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Zhang MY, Zhang H, Yao YM, Yang DW. Krüppel-like factors in mitochondrial quality control. Front Physiol 2025; 16:1554877. [PMID: 40265156 PMCID: PMC12011804 DOI: 10.3389/fphys.2025.1554877] [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: 01/14/2025] [Accepted: 03/25/2025] [Indexed: 04/24/2025] Open
Abstract
Krüppel-like factors (KLFs) are a group of transcription factors characterized by conserved zinc finger domains in the C-terminus, which are critically involved in basic cellular processes, including growth, differentiation, apoptosis, and angiogenesis, and play important roles in many pathophysiological responses. Mitochondrial homeostasis relies on a coordinated mitochondrial quality control system, which maintains the number and morphological stability and coordinates mitochondrial physiological functions through renewal and self-clearance. In this paper, we review the current advances of KLFs in mitochondrial quality control (MQC), including the potential roles and regulatory mechanisms in mitochondrial biogenesis, mitochondrial fusion/fission, mitophagy and mitochondrial unfolded protein response. We also introduce the specific pharmacological modulation of KLFs, expecting to transforming basic research achievements and providing the possibility of targeted therapy for KLFs.
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Affiliation(s)
- M. Y. Zhang
- Department of Nephrology, Tianjin Hospital of Tianjin University, Tianjin, China
| | - H. Zhang
- Translational Medicine Research Center, Medical Innovation Research Division and the Fourth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Y. M. Yao
- Translational Medicine Research Center, Medical Innovation Research Division and the Fourth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - D. W. Yang
- Department of Nephrology, Tianjin Hospital of Tianjin University, Tianjin, China
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2
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Kovalevska L, Kalman S, Sushnova A, Malysheva O, Rozumenko V, Malysheva T, Kashuba E. Differential Expression of MRPS18 Family Genes in Brain Tumor Samples. Exp Oncol 2025; 46:368-374. [PMID: 39985348 DOI: 10.15407/exp-oncology.2024.04.368] [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: 02/20/2025] [Indexed: 02/24/2025]
Abstract
BACKGROUND Brain tumors account for 2%-3% of all malignant neoplasms and 85%-90% of all primary tumors of the central nervous system with the 5-year survival rate of 35%. Additional biomarkers could help refine the molecular profile of brain tumors and prognosis of the disease. AIM To study differential expression patterns of the MRPS18 family genes in tumor tissue and the peripheral blood of patients with brain tumors of various types. MATERIALS AND METHODS The total RNA was isolated from blood and tumor tissue samples of 27 patients with brain tumors. The quantitative polymerase chain reaction (qPCR) was performed. Also, immunohistochemical (IHC) studies of the MRPS18 family proteins were performed on deparaffinized tissue sections. RESULTS The MRPS18-1-3 genes were highly expressed at the mRNA level in tumor tissue and the peripheral blood of patients with brain tumors. All 3 genes showed different patterns of expression depending on the tumor type. The highest MRPS18-1 mRNA expression was detected in glioblastoma (GB) samples in both tumor samples and the peripheral blood. In general, MRPS18-1 expression was higher in G4 tumors, compared to G2. MRPS18-3 gene was expressed as higher levels in G2 samples and in embryonic tumors. MRPS18-2 was expressed in all studied samples, with no regard to the tumor grade or type. The MRPS18-2 IHC staining was detected at high levels in most brain tumors. CONCLUSIONS The MRPS18 family genes showed similar patterns of mRNA expression in tissue samples of brain tumors and peripheral blood of patients. The highest levels of MRPS18-1 mRNA were detected in GB samples, while the highest protein signal was detected for MRPS18-2 in almost all brain tumor samples.
