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Lavreysen O, Bakusic J, Abatzi TA, Geerts A, Mateusen M, Bashkin O, Koscec Bjelajac A, Dopelt K, du Prel JB, Franic Z, Guseva Canu I, Kiran S, Merisalu E, Pereira CC, Roquelaure Y, Godderis L. An overview of work-related stress assessment. J Affect Disord 2025; 383:240-259. [PMID: 40280433 DOI: 10.1016/j.jad.2025.04.076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Revised: 04/06/2025] [Accepted: 04/18/2025] [Indexed: 04/29/2025]
Abstract
OBJECTIVE Work-related stress (WRS) is associated with the development of various health issues and long-term absence from the workplace. Adequate measurement of WRS is essential to assess its prevalence, risks, and effectiveness of preventive interventions. The aim of this review was to provide an overview of different categories of WRS assessment: 1) self-assessment, 2) external assessment, and 3) biomarkers. METHODS The databases MEDLINE, PsycINFO, EMBASE, CINAHL, and Web of Science have been searched until July 2024 for studies comprising self-assessment or external assessment of WRS, and WRS biomarkers. The self-assessment studies were further evaluated following the COSMIN guidelines. RESULTS In this review, a total of 15,749 articles were screened. The final analysis included 53 studies on self-assessment of WRS, 33 articles on external assessment of WRS and 167 articles on stress biomarkers. Within self-assessment studies, four instruments were included in the analysis: Job Content Questionnaire, Effort Reward Imbalance Questionnaire, Copenhagen Psychosocial Questionnaire II and the Demand-Control-Support Questionnaire. The studies applying external assessment used job-exposure matrices, work register data, ethnography, digital tools, and external observation. The identified WRS biomarkers were associated with the sympathetic adrenal medullary axis, the hypothalamic pituitary adrenal axis, immune response and inflammation, and haemostatic, metabolic and (epi)genetic biomarkers. CONCLUSION The available evidence does not support the claim that there is a singular golden standard for assessing WRS. Inclusion of objective parameters and the interaction with subjective parameters and biological markers has to be studied to receive a broader view of WRS.
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Affiliation(s)
- Olivia Lavreysen
- Department of Public Health and Primary Care, Centre for Environment and Health, KU Leuven, Leuven, Belgium.
| | - Jelena Bakusic
- Department of Public Health and Primary Care, Centre for Environment and Health, KU Leuven, Leuven, Belgium; University Psychiatric Centre KU Leuven (UPC KU Leuven), KU Leuven, Kortenberg, Belgium
| | - Thalia-Anthi Abatzi
- Department of Public Health and Primary Care, Centre for Environment and Health, KU Leuven, Leuven, Belgium; Retirement service of civil servants' social insurance, BVaeb, Vienna, Austria
| | - Annelien Geerts
- Department of Public Health and Primary Care, Centre for Environment and Health, KU Leuven, Leuven, Belgium
| | - Mies Mateusen
- Department of Public Health and Primary Care, Centre for Environment and Health, KU Leuven, Leuven, Belgium
| | - Osnat Bashkin
- Department of Public Health, Ashkelon Academic College, Ashkelon, Israel
| | | | - Keren Dopelt
- Department of Public Health, Ashkelon Academic College, Ashkelon, Israel
| | - Jean-Baptist du Prel
- Department of Occupational Health Science, University of Wuppertal, Wuppertal, Germany
| | - Zrinka Franic
- Institute for Medical Research and Occupational Health, Zagreb, Croatia
| | - Irina Guseva Canu
- Department of Occupational and Environmental Health, Unisanté, University of Lausanne, Lausanne, Switzerland
| | - Sibel Kiran
- Department of Public Health, Koç University, Istanbul, Turkey
| | - Eda Merisalu
- Estonian University of Life Sciences, Tartu, Estonia
| | - Cristiana Costa Pereira
- Environmental Health Department, National Institute of Health, Portugal; EPIUnit, Institute of Public Health, University of Porto, Portugal; Laboratory for Integrative and Translational Research in Population Health (ITR), Portugal; Environmental Hygiene and Human biological monitoring Unit, Department of Health Protection, Laboratoire national de santé, Luxembourg
| | - Yves Roquelaure
- Univ Angers, CHU Angers, Irset (Institut de recherche en santé, environnement et travail), Angers, France
| | - Lode Godderis
- Department of Public Health and Primary Care, Centre for Environment and Health, KU Leuven, Leuven, Belgium; IDEWE, External Service for Prevention and Protection at Work, Heverlee, Belgium
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Asimakopoulos T, Tsaroucha A, Kouri M, Pasqualucci A, Varrassi G, Leoni MLG, Rekatsina M. The Role of Biomarkers in Acute Pain: A Narrative Review. Pain Ther 2025; 14:775-789. [PMID: 40088258 PMCID: PMC12085431 DOI: 10.1007/s40122-025-00718-6] [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: 01/09/2025] [Accepted: 02/25/2025] [Indexed: 03/17/2025] Open
Abstract
Acute pain, a critical aspect of patient care, presents a challenge due to its subjective nature and complex biological underpinnings. Biomarkers for acute pain promise a paradigm shift in how pain is perceived, diagnosed, and managed. The study of genetic, inflammatory, and neurotransmission markers associated with pain experience may hold the key for the development of personalized and effective pain management strategies. This narrative review explores the neurobiological pathways of acute pain, encompassing inflammatory responses and neurotransmission mechanisms. It synthesizes current research on the identification and clinical application of biomarkers, emphasizing their potential to enhance diagnostic precision, treatment effectiveness, and risk prediction. We underscore the promising role of acute pain biomarkers in identifying patients at risk for developing acute and potentially chronic pain, predicting patients' response to pharmacological interventions, and aiding in the development of novel therapeutic and pain preventive strategies. The evolving landscape of biomarker research not only deepens our understanding of pain mechanisms but also lays the foundation for more tailored and patient-specific healthcare interventions.
