academy of Sciences, Dúbravská Cesta 9, 84505 Bratislava, Slovakia; (A.M.); (M.G.); (L.T.)
| | - Claus Jacob
- Division of Bioorganic Chemistry, School of Pharmacy, University of Saarland, D-66123 Saarbruecken, Germany; (M.J.N.); (C.J.)
| | - Karol Ondrias
- Biomedical Research Center, Department of Molecular Physiology, Institute of Clinical and Translational Research, Slovak Academy of Sciences, Dúbravská Cesta 9, 84505 Bratislava, Slovakia; (A.M.); (M.G.); (L.T.)
- Correspondence:
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50
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Annaratone L, De Palma G, Bonizzi G, Sapino A, Botti G, Berrino E, Mannelli C, Arcella P, Di Martino S, Steffan A, Daidone MG, Canzonieri V, Parodi B, Paradiso AV, Barberis M, Marchiò C. Basic principles of biobanking: from biological samples to precision medicine for patients. Virchows Arch 2021; 479:233-246. [PMID: 34255145 PMCID: PMC8275637 DOI: 10.1007/s00428-021-03151-0] [Citation(s) in RCA: 101] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Revised: 06/24/2021] [Accepted: 06/30/2021] [Indexed: 12/15/2022]
Abstract
The term "biobanking" is often misapplied to any collection of human biological materials (biospecimens) regardless of requirements related to ethical and legal issues or the standardization of different processes involved in tissue collection. A proper definition of biobanks is large collections of biospecimens linked to relevant personal and health information (health records, family history, lifestyle, genetic information) that are held predominantly for use in health and medical research. In addition, the International Organization for Standardization, in illustrating the requirements for biobanking (ISO 20387:2018), stresses the concept of biobanks being legal entities driving the process of acquisition and storage together with some or all of the activities related to collection, preparation, preservation, testing, analysing and distributing defined biological material as well as related information and data. In this review article, we aim to discuss the basic principles of biobanking, spanning from definitions to classification systems, standardization processes and documents, sustainability and ethical and legal requirements. We also deal with emerging specimens that are currently being generated and shaping the so-called next-generation biobanking, and we provide pragmatic examples of cancer-associated biobanking by discussing the process behind the construction of a biobank and the infrastructures supporting the implementation of biobanking in scientific research.
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Affiliation(s)
- Laura Annaratone
- Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy.,Department of Medical Sciences, University of Turin, Turin, Italy
| | - Giuseppe De Palma
- Institutional BioBank, Experimental Oncology and Biobank Management Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy
| | - Giuseppina Bonizzi
- Unit of Histopathology and Molecular Diagnostics, Division of Pathology and Laboratory Medicine, IEO, European Institute of Oncology, IRCCS, Milan, Italy
| | - Anna Sapino
- Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy.,Department of Medical Sciences, University of Turin, Turin, Italy
| | - Gerardo Botti
- Istituto Nazionale Tumori, Fondazione G. Pascale, IRCCS, Naples, Italy
| | - Enrico Berrino
- Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy.,Department of Medical Sciences, University of Turin, Turin, Italy
| | | | - Pamela Arcella
- Department of Oncology, University of Turin, Turin, Italy
| | - Simona Di Martino
- Department of Pathology, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Agostino Steffan
- Immunopathology and Cancer Biomarkers, IRCCS CRO Aviano-National Cancer Institute, Aviano, Italy
| | | | - Vincenzo Canzonieri
- Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.,Pathology Unit, IRCCS CRO Aviano-National Cancer Institute, Aviano, Italy
| | | | - Angelo Virgilio Paradiso
- Institutional BioBank, Experimental Oncology and Biobank Management Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy
| | - Massimo Barberis
- Unit of Histopathology and Molecular Diagnostics, Division of Pathology and Laboratory Medicine, IEO, European Institute of Oncology, IRCCS, Milan, Italy
| | - Caterina Marchiò
- Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy. .,Department of Medical Sciences, University of Turin, Turin, Italy.
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