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Affiliation(s)
- L Kovalevska
- R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NASU, Kyiv, Ukraine
| | - S Kalman
- R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NASU, Kyiv, Ukraine
| | - A Sushnova
- R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NASU, Kyiv, Ukraine
| | - O Malysheva
- The State Institution A.P. Romodanov Neurosurgery Institute of NAMSU, Kyiv, Ukraine
| | - V Rozumenko
- The State Institution A.P. Romodanov Neurosurgery Institute of NAMSU, Kyiv, Ukraine
| | - T Malysheva
- The State Institution A.P. Romodanov Neurosurgery Institute of NAMSU, Kyiv, Ukraine
| | - E Kashuba
- R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NASU, Kyiv, Ukraine
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3
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Woo J, Ji H, Jeon K, Kim H, Yoon S, Hwang Y, Cho E, Park D, Jung E. Anti-skin aging effects of Gosori liquor lees extract by regulating interactions between senescent fibroblasts and adipose-derived stem cells. Int J Cosmet Sci 2025. [PMID: 39838700 DOI: 10.1111/ics.13046] [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: 05/02/2024] [Revised: 12/13/2024] [Accepted: 12/23/2024] [Indexed: 01/23/2025]
Abstract
When cellular ageing is accelerated by various extrinsic/endogenous stimuli, regenerative function deteriorates, and enriched secretomes, such as the senescence-associated secretory phenotype (SASP), contribute to chronic inflammation and cause matrix degeneration. SASPs from senescent fibroblasts exacerbate cellular senescence via autocrine signalling and also accelerate skin ageing through the induction of neighbouring cell senescence via paracrine signalling. The interaction between dermis fibroblasts and their neighbours, adipose-derived stem cells (ADSCs) in the hypodermis, which lies deep in the dermis, is a potential target for skin ageing. In this study, we observed that an extract of the lees of Gosori liquor (GLE), a traditional Korean liquor made by fermenting millet and rice, suppressed the senescence of fibroblasts, including SASP production, in a replicative senescent model. We further examined whether the anti-ageing effects of GLE on fibroblasts affected the cellular senescence of their surrounding cells, ADSCs. The results showed that senescence factors in ADSCs were suppressed by culture medium from senescent fibroblasts (SF-CM) treated with GLE compared to the SF-CM-only treated group. Furthermore, the regenerative ability of ADSCs was promoted in the GLE-treated SF-CM group. ADSC migration was stimulated by upregulating the levels of α-smooth muscle actin, collagen type I alpha 2, and vascular endothelial growth factor expression through the PI3K/AKT pathway. Those results indicate that GLE can exert regenerative ability by regulating fibroblasts, and adipocyte interactions, improving cellular senescence. We conducted a clinical trial of subjects over 45 years of age to confirm the anti-ageing effects of GLE in vivo and observed changes in ageing parameters, such as skin wrinkles and volume on the face (IRB No. DM-IRB-2023-809-01-T1). The results showed that GLE-containing cream was more effective in improving skin wrinkles, elasticity, density, thickness, and volume around sunken eyes after 4 weeks of use than placebo. In conclusion, GLE plays an important role in inhibiting the ageing transition to ADSCs by inhibiting the senescence of fibroblasts and can be a promising anti-ageing strategy.
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Affiliation(s)
- Jieun Woo
- BioSpectrum Life Science Institute, A1805, U-TOWER, 767, Yongin, Republic of Korea
| | - Hyanggi Ji
- BioSpectrum Life Science Institute, A1805, U-TOWER, 767, Yongin, Republic of Korea
| | - Kyungeun Jeon
- BioSpectrum Life Science Institute, A1805, U-TOWER, 767, Yongin, Republic of Korea
| | - Hongbae Kim
- BioSpectrum Life Science Institute, A1805, U-TOWER, 767, Yongin, Republic of Korea
| | - Sohyun Yoon
- Dermacle Inc., A1606, U-TOWER, 767, Yongin, Republic of Korea
| | - Yunhee Hwang
- Dermacle Inc., A1606, U-TOWER, 767, Yongin, Republic of Korea
| | - Eunae Cho
- BioSpectrum Life Science Institute, A1805, U-TOWER, 767, Yongin, Republic of Korea
| | - Deokhoon Park
- BioSpectrum Life Science Institute, A1805, U-TOWER, 767, Yongin, Republic of Korea
| | - Eunsun Jung
- BioSpectrum Life Science Institute, A1805, U-TOWER, 767, Yongin, Republic of Korea
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4
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Kumar S, Basu M, Ghosh MK. E3 ubiquitin ligases and deubiquitinases in colorectal cancer: Emerging molecular insights and therapeutic opportunities. BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR CELL RESEARCH 2024; 1871:119827. [PMID: 39187067 DOI: 10.1016/j.bbamcr.2024.119827] [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: 04/22/2024] [Revised: 08/21/2024] [Accepted: 08/21/2024] [Indexed: 08/28/2024]
Abstract
Colorectal cancer (CRC) presents ongoing challenges due to limited treatment effectiveness and a discouraging prognosis, underscoring the need for ground-breaking therapeutic approaches. This review delves into the pivotal role of E3 ubiquitin ligases and deubiquitinases (DUBs), underscoring their role as crucial regulators for tumor suppression and oncogenesis in CRC. We spotlight the diverse impact of E3 ligases and DUBs on CRC's biological processes and their remarkable versatility. We closely examine their specific influence on vital signaling pathways, particularly Wnt/β-catenin and NF-κB. Understanding these regulatory mechanisms is crucial for unravelling the complexities of CRC progression. Importantly, we explore the untapped potential of E3 ligases and DUBs as novel CRC treatment targets, discussing aspects that may guide more effective therapeutic strategies. In conclusion, our concise review illuminates the E3 ubiquitin ligases and deubiquitinases pivotal role in CRC, offering insights to inspire innovative approaches for transforming the treatment landscape in CRC.