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Affiliation(s)
- Thalis Asimakopoulos
- School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
- 1st Department of Anesthesiology and Pain Medicine, Aretaieion University Hospital, National and Kapodistrian University of Athens, Athens, Greece.
| | - Athanasia Tsaroucha
- 1st Department of Anesthesiology and Pain Medicine, Aretaieion University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Kouri
- Department of Oral Medicine & Pathology and Hospital Dentistry, School of Dentistry, National and Kapodistrian University of Athens, 11527, Athens, Greece
| | - Alberto Pasqualucci
- Department of Anesthesia and Pain Medicine, University of Perugia, 06100, Perugia, Italy
| | | | - Matteo Luigi Giuseppe Leoni
- Department of Medical and Surgical Sciences and Translational Medicine, "La Sapienza" University of Rome, Rome, Italy
| | - Martina Rekatsina
- 1st Department of Anesthesiology and Pain Medicine, Aretaieion University Hospital, National and Kapodistrian University of Athens, Athens, Greece.
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Sun X, Xiang T, Xie L, Ren Q, Chang J, Jiang W, Jin Z, Yang X, Ren W, Yu Y. Recent advances in fluorescent nanomaterials designed for biomarker detection and imaging. Mater Today Bio 2025; 32:101763. [PMID: 40331150 PMCID: PMC12053759 DOI: 10.1016/j.mtbio.2025.101763] [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: 01/24/2025] [Revised: 04/09/2025] [Accepted: 04/11/2025] [Indexed: 05/08/2025] Open
Abstract
The highly sensitive detection and imaging of biomarkers are critical for early diagnosis, treatment, and prognosis monitoring. The unique size and structure of fluorescent nanomaterials provide key benefits such as excellent photostability, high fluorescence quantum yield, and tunable excitation and emission wavelengths. These properties have led to the widespread application of nanomaterials in fluorescent biomarkers detection and imaging. In this review, we began by introducing the composition of fluorescent probes and discussing the underlying sensing mechanisms. We then summarized recent advances in the use of fluorescent nanomaterials such as quantum dots (QDs), metal nanoclusters (MNCs), carbon dots (CDs), and metal-organic frameworks (MOFs) for biomarker detection and imaging. Additionally, we highlighted the applications of fluorescent nanomaterials in the detection and imaging of small molecules, biomacromolecules, and various biomarkers, including metal ions, bacteria, and circulating tumor cells (CTCs). The challenges and future prospects of fluorescent nanomaterials in biomarker detection and imaging were also discussed. We anticipate that fluorescent nanomaterials will have profound implications for clinical biomarker detection and imaging, with considerable application in both academic research and industrial applications.
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Affiliation(s)
- Xuming Sun
- School of Medical Engineering, Xinxiang Medical University, Xinxiang, 453003, PR China
- Xinxiang Key Laboratory of Neurobiosensor, Xinxiang Medical University, Xinxiang, 453003, PR China
| | - Tong Xiang
- School of Medical Engineering, Xinxiang Medical University, Xinxiang, 453003, PR China
- Xinxiang Key Laboratory of Neurobiosensor, Xinxiang Medical University, Xinxiang, 453003, PR China
| | - Linyan Xie
- School of Mathematical Medicine, Xinxiang Medical University, Xinxiang, 453003, PR China
| | - Qiongqiong Ren
- School of Medical Engineering, Xinxiang Medical University, Xinxiang, 453003, PR China
- Xinxiang Key Laboratory of Neurobiosensor, Xinxiang Medical University, Xinxiang, 453003, PR China
| | - Jinlong Chang
- School of Medical Engineering, Xinxiang Medical University, Xinxiang, 453003, PR China
| | - Wenshuai Jiang
- School of Medical Engineering, Xinxiang Medical University, Xinxiang, 453003, PR China
- Xinxiang Key Laboratory of Neurobiosensor, Xinxiang Medical University, Xinxiang, 453003, PR China
| | - Zhen Jin
- School of Medical Engineering, Xinxiang Medical University, Xinxiang, 453003, PR China
- Xinxiang Key Laboratory of Neurobiosensor, Xinxiang Medical University, Xinxiang, 453003, PR China
| | - Xiuli Yang
- Department of Cardiology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453003, PR China
| | - Wu Ren
- School of Medical Engineering, Xinxiang Medical University, Xinxiang, 453003, PR China
| | - Yi Yu
- School of Medical Engineering, Xinxiang Medical University, Xinxiang, 453003, PR China
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Jallod IMS, Abbas AK, Yaqoob FI, Aziz AAA. Bridging diabetes and cancer: harnessing biomarkers as dual sentinels for diagnosis, prognosis, and therapeutic advancements. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-04209-5. [PMID: 40387929 DOI: 10.1007/s00210-025-04209-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/25/2025] [Accepted: 04/21/2025] [Indexed: 05/20/2025]
Abstract
The complex two-way relationship between diabetes mellitus (DM) and cancer poses a significant global health challenge. Shared mechanisms such as hyperinsulinemia, chronic inflammation, and oxidative stress create an environment that fosters cancer development, increasing the risk for certain cancers in individuals with diabetes, including pancreatic, colorectal, breast, liver, and endometrial malignancies. In this context, biomarkers emerge as essential tools, offering a means to untangle the connections between these two conditions by providing insights into early detection, diagnosis, prognosis, and treatment monitoring. For diabetic patients, biomarkers are particularly valuable as they help differentiate between changes caused by cancer and those driven by metabolic imbalances, illuminating disease evolution. This review examines the unique challenges encountered by diabetic patients with cancer, emphasizing the contributions of targeted biomarkers in identifying cancer subtypes, predicting outcomes, and guiding treatment decisions. We explore organ-specific biomarker profiles across various cancers, including pancreatic, colorectal, breast, liver, and lung, highlighting their potential to enhance diagnostic precision and enable personalized treatment strategies. Ultimately, we aim to illustrate how a deeper understanding of biomarker signatures can inform innovative clinical approaches and improve care for patients facing the dual burden of diabetes and cancer.