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Affiliation(s)
- Sunny Kumar
- Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology (CSIR-IICB), TRUE Campus, CN-6, Sector-V, Salt Lake, Kolkata-700091 & Academy of Scientific and Innovative Research, Ghaziabad, Uttar Pradesh 201 002, India
| | - Malini Basu
- Department of Microbiology, Dhruba Chand Halder College, Dakshin Barasat, South 24 Paraganas, PIN - 743372, India
| | - Mrinal K Ghosh
- Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology (CSIR-IICB), TRUE Campus, CN-6, Sector-V, Salt Lake, Kolkata-700091 & Academy of Scientific and Innovative Research, Ghaziabad, Uttar Pradesh 201 002, India.
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dos Santos GA, Magdaleno GDV, de Magalhães JP. Evidence of a pan-tissue decline in stemness during human aging. Aging (Albany NY) 2024; 16:5796-5810. [PMID: 38604248 PMCID: PMC11042951 DOI: 10.18632/aging.205717] [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: 10/08/2023] [Accepted: 02/02/2024] [Indexed: 04/13/2024]
Abstract
Despite their biological importance, the role of stem cells in human aging remains to be elucidated. In this work, we applied a machine learning methodology to GTEx transcriptome data and assigned stemness scores to 17,382 healthy samples from 30 human tissues aged between 20 and 79 years. We found that ~60% of the studied tissues exhibit a significant negative correlation between the subject's age and stemness score. The only significant exception was the uterus, where we observed an increased stemness with age. Moreover, we observed that stemness is positively correlated with cell proliferation and negatively correlated with cellular senescence. Finally, we also observed a trend that hematopoietic stem cells derived from older individuals might have higher stemness scores. In conclusion, we assigned stemness scores to human samples and show evidence of a pan-tissue loss of stemness during human aging, which adds weight to the idea that stem cell deterioration may contribute to human aging.
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Affiliation(s)
- Gabriel Arantes dos Santos
- Laboratory of Medical Investigation (LIM55), Urology Department, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo 01246 903, Brazil
- Genomics of Ageing and Rejuvenation Lab, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2WB, United Kingdom
| | | | - João Pedro de Magalhães
- Genomics of Ageing and Rejuvenation Lab, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2WB, United Kingdom
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Guilhot C, Catenacci M, Lofaro S, Rudnicki MA. The satellite cell in skeletal muscle: A story of heterogeneity. Curr Top Dev Biol 2024; 158:15-51. [PMID: 38670703 DOI: 10.1016/bs.ctdb.2024.01.018] [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] [Indexed: 04/28/2024]
Abstract
Skeletal muscle is a highly represented tissue in mammals and is composed of fibers that are extremely adaptable and capable of regeneration. This characteristic of muscle fibers is made possible by a cell type called satellite cells. Adjacent to the fibers, satellite cells are found in a quiescent state and located between the muscle fibers membrane and the basal lamina. These cells are required for the growth and regeneration of skeletal muscle through myogenesis. This process is known to be tightly sequenced from the activation to the differentiation/fusion of myofibers. However, for the past fifteen years, researchers have been interested in examining satellite cell heterogeneity and have identified different subpopulations displaying distinct characteristics based on localization, quiescence state, stemness capacity, cell-cycle progression or gene expression. A small subset of satellite cells appears to represent multipotent long-term self-renewing muscle stem cells (MuSC). All these distinctions led us to the hypothesis that the characteristics of myogenesis might not be linear and therefore may be more permissive based on the evidence that satellite cells are a heterogeneous population. In this review, we discuss the different subpopulations that exist within the satellite cell pool to highlight the heterogeneity and to gain further understanding of the myogenesis progress. Finally, we discuss the long term self-renewing MuSC subpopulation that is capable of dividing asymmetrically and discuss the molecular mechanisms regulating MuSC polarization during health and disease.
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Affiliation(s)
- Corentin Guilhot
- The Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Marie Catenacci
- The Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Stephanie Lofaro
- The Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Michael A Rudnicki
- The Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
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Al-Balushi E, Al Marzouqi A, Tavoosi S, Baghsheikhi AH, Sadri A, Aliabadi LS, Salarabedi MM, Rahman SA, Al-Yateem N, Jarrahi AM, Halimi A, Ahmadvand M, Abdel-Rahman WM. Comprehensive analysis of the role of ubiquitin-specific peptidases in colorectal cancer: A systematic review. World J Gastrointest Oncol 2024; 16:197-213. [PMID: 38292842 PMCID: PMC10824112 DOI: 10.4251/wjgo.v16.i1.197] [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: 09/24/2023] [Revised: 11/05/2023] [Accepted: 12/07/2023] [Indexed: 01/11/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is the third most frequent and the second most fatal cancer. The search for more effective drugs to treat this disease is ongoing. A better understanding of the mechanisms of CRC development and progression may reveal new therapeutic strategies. Ubiquitin-specific peptidases (USPs), the largest group of the deubiquitinase protein family, have long been implicated in various cancers. There have been numerous studies on the role of USPs in CRC; however, a comprehensive view of this role is lacking. AIM To provide a systematic review of the studies investigating the roles and functions of USPs in CRC. METHODS We systematically queried the MEDLINE (via PubMed), Scopus, and Web of Science databases. RESULTS Our study highlights the pivotal role of various USPs in several processes implicated in CRC: Regulation of the cell cycle, apoptosis, cancer stemness, epithelial-mesenchymal transition, metastasis, DNA repair, and drug resistance. The findings of this study suggest that USPs have great potential as drug targets and noninvasive biomarkers in CRC. The dysregulation of USPs in CRC contributes to drug resistance through multiple mechanisms. CONCLUSION Targeting specific USPs involved in drug resistance pathways could provide a novel therapeutic strategy for overcoming resistance to current treatment regimens in CRC.
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Affiliation(s)
- Eman Al-Balushi
- College of Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Amina Al Marzouqi
- College of Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Shima Tavoosi
- Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan 81746-73441, Iran
| | - Amir Hossein Baghsheikhi
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran 11365/4435, Iran
| | - Arash Sadri
- Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran 1416634793, Iran
| | - Leyla Sharifi Aliabadi
- Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology, and Cell Therapy, Tehran University of Medical Sciences, Tehran 1416634793, Iran
| | - Mohammad-Mahdi Salarabedi
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1983969411, Iran
| | - Syed Azizur Rahman
- College of Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Nabeel Al-Yateem
- Department of Nursing, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Alireza Mosavi Jarrahi
- Cancer Research Centre, Shahid Beheshti University of Medical Sciences, Tehran 1983969411, Iran
| | - Aram Halimi
- Cancer Research Centre, Shahid Beheshti University of Medical Sciences, Tehran 1983969411, Iran
| | - Mohammad Ahmadvand
- Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology, and Cell Therapy, Tehran University of Medical Sciences , Tehran 1416634793, Iran
| | - Wael M Abdel-Rahman
- Department of Medical Laboratory Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
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Jain DP, Dinakar YH, Kumar H, Jain R, Jain V. The multifaceted role of extracellular vesicles in prostate cancer-a review. CANCER DRUG RESISTANCE (ALHAMBRA, CALIF.) 2023; 6:481-498. [PMID: 37842237 PMCID: PMC10571058 DOI: 10.20517/cdr.2023.17] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 06/08/2023] [Accepted: 07/20/2023] [Indexed: 10/17/2023]
Abstract
Prostate cancer is the second most prominent form of cancer in men and confers the highest mortality after lung cancer. The term "extracellular vesicles" refers to minute endosomal-derived membrane microvesicles and it was demonstrated that extracellular vesicles affect the environment in which tumors originate. Extracellular vesicles' involvement is also established in the development of drug resistance, angiogenesis, stemness, and radioresistance in various cancers including prostate cancer. Extracellular vesicles influence the general environment, processes, and growth of prostate cancer and can be a potential area that offers a significant lead in prostate cancer therapy. In this review, we have elaborated on the multifaceted role of extracellular vesicles in various processes involved in the development of prostate cancer, and their multitude of applications in the diagnosis and treatment of prostate cancer through the encapsulation of various bioactives.