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Affiliation(s)
| | | | - Faheemah Ismael Yaqoob
- College of Nursing, Department of Basic Science Nursing, University of Telafer, Telafer, Iraq
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Newton-Tanzer E, Can SN, Demmelmair H, Horak J, Holdt L, Koletzko B, Grote V. Apparent Saturation of Branched-Chain Amino Acid Catabolism After High Dietary Milk Protein Intake in Healthy Adults. J Clin Endocrinol Metab 2025; 110:e1793-e1801. [PMID: 39302872 DOI: 10.1210/clinem/dgae599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Indexed: 09/22/2024]
Abstract
CONTEXT Milk protein contains high concentrations of branched-chain amino acids (BCAA) that play a critical role in anabolism and are implicated in the onset of obesity and chronic disease. Characterizing BCAA catabolism in the postprandial phase could elucidate the impact of protein intake on obesity risk established in the "early protein hypothesis." OBJECTIVE To examine the acute effects of protein content of young child formulas as test meals on BCAA catabolism, observing postprandial plasma concentrations of BCAA in relation to their degradation products. METHODS The TOMI Add-On Study is a randomized, double-blind crossover study in which 27 healthy adults consumed 2 isocaloric young child formulas with alternating higher (HP) and lower (LP) protein and fat content as test meals during separate interventions, while 9 blood samples were obtained over 5 hours. BCAA, branched-chain α-keto acids (BCKA), and acylcarnitines were analyzed using a fully targeted HPLC-ESI-MS/MS approach. RESULTS Mean concentrations of BCAA, BCKA, and acylcarnitines were significantly higher after HP than LP over the 5 postprandial hours, except for the BCKA α-ketoisovalerate (KIVA). The latter metabolite showed higher postprandial concentrations after LP. With increasing mean concentrations of BCAA, concentrations of corresponding BCKA, acylcarnitines, and urea increased until a breakpoint was reached, after which concentrations of degradation products decreased (for all metabolites except valine and KIVA and Carn C4:0-iso). CONCLUSION BCAA catabolism is markedly influenced by protein content of the test meal. We present novel evidence for the apparent saturation of the BCAA degradation pathway in the acute postprandial phase up to 5 hours after consumption.
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Affiliation(s)
- Emily Newton-Tanzer
- Division of Metabolic and Nutritional Medicine, Department Paediatrics, Dr. von Hauner Children's Hospital, LMU University Hospital, LMU Munich, and the German Center for Child and Adolescent Health, site Munich, 80337 Munich, Germany
| | - Sultan Nilay Can
- Division of Metabolic and Nutritional Medicine, Department Paediatrics, Dr. von Hauner Children's Hospital, LMU University Hospital, LMU Munich, and the German Center for Child and Adolescent Health, site Munich, 80337 Munich, Germany
| | - Hans Demmelmair
- Division of Metabolic and Nutritional Medicine, Department Paediatrics, Dr. von Hauner Children's Hospital, LMU University Hospital, LMU Munich, and the German Center for Child and Adolescent Health, site Munich, 80337 Munich, Germany
| | - Jeannie Horak
- Division of Metabolic and Nutritional Medicine, Department Paediatrics, Dr. von Hauner Children's Hospital, LMU University Hospital, LMU Munich, and the German Center for Child and Adolescent Health, site Munich, 80337 Munich, Germany
| | - Lesca Holdt
- Institute of Laboratory Medicine, LMU University Hospital, LMU Munich, 80337 Munich, Germany
| | - Berthold Koletzko
- Division of Metabolic and Nutritional Medicine, Department Paediatrics, Dr. von Hauner Children's Hospital, LMU University Hospital, LMU Munich, and the German Center for Child and Adolescent Health, site Munich, 80337 Munich, Germany
| | - Veit Grote
- Division of Metabolic and Nutritional Medicine, Department Paediatrics, Dr. von Hauner Children's Hospital, LMU University Hospital, LMU Munich, and the German Center for Child and Adolescent Health, site Munich, 80337 Munich, Germany
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Huber C, Zinserling J, Benda N, Vetter T, Rueckbeil M. Methodological Insights on Biomarker-Based Patient Selection: A Review of Scientific Advice Procedures at the European Medicines Agency. Clin Pharmacol Ther 2025; 117:1226-1235. [PMID: 39825875 PMCID: PMC11993284 DOI: 10.1002/cpt.3558] [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: 07/12/2024] [Accepted: 12/20/2024] [Indexed: 01/20/2025]
Abstract
Biomarkers play a pivotal role in the selection and enrollment of trial participants. Particularly, predictive biomarkers help tailor medical care to individual patients; however, also prognostic biomarkers require consideration at the design stage. At the time of initiating a clinical trial, there may be uncertainty about whether a biomarker is predictive or prognostic, and the trial design may need to account for this. Relevant discussions between drug developers and regulators on the role of a biomarker in a specific drug development program are expected to take place during Scientific Advice (SA) procedures. SA procedures at the European Medicines Agency from January 1, 2018, to December 31, 2020, were systematically searched for methodological discussions around the use of predictive or prognostic biomarkers. The final analysis included 45 SA procedures for which key characteristics were summarized quantitatively. Selected methodological issues such as the cutoff selection of continuous biomarkers or study design considerations were elaborated in a qualitative summary. Our results identify commonly encountered points for discussion between drug developers and the European Medicines Agency for biomarker-informed patient selection and enrollment. Identified topics addressed during SA procedures include cutoff selection, study design, multiplicity control, and data-driven subgroup selection. The majority of the identified 45 SA procedures concern development programs in oncology. Addressing these issues upfront will allow for an improved dialogue between drug developers and regulators and support the drug development program and ultimately patient-centered access to medicines.