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Affiliation(s)
- Divya Prakash Jain
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570015, India
| | - Yirivinti Hayagreeva Dinakar
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570015, India
| | - Hitesh Kumar
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570015, India
| | - Rupshee Jain
- Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570015, India
| | - Vikas Jain
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570015, India
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Kałuzińska-Kołat Ż, Kołat D, Kośla K, Płuciennik E, Bednarek AK. Delineating the glioblastoma stemness by genes involved in cytoskeletal rearrangements and metabolic alterations. World J Stem Cells 2023; 15:302-322. [PMID: 37342224 PMCID: PMC10277965 DOI: 10.4252/wjsc.v15.i5.302] [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: 12/10/2022] [Revised: 02/03/2023] [Accepted: 03/08/2023] [Indexed: 05/26/2023] Open
Abstract
Literature data on glioblastoma ongoingly underline the link between metabolism and cancer stemness, the latter is one responsible for potentiating the resistance to treatment, inter alia due to increased invasiveness. In recent years, glioblastoma stemness research has bashfully introduced a key aspect of cytoskeletal rearrangements, whereas the impact of the cytoskeleton on invasiveness is well known. Although non-stem glioblastoma cells are less invasive than glioblastoma stem cells (GSCs), these cells also acquire stemness with greater ease if characterized as invasive cells and not tumor core cells. This suggests that glioblastoma stemness should be further investigated for any phenomena related to the cytoskeleton and metabolism, as they may provide new invasion-related insights. Previously, we proved that interplay between metabolism and cytoskeleton existed in glioblastoma. Despite searching for cytoskeleton-related processes in which the investigated genes might have been involved, not only did we stumble across the relation to metabolism but also reported genes that were found to be implicated in stemness. Thus, dedicated research on these genes in GSCs seems justifiable and might reveal novel directions and/or biomarkers that could be utilized in the future. Herein, we review the previously identified cytoskeleton/metabolism-related genes through the prism of glioblastoma stemness.
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Affiliation(s)
- Żaneta Kałuzińska-Kołat
- Department of Experimental Surgery, Medical University of Lodz, Lodz 90-136, Lodzkie, Poland
- Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz 90-752, Lodzkie, Poland.
| | - Damian Kołat
- Department of Experimental Surgery, Medical University of Lodz, Lodz 90-136, Lodzkie, Poland
- Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz 90-752, Lodzkie, Poland
| | - Katarzyna Kośla
- Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz 90-752, Lodzkie, Poland
| | - Elżbieta Płuciennik
- Department of Functional Genomics, Medical University of Lodz, Lodz 90-752, Lodzkie, Poland
| | - Andrzej K Bednarek
- Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz 90-752, Lodzkie, Poland
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Nallasamy P, Nimmakayala RK, Parte S, Are AC, Batra SK, Ponnusamy MP. Tumor microenvironment enriches the stemness features: the architectural event of therapy resistance and metastasis. Mol Cancer 2022; 21:225. [PMID: 36550571 PMCID: PMC9773588 DOI: 10.1186/s12943-022-01682-x] [Citation(s) in RCA: 112] [Impact Index Per Article: 37.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 11/16/2022] [Indexed: 12/24/2022] Open
Abstract
Cancer divergence has many facets other than being considered a genetic term. It is a tremendous challenge to understand the metastasis and therapy response in cancer biology; however, it postulates the opportunity to explore the possible mechanism in the surrounding tumor environment. Most deadly solid malignancies are distinctly characterized by their tumor microenvironment (TME). TME consists of stromal components such as immune, inflammatory, endothelial, adipocytes, and fibroblast cells. Cancer stem cells (CSCs) or cancer stem-like cells are a small sub-set of the population within cancer cells believed to be a responsible player in the self-renewal, metastasis, and therapy response of cancer cells. The correlation between TME and CSCs remains an enigma in understanding the events of metastasis and therapy resistance in cancer biology. Recent evidence suggests that TME dictates the CSCs maintenance to arbitrate cancer progression and metastasis. The immune, inflammatory, endothelial, adipocyte, and fibroblast cells in the TME release growth factors, cytokines, chemokines, microRNAs, and exosomes that provide cues for the gain and maintenance of CSC features. These intricate cross-talks are fueled to evolve into aggressive, invasive, migratory phenotypes for cancer development. In this review, we have abridged the recent developments in the role of the TME factors in CSC maintenance and how these events influence the transition of tumor progression to further translate into metastasis and therapy resistance in cancer.