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Affiliation(s)
- Cynthia Huber
- Department of Medical StatisticsUniversity Medical CenterGöttingenGermany
- Present address:
AbbVie Deutschland GmbH & Co. KGLudwigshafenGermany
| | - Joerg Zinserling
- Federal Institute for Drugs and Medical Devices (BfArM)BonnGermany
| | - Norbert Benda
- Department of Medical StatisticsUniversity Medical CenterGöttingenGermany
- Federal Institute for Drugs and Medical Devices (BfArM)BonnGermany
| | - Thorsten Vetter
- Scientific Advice OfficeEuropean Medicines AgencyAmsterdamThe Netherlands
| | - Marcia Rueckbeil
- Data Analytics and Methods Task ForceEuropean Medicines AgencyAmsterdamThe Netherlands
- Department of Medical StatisticsUniversity Hospital AachenAachenGermany
- Present address:
Sanofi‐Aventis Deutschland GmbHFrankfurt am MainGermany
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Chan II. Blunted cortisol as a biomarker of depression based on the attenuation hypothesis: A Mendelian randomization analysis using depression as exposure. J Affect Disord 2025; 376:398-409. [PMID: 39961449 DOI: 10.1016/j.jad.2025.02.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 02/02/2025] [Accepted: 02/12/2025] [Indexed: 02/21/2025]
Abstract
BACKGROUND Both elevated and blunted cortisol responses have been associated with depression. Previous Mendelian randomization (MR) studies have largely ruled out cortisol as a cause of depression. Based on the attenuation hypothesis, this MR study used depression as exposure to assess whether cortisol might be a consequence and therefore a biomarker of depression. METHODS Strong (P < 5 × 10-8) and independent (r2 < 0.001) single nucleotide polymorphisms (SNPs) associated with broadly defined depression (294,322 cases, 741,438 controls) were used as instruments. These were applied to genetic associations with morning, fasting, and random plasma cortisol in the CORtisol NETwork (CORNET) consortium (n = 25,314), METabolic Syndrome in Men (METSIM) study (n = 6667), and Canadian Longitudinal Study on Aging (CLSA) cohort (n = 8299). Multivariable MR, adjusting for childhood maltreatment and major mental disorders, was conducted to address potential horizontal pleiotropy from dichotomous depression. Instruments were also selected by evidence of colocalization with major depressive disorder to address non-specificity. RESULTS Using 133 SNPs as instruments, depression was inversely associated with morning plasma cortisol (β per log-odds of genetic liability to depression = -0.107 [95 % CI, -0.181 to -0.032]) in the CORNET consortium. Replication in the METSIM study (β = -0.203 [95 % CI, -0.367 to -0.040]) and CLSA cohort (β = -0.091 [95 % CI, -0.220 to 0.039]) showed consistent but not always significant associations. Multivariable MR and follow-up analysis incorporating colocalization supported these findings. CONCLUSIONS Consistent with the attenuation hypothesis, blunted cortisol response appeared to be a consequence and potentially a biomarker of depression. Future studies are needed to provide more interpretable effect sizes and validate other biomarker measures.
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Affiliation(s)
- Io Ieong Chan
- Department of Public Health and Medicinal Administration, Faculty of Health Sciences, University of Macau, Macao SAR, China.
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Falvey CA, Todd JL, Neely ML. Evaluating the performance of a resampling approach for internally validating the association between a time-dependent binary indicator and time-to-event outcome. J Biopharm Stat 2025:1-11. [PMID: 40287853 DOI: 10.1080/10543406.2025.2489293] [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: 08/31/2024] [Accepted: 02/25/2025] [Indexed: 04/29/2025]
Abstract
Identifying clinical or biological risk factors for disease plays a critical role in enabling earlier disease diagnosis, prognostic outcomes assessment, and may inform disease prevention or monitoring practices. One framework commonly examined is understanding the association between a risk factor ever occurring in follow-up and the future risk of an outcome. If such an association is found, researchers are often asked to validate the finding. External validation is often infeasible, and validation may only be performed internally. However, the performance of internal validation methods in the setting of a time-dependent binary indicator and a time-to-event outcome has not been well-studied. We emulated a dataset motivated by real-world serial biomarker observations and performed extensive simulation studies to evaluate the performance of a resampling-based method to internally validate the association between a time-dependent binary indicator and a time-to-event outcome. We found the resampling-based method achieved optimal power for validating such an association while maintaining good Type I error control.