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Affiliation(s)
- Palanisamy Nallasamy
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA
| | - Rama Krishna Nimmakayala
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA
| | - Seema Parte
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA
| | - Abhirup C Are
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA
| | - Surinder K Batra
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
- Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
- Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
| | - Moorthy P Ponnusamy
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
- Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
- Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
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11
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Pooled evidence from preclinical and clinical studies for stem cell-based therapy in ARDS and COVID-19. Mol Cell Biochem 2022; 478:1487-1518. [PMID: 36394787 DOI: 10.1007/s11010-022-04601-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 10/24/2022] [Indexed: 11/18/2022]
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12
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MITOCHONDRIA: Mitochondrial dynamics in the regulation of stem cells. Int J Biochem Cell Biol 2022; 144:106158. [DOI: 10.1016/j.biocel.2022.106158] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 01/11/2022] [Accepted: 01/14/2022] [Indexed: 12/24/2022]
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13
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Devi V. K. A, Shyam R, Palaniappan A, Jaiswal AK, Oh TH, Nathanael AJ. Self-Healing Hydrogels: Preparation, Mechanism and Advancement in Biomedical Applications. Polymers (Basel) 2021; 13:3782. [PMID: 34771338 PMCID: PMC8587783 DOI: 10.3390/polym13213782] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 10/25/2021] [Accepted: 10/26/2021] [Indexed: 12/13/2022] Open
Abstract
Polymeric hydrogels are widely explored materials for biomedical applications. However, they have inherent limitations like poor resistance to stimuli and low mechanical strength. This drawback of hydrogels gave rise to ''smart self-healing hydrogels'' which autonomously repair themselves when ruptured or traumatized. It is superior in terms of durability and stability due to its capacity to reform its shape, injectability, and stretchability thereby regaining back the original mechanical property. This review focuses on various self-healing mechanisms (covalent and non-covalent interactions) of these hydrogels, methods used to evaluate their self-healing properties, and their applications in wound healing, drug delivery, cell encapsulation, and tissue engineering systems. Furthermore, composite materials are used to enhance the hydrogel's mechanical properties. Hence, findings of research with various composite materials are briefly discussed in order to emphasize the healing capacity of such hydrogels. Additionally, various methods to evaluate the self-healing properties of hydrogels and their recent advancements towards 3D bioprinting are also reviewed. The review is concluded by proposing several pertinent challenges encountered at present as well as some prominent future perspectives.
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Affiliation(s)
- Anupama Devi V. K.
- Tissue Engineering Group, Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India; (A.D.V.K.); (R.S.); (A.P.)
- School of Bio Sciences and Technology (SBST), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Rohin Shyam
- Tissue Engineering Group, Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India; (A.D.V.K.); (R.S.); (A.P.)
- School of Bio Sciences and Technology (SBST), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Arunkumar Palaniappan
- Tissue Engineering Group, Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India; (A.D.V.K.); (R.S.); (A.P.)
| | - Amit Kumar Jaiswal
- Tissue Engineering Group, Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India; (A.D.V.K.); (R.S.); (A.P.)
| | - Tae-Hwan Oh
- School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Korea;
| | - Arputharaj Joseph Nathanael
- Tissue Engineering Group, Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India; (A.D.V.K.); (R.S.); (A.P.)
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14
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Purwaningrum M, Jamilah NS, Purbantoro SD, Sawangmake C, Nantavisai S. Comparative characteristic study from bone marrow-derived mesenchymal stem cells. J Vet Sci 2021; 22:e74. [PMID: 34697921 PMCID: PMC8636658 DOI: 10.4142/jvs.2021.22.e74] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 08/03/2021] [Accepted: 08/05/2021] [Indexed: 11/29/2022] Open
Abstract
Tissue engineering has been extensively investigated and proffered to be a potential platform for novel tissue regeneration. The utilization of mesenchymal stem cells (MSCs) from various sources has been widely explored and compared. In this regard, MSCs derived from bone marrow have been proposed and described as a promising cell resource due to their high yield of isolated cells with colony-forming potential, self-renewal capacity, MSC surface marker expression, and multi-lineage differentiation capacities in vitro. However, there is evidence for bone marrow MSCs (BM-MSCs) both in vitro and in vivo from different species presenting identical and distinct potential stemness characteristics. In this review, the fundamental knowledge of the growth kinetics and stemness properties of BM-MSCs in different animal species and humans are compared and summarized. Finally, to provide a full perspective, this review will procure results of current information studies focusing on the use of BM-MSCs in clinical practice.