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Affiliation(s)
- Caroline A Falvey
- Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, USA
| | - Jamie L Todd
- Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA
- Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University Medical Center, Durham, NC, USA
| | - Megan L Neely
- Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, USA
- Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA
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Krishnan A. Leucine-rich alpha-2 glycoprotein for detecting small bowel lesions in Crohn's disease: A critical review and the path forward. World J Gastrointest Endosc 2025; 17:106671. [PMID: 40291129 PMCID: PMC12019126 DOI: 10.4253/wjge.v17.i4.106671] [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: 03/04/2025] [Revised: 03/20/2025] [Accepted: 04/02/2025] [Indexed: 04/14/2025] Open
Abstract
The study by Ohno et al provides valuable insights into the role of leucine-rich alpha-2-glycoprotein (LRG) as a potential biomarker for identifying small bowel lesions in Crohn's disease (CD). However, several methodological challenges hinder its immediate use in clinical practice. Notably, the current research was retrospective, lacks comparative studies with fecal calprotectin, and did not provide long-term predictive data. Further prospective studies are needed to improve the applicability of LRG. Moreover, integrating LRG with additional biomarkers and employing artificial intelligence techniques may improve its effectiveness in disease monitoring. Future research should address interobserver variability, assess LRG's cost-effectiveness, and standardize endoscopic healing definitions to ensure broader applicability. Advancing these areas is vital for establishing LRG's role in precision medicine strategies for the management of CD.
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Affiliation(s)
- Arunkumar Krishnan
- Department of Supportive Oncology, Atrium Health Levine Cancer, Charlotte, NC 28204, United States
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Hauptmann M, Nguyen VH, Sollfrank L, Linn SC, Jóźwiak K. Case-only analysis in small studies of predictive biomarkers. Sci Rep 2025; 15:13068. [PMID: 40240472 PMCID: PMC12003872 DOI: 10.1038/s41598-025-96904-9] [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: 10/08/2024] [Accepted: 04/01/2025] [Indexed: 04/18/2025] Open
Abstract
Characteristics of tumors and patients can be used as predictive biomarkers to guide treatment choice. Although many potential biomarkers are evaluated each year, only few will eventually be used since evidence is usually based on small studies leading to inconclusive results. Such data are often analyzed with Cox proportional hazards regression using a multiplicative interaction term between biomarker and treatment, with insufficient power and possibly biased results. Instead of analyzing patients who do (cases) and do not experience (non-cases) the survival event of interest, case-only analysis with logistic regression has been proposed, however with unknown small sample properties. We evaluated the performance of case-only analysis with bias-eliminating Firth correction and confidence intervals obtained with a profile likelihood method in a simulation study tailored to breast cancer. Our results show that this approach is generally inferior to the full cohort analysis but has acceptable properties when the marker is protective or null among patients treated with the standard treatment, the event rate is low (e.g., a rare event and a protective marker) and treatment assignment is independent of the marker level (e.g., in randomized studies). In such situations, the case-only design offers substantial cost savings. However, the model is sensitive to these assumptions.
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Affiliation(s)
- M Hauptmann
- Brandenburg Medical School Theodor Fontane, Institute of Biostatistics and Registry Research, Fehrbelliner Straße 39, 16816, Neuruppin, Germany.
| | - V H Nguyen
- Brandenburg Medical School Theodor Fontane, Institute of Biostatistics and Registry Research, Fehrbelliner Straße 39, 16816, Neuruppin, Germany
- Leibniz Centre for Agricultural Landscape Research (ZALF), Müncheberg, Germany
| | - L Sollfrank
- Brandenburg Medical School Theodor Fontane, Institute of Biostatistics and Registry Research, Fehrbelliner Straße 39, 16816, Neuruppin, Germany
| | - S C Linn
- Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
- Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
- Department of Pathology, University Medical Center, Utrecht, The Netherlands
| | - K Jóźwiak
- Brandenburg Medical School Theodor Fontane, Institute of Biostatistics and Registry Research, Fehrbelliner Straße 39, 16816, Neuruppin, Germany
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Suárez-Jaramillo A, Cifuentes SG, Baldeón M, Cárdenas P. Intestinal Metabolome for Diagnosing and Prognosing Autism Spectrum Disorder in Children: A Systematic Review. Metabolites 2025; 15:213. [PMID: 40278342 PMCID: PMC12029135 DOI: 10.3390/metabo15040213] [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: 02/24/2025] [Revised: 03/10/2025] [Accepted: 03/14/2025] [Indexed: 04/26/2025] Open
Abstract
Background/Objectives: Currently, the diagnosis of autism spectrum disorder (ASD) relies on behavioral observations, frequently causing delays in early identification. Prognostic markers are essential for customizing therapy and monitoring progress. However, there are currently no recognized biomarkers for ASD. The current systematic review aims to analyze studies on the intestinal metabolome in children (both autistic and non-autistic) to identify potential metabolites for diagnostic and prognostic purposes. Methods: We searched Medline, Scopus, Embase, and Web of Science for relevant publications. Results: We identified 11 studies examining the gut metabolome that distinguished between autistic and non-autistic children. These studies also revealed connections between gut metabolites, developmental scores, and symptoms. The substances identified were associated with metabolic pathways such as amino acids, vitamins, lipids, oxidative stress, glycans, xenobiotics, and nucleotides. Conclusions: These findings suggest metabolic changes that may be linked to the causes or development of autism. Although these observations came from a few reports, only high-quality studies were included in this review. Further research is essential to confirm the identified substances as biomarkers.
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Affiliation(s)
- Andrés Suárez-Jaramillo
- Institute of Microbiology, Universidad San Francisco de Quito, Quito 170901, Ecuador; (A.S.-J.); (S.G.C.)
| | - Sara G. Cifuentes
- Institute of Microbiology, Universidad San Francisco de Quito, Quito 170901, Ecuador; (A.S.-J.); (S.G.C.)
| | - Manuel Baldeón
- Facultad de Ciencias Médicas de la Salud y de la Vida, Universidad Internacional del Ecuador, Quito 170411, Ecuador;
- Unidad de Investigación Clínica, Hospital Metropolitano de Quito, Quito 170521, Ecuador
| | - Paúl Cárdenas
- Institute of Microbiology, Universidad San Francisco de Quito, Quito 170901, Ecuador; (A.S.-J.); (S.G.C.)
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Hernandez R, Garcia-Rodriguez NS, Arriaga MA, Perez R, Bala AA, Leandro AC, Diego VP, Almeida M, Parsons JG, Manusov EG, Galan JA. The hepatocellular model of fatty liver disease: from current imaging diagnostics to innovative proteomics technologies. Front Med (Lausanne) 2025; 12:1513598. [PMID: 40109726 PMCID: PMC11919916 DOI: 10.3389/fmed.2025.1513598] [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: 10/18/2024] [Accepted: 02/06/2025] [Indexed: 03/22/2025] Open
Abstract
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a prevalent chronic liver condition characterized by lipid accumulation and inflammation, often progressing to severe liver damage. We aim to review the pathophysiology, diagnostics, and clinical care of MASLD, and review highlights of advances in proteomic technologies. Recent advances in proteomics technologies have improved the identification of novel biomarkers and therapeutic targets, offering insight into the molecular mechanisms underlying MASLD progression. We focus on the application of mass spectrometry-based proteomics including single cell proteomics, proteogenomics, extracellular vesicle (EV-omics), and exposomics for biomarker discovery, emphasizing the potential of blood-based panels for noninvasive diagnosis and personalized medicine. Future research directions are presented to develop targeted therapies and improve clinical outcomes for MASLD patients.
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Affiliation(s)
- Renee Hernandez
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Natasha S Garcia-Rodriguez
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Marco A Arriaga
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Ricardo Perez
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Auwal A Bala
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Ana C Leandro
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
- South Texas Diabetes and Obesity Institute, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Vince P Diego
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
- South Texas Diabetes and Obesity Institute, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Marcio Almeida
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
- South Texas Diabetes and Obesity Institute, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Jason G Parsons
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Eron G Manusov
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Jacob A Galan
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
- South Texas Diabetes and Obesity Institute, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
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13
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Golestan A, Zareinejad M, Ramezani A. Comprehensive biomarker profiles in hematological malignancies: improving diagnosis, prognosis, and treatment. Biomark Med 2025; 19:223-238. [PMID: 40015744 PMCID: PMC11916375 DOI: 10.1080/17520363.2025.2471745] [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] [Received: 10/14/2024] [Accepted: 02/21/2025] [Indexed: 03/01/2025] Open
Abstract
Hematological malignancies present substantial challenges in clinical practice due to their heterogeneity and complex biological profiles. In these diseases, biomarkers - measurable indicators of biological states - are indispensable for diagnosis, prognosis, and therapeutic decision-making. Emerging biomarkers are significantly improving outcomes in hematological cancers by enhancing early detection, refining prognostic assessments, enabling personalized treatment approaches, and optimizing overall patient management. This progress translates into better clinical outcomes and more effective strategies to treat and manage malignancies. The field of biomarker discovery has developed from basic morphological and cytogenetic markers to advanced molecular techniques, including polymerase chain reaction (PCR) and next-generation sequencing (NGS), which have significantly enhanced diagnostic accuracy and led to the development of targeted therapies. Additionally, the recent advent of technologies like mass spectrometry and single-cell RNA sequencing enables comprehensive molecular profiling and reveals novel biomarkers that were previously undetectable. Our aim in this manuscript is to provide a comprehensive overview of recent and novel immunohematological biomarkers, their diagnostic and therapeutic applications, and the future directions of this field.