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Affiliation(s)
- Medania Purwaningrum
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Veterinary Pharmacology and Stem Cell Research Laboratory, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand.,Department of Biochemistry, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
| | - Nabila Syarifah Jamilah
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Veterinary Pharmacology and Stem Cell Research Laboratory, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand
| | - Steven Dwi Purbantoro
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Veterinary Pharmacology and Stem Cell Research Laboratory, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand
| | - Chenphop Sawangmake
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Veterinary Pharmacology and Stem Cell Research Laboratory, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand.,Veterinary Stem Cell and Bioengineering Research Unit, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand.,Department of Pharmacology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand
| | - Sirirat Nantavisai
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Veterinary Pharmacology and Stem Cell Research Laboratory, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand.,Veterinary Stem Cell and Bioengineering Research Unit, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand.
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15
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Chung WM, Molony RD, Lee YF. Non-stem bladder cancer cell-derived extracellular vesicles promote cancer stem cell survival in response to chemotherapy. Stem Cell Res Ther 2021; 12:533. [PMID: 34627375 PMCID: PMC8502272 DOI: 10.1186/s13287-021-02600-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 09/23/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Chemosenstive non-stem cancer cells (NSCCs) constitute the bulk of tumors and are considered as part of the cancer stem cell (CSC) niche in the tumor microenvironment (TME). Tumor-derived extracellular vesicles (EVs) mediate the communication between tumors and the TME. In this study, we sought to investigate the impacts of EVs released by NSCCs on the maintenance of CSC properties and chemoresistance. METHODS We employed murine MB49 bladder cancer (BC) sub-lines representing CSCs and NSCCs as a model system. Chemotherapy drugs were used to treat NSCCs in order to collect conditioned EVs. The impacts of NSCC-derived EVs on CSC progression were evaluated through sphere formation, cytotoxicity, migration, and invasion assays, and by analyzing surface marker expression on these BC cells. Differential proteomic analyses were conducted to identify cargo protein candidates involved in the EV-mediated communication between NSCCs and CSCs. RESULTS NSCC-derived EVs contained cargo proteins enriched in proteostasis-related functions, and significantly altered the development of CSCs such that they were more intrinsically chemoresistant, aggressive, and better able to undergo self-renewal. CONCLUSIONS We thus identified a novel communication mechanism whereby NSCC-EVs can alter the relative fitness of CSCs to promote disease progression and the acquisition of chemoresistance.
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Affiliation(s)
- Wei-Min Chung
- Department of Urology, University of Rochester Medical Center, 601 Elmwood Ave, Box 656, Rochester, NY, 14642, USA
| | - Ryan D Molony
- Department of Urology, University of Rochester Medical Center, 601 Elmwood Ave, Box 656, Rochester, NY, 14642, USA
| | - Yi-Fen Lee
- Department of Urology, University of Rochester Medical Center, 601 Elmwood Ave, Box 656, Rochester, NY, 14642, USA.
- Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA.
- Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.
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16
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Kryvoshlyk I. CIRCULATING TUMOR CELLS: WHERE WE LEFT OFF? BIOTECHNOLOGIA ACTA 2021. [DOI: 10.15407/biotech14.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Cancer metastasis and recurrence are the leading causes of cancer-related death. Tumor cells which leave the primary or secondary tumors and shed into the bloodstream are called circulating tumor cells (CTC). These cells are the key drivers of cancer dissemination to surrounding tissues and to distant organs. The use of CTC in clinical practice necessitates the deep insight into their biology, as well as into their role in cancer evasion of immune surveillance, tumor resistance to chemo- radio- and immunotherapies and metastatic dormancy. Aim. The purpose of the work was to review the current knowledge on the CTC biology, as well as the prospects for their use for the diagnosis and targeted treatment of metastatic disease. Methods. The work proposed the integrative literature review using MEDLINE, Biological Abstracts and EMBASE databases. Results. This review summarizes and discusses historical milestones and current data concerning СTС biology, the main stages of their life cycle, their role in metastatic cascade, clinical prospects for their use as markers for the diagnosis and prognostication of the disease course, as well as targets for cancer treatment. Conclusions. Significant progress in the area of CTC biology and their use in cancer theranostics convincingly proved the attractiveness of these cells as targets for cancer prognosis and therapy. The effective use of liquid biopsy with quantitative and phenotypic characteristics of CTCs is impeded by the imperfection of the methodology for taking biological material and by the lack of reliable markers for assessing the metastatic potential of CTCs of various origins. The variety of mechanisms of tumor cells migration and invasion requires the development of complex therapeutic approaches for anti-metastatic therapy targeting CTCs. Efforts to address these key issues could help developing new and effective cancer treatment strategies.