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Affiliation(s)
- Ali Golestan
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
- Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Science, Shiraz, Iran
| | - Mohammadrasul Zareinejad
- Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Science, Shiraz, Iran
| | - Amin Ramezani
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
- Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Science, Shiraz, Iran
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14
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Emanuelle Pereira Santos V, Luiz de França Neto P, Eda de Oliveira Isídio B, Henrique Bezerra Fontes P, Andrêssa de Moura I, Isabel Santos Cruz B, Máyra Gois de Sousa M, Luana Dos Santos D, de França São Marcos B, Sousa de Pinho S, Mendonça Alves Bandeira B, Loureiro Leão S, de Almeida Lima T, da Conceição Viana Invenção M, Rosa Sales Leal L, Cristofer Flores Espinoza B, Silva de Macêdo L, do Nascimento Carvalho M, Jéssica Duarte Silva A, Carlos de Freitas A. An overview about biomarkers in breast cancer: Insights into the diagnostic and prognostic significance. Clin Chim Acta 2025; 567:120030. [PMID: 39515632 DOI: 10.1016/j.cca.2024.120030] [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] [Received: 04/30/2024] [Revised: 11/01/2024] [Accepted: 11/04/2024] [Indexed: 11/16/2024]
Abstract
Breast cancer (BC) is one of the most significant neoplasms globally due to its high incidence and mortality, particularly among females. As a highly heterogeneous pathology, biomarkers are essential for characterizing specific tumors. Currently, several biological processes are well-described in the context of this neoplasm, such as alterations in BRCA1/2, HER, and pathways involving estrogen and progesterone hormone receptors. These studies have enabled the use of these findings as more precise methods for diagnosis, prognosis, and treatment. However, beyond patients who do not exhibit these classic markers, some individuals within the same risk group respond differently to treatment. Therefore, the search for biological markers that can improve diagnosis, aid in stratification, or serve as therapeutic targets is continuous and urgent. Genetic signatures have led to molecular tests currently used in clinical practice, though certain limitations persist. Understanding genetic and epigenetic mechanisms facilitates the identification of potential biomarkers. Biomarker targets must undergo experimental and clinical trials on samples of significant size before reaching clinical utility. In this review, we compile the classical markers and describe the potential use of other markers associated with the biological processes of this neoplasm.
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Affiliation(s)
- Vanessa Emanuelle Pereira Santos
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco - Av. Prof. Moraes Rego, 1235. Cidade Universitária Recife, Pernambuco CEP: 50670-901, Brazil.
| | - Pedro Luiz de França Neto
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco - Av. Prof. Moraes Rego, 1235. Cidade Universitária Recife, Pernambuco CEP: 50670-901, Brazil.
| | - Beatriz Eda de Oliveira Isídio
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco - Av. Prof. Moraes Rego, 1235. Cidade Universitária Recife, Pernambuco CEP: 50670-901, Brazil.
| | - Pedro Henrique Bezerra Fontes
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco - Av. Prof. Moraes Rego, 1235. Cidade Universitária Recife, Pernambuco CEP: 50670-901, Brazil.
| | - Ingrid Andrêssa de Moura
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco - Av. Prof. Moraes Rego, 1235. Cidade Universitária Recife, Pernambuco CEP: 50670-901, Brazil.
| | - Bruna Isabel Santos Cruz
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco - Av. Prof. Moraes Rego, 1235. Cidade Universitária Recife, Pernambuco CEP: 50670-901, Brazil.
| | - Mylenna Máyra Gois de Sousa
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco - Av. Prof. Moraes Rego, 1235. Cidade Universitária Recife, Pernambuco CEP: 50670-901, Brazil.
| | - Daffany Luana Dos Santos
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco - Av. Prof. Moraes Rego, 1235. Cidade Universitária Recife, Pernambuco CEP: 50670-901, Brazil.
| | - Bianca de França São Marcos
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco - Av. Prof. Moraes Rego, 1235. Cidade Universitária Recife, Pernambuco CEP: 50670-901, Brazil.
| | - Samara Sousa de Pinho
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco - Av. Prof. Moraes Rego, 1235. Cidade Universitária Recife, Pernambuco CEP: 50670-901, Brazil.
| | - Beatriz Mendonça Alves Bandeira
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco - Av. Prof. Moraes Rego, 1235. Cidade Universitária Recife, Pernambuco CEP: 50670-901, Brazil.
| | - Stephanie Loureiro Leão
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco - Av. Prof. Moraes Rego, 1235. Cidade Universitária Recife, Pernambuco CEP: 50670-901, Brazil.
| | - Thainá de Almeida Lima
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco - Av. Prof. Moraes Rego, 1235. Cidade Universitária Recife, Pernambuco CEP: 50670-901, Brazil.
| | - Maria da Conceição Viana Invenção
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco - Av. Prof. Moraes Rego, 1235. Cidade Universitária Recife, Pernambuco CEP: 50670-901, Brazil.
| | - Lígia Rosa Sales Leal
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco - Av. Prof. Moraes Rego, 1235. Cidade Universitária Recife, Pernambuco CEP: 50670-901, Brazil.
| | - Benigno Cristofer Flores Espinoza
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco - Av. Prof. Moraes Rego, 1235. Cidade Universitária Recife, Pernambuco CEP: 50670-901, Brazil.
| | - Larissa Silva de Macêdo
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco - Av. Prof. Moraes Rego, 1235. Cidade Universitária Recife, Pernambuco CEP: 50670-901, Brazil.
| | - Matheus do Nascimento Carvalho
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco - Av. Prof. Moraes Rego, 1235. Cidade Universitária Recife, Pernambuco CEP: 50670-901, Brazil.
| | - Anna Jéssica Duarte Silva
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco - Av. Prof. Moraes Rego, 1235. Cidade Universitária Recife, Pernambuco CEP: 50670-901, Brazil.
| | - Antonio Carlos de Freitas
- Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco - Av. Prof. Moraes Rego, 1235. Cidade Universitária Recife, Pernambuco CEP: 50670-901, Brazil.