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17
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Ter Huurne M, Stunnenberg HG. G1-phase progression in pluripotent stem cells. Cell Mol Life Sci 2021; 78:4507-4519. [PMID: 33884444 PMCID: PMC8195903 DOI: 10.1007/s00018-021-03797-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 01/19/2021] [Accepted: 02/19/2021] [Indexed: 11/10/2022]
Abstract
During early embryonic development both the rapid increase in cell number and the expression of genes that control developmental decisions are tightly regulated. Accumulating evidence has indicated that these two seemingly independent processes are mechanistically intertwined. The picture that emerges from studies on the cell cycle of embryonic stem cells is one in which proteins that promote cell cycle progression prevent differentiation and vice versa. Here, we review which transcription factors and signalling pathways play a role in both maintenance of pluripotency as well as cell cycle progression. We will not only describe the mechanism behind their function but also discuss the role of these regulators in different states of mouse pluripotency. Finally, we elaborate on how canonical cell cycle regulators impact on the molecular networks that control the maintenance of pluripotency and lineage specification.
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Affiliation(s)
- Menno Ter Huurne
- Department of Molecular Biology, Faculty of Science, Radboud University, 6525GA, Nijmegen, The Netherlands
- Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Rd, Parkville, Melbourne, VIC, 3052, Australia
| | - Hendrik G Stunnenberg
- Department of Molecular Biology, Faculty of Science, Radboud University, 6525GA, Nijmegen, The Netherlands.
- Princess Maxima Centre for Pediatric Oncology, Heidelberglaan 25, 3584 CS, Utrecht, The Netherlands.
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18
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Hayat H, Hayat H, Dwan BF, Gudi M, Bishop JO, Wang P. A Concise Review: The Role of Stem Cells in Cancer Progression and Therapy. Onco Targets Ther 2021; 14:2761-2772. [PMID: 33907419 PMCID: PMC8068480 DOI: 10.2147/ott.s260391] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Accepted: 03/23/2021] [Indexed: 12/11/2022] Open
Abstract
The properties of cancer stem cells (CSCs) have recently gained attention as an avenue of intervention for cancer therapy. In this review, we highlight some of the key roles of CSCs in altering the cellular microenvironment in favor of cancer progression. We also report on various studies in this field which focus on transformative properties of CSCs and their influence on surrounding cells or targets through the release of cellular cargo in the form of extracellular vesicles. The findings from these studies encourage the development of novel interventional therapies that can target and prevent cancer through efficient, more effective methods. These methods include targeting immunosuppressive proteins and biomarkers, promoting immunization against tumors, exosome-mediated CSC conversion, and a focus on the quiescent properties of CSCs and their role in cancer progression. The resulting therapeutic benefit and transformative potential of these novel approaches to stem cell-based cancer therapy provide a new direction in cancer treatment, which can focus on nanoscale, molecular properties of the cellular microenvironment and establish a more precision medicine-oriented paradigm of treatment.
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Affiliation(s)
- Hasaan Hayat
- Precision Health Program, Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI, USA
- Lyman Briggs College, Michigan State University, East Lansing, MI, USA
| | - Hanaan Hayat
- Precision Health Program, Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI, USA
- Lyman Briggs College, Michigan State University, East Lansing, MI, USA
- Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA
| | - Bennett Francis Dwan
- Precision Health Program, Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI, USA
- College of Natural Science, Michigan State University, East Lansing, MI, USA
| | - Mithil Gudi
- Precision Health Program, Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI, USA
- College of Natural Science, Michigan State University, East Lansing, MI, USA
| | - Jack Owen Bishop
- Precision Health Program, Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI, USA
- College of Natural Science, Michigan State University, East Lansing, MI, USA
| | - Ping Wang
- Precision Health Program, Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI, USA
- Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI, USA
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