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15
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Asadzadeh A, Moattar FS, Moshfegh A. Predicting interactome networks of up/down regulated proteins and drug-gene interaction analysis associated with peri-implantitis. Dent Res J (Isfahan) 2025; 22:3. [PMID: 40028501 PMCID: PMC11870332 DOI: 10.4103/drj.drj_288_24] [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: 06/30/2024] [Revised: 10/29/2024] [Accepted: 11/04/2024] [Indexed: 03/05/2025] Open
Abstract
Background Peri-implantitis is implant-associated inflammation that leads to irreversible loss of surrounding bone. Early diagnosis increases the success of peri-implantitis treatment. Despite various studies associated with this most common complication, early detection of the onset of peri-implantitis remains a major challenge. Molecular biomarkers are applicable detectors for the early detection of numerous diseases and monitoring their development. The present study aimed to predict interactome networks of up/down regulated proteins and analyze drug-gene interaction in peri-implantitis to identify the diagnostic and druggable genes. Materials and Methods In this in silico study, a suitable gene expression profile related to peri-implantitis was retrieved from Gene Expression Omnibus. Screening differentially expressed genes (DEGs) was carried out based on the cut-off criteria |log2 (fold change)|>2 and P < 0.05. Interactome networks were constructed and analyzed by the STRING database (Version: 12.0) and the Cytoscape software (version: 3.9.1). Finally, to investigate drug-gene interaction, detected hub genes were analyzed by DGIdb (version: 5.0.6). Results A total of 216 genes were identified as DEGs (129 down-regulated and 87 up-regulated genes) in peri-implantitis. Regarding Cytoscape analysis, FCGR3B, CSF3R, AQP9, TREM1, and P2RY13 were the top 5 hub nodes of up-regulated DEGs, and CXCL10, OASL, IFIT1, RSAD2, and ISG15 were the top 5 hub nodes of down-regulated DEGs. Among these key nods, AQP9, CSF3R, CXCL10, IFIT1, ISG15, OASL, and, FCGR3B were therapeutic targets and had approved drugs. Conclusion In this research, seven genes have been identified as druggable genes in peri-implantitis which can be used to treat and diagnose this disease. However, these results and identified genes need to be validated by clinical or experimental methods.
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Affiliation(s)
- Azizeh Asadzadeh
- Department of Biology, Faculty of Science, Nour Danesh Institute of Higher Education, Meymeh, Isfahan, Iran
| | - Fatemeh Shams Moattar
- Department of Microbiology, Faculty of Basic Sciences, Lahijan Branch, Islamic Azad University, Lahijan, Iran
| | - Azam Moshfegh
- Department of Microbiology, Faculty of Basic Sciences, Lahijan Branch, Islamic Azad University, Lahijan, Iran
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16
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Siebels B, Moritz M, Hübler D, Gocke A, Riedner M, Voß H, Schlüter H. Assay for Characterizing Adsorption-Properties of Surfaces (APS). Chemistry 2024; 30:e202403000. [PMID: 39189660 PMCID: PMC11618038 DOI: 10.1002/chem.202403000] [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: 08/09/2024] [Accepted: 08/26/2024] [Indexed: 08/28/2024]
Abstract
Analytes, from sample preparation, until entering an analytical instrument, are prone to adsorb to surfaces, driven by the chemical properties of the surface and the liquids they are dissolved in. This problem can be addressed with internal standards when a single or few known analytes are quantified that are usually not available in omics. However, minimal to no loss of analytes is the aim. Here, we present a novel assay for qualifying and quantifying interactions responsible for adsorption of molecules to surfaces (APS) by using LC-MS/MS-based differential quantitative analysis. To reflect a broad range of chemical interactions with surfaces, a reference mixture of thousands of tryptic peptides, with known compositions was selected, representing a variety of different chemical characteristics. The assay was tested by investigating the adsorption properties of several different vials with different surface chemistries. A significant number of hydrophobic peptides adsorbed to conventional polypropylene vials. In contrast, only few peptides adsorbed to polypropylene vials, assigned as low-protein-binding. The highest number of peptides adsorbed to glass vials driven by electrostatic interactions. In summary, the new assay is suitable to characterize adsorption properties of different surfaces and to approximate the loss of analytes during sample preparation.
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Affiliation(s)
- Bente Siebels
- Section Mass Spectrometry and ProteomicsUniversity Medical Center Hamburg-EppendorfMartininstr. 52Hamburg20246Germany
| | - Manuela Moritz
- Section Mass Spectrometry and ProteomicsUniversity Medical Center Hamburg-EppendorfMartininstr. 52Hamburg20246Germany
| | | | - Antonia Gocke
- Section Mass Spectrometry and ProteomicsUniversity Medical Center Hamburg-EppendorfMartininstr. 52Hamburg20246Germany
| | - Maria Riedner
- Technology Platform Mass SpectrometryUniversity AdministrationUniversity of HamburgMittelweg 177Hamburg20148Germany
| | - Hannah Voß
- Section Mass Spectrometry and ProteomicsUniversity Medical Center Hamburg-EppendorfMartininstr. 52Hamburg20246Germany
| | - Hartmut Schlüter
- Section Mass Spectrometry and ProteomicsUniversity Medical Center Hamburg-EppendorfMartininstr. 52Hamburg20246Germany
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17
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Tirpak F, Hamilton LE, Schnabel RD, Sutovsky P. Biomarker-based high-throughput sperm phenotyping: Andrology in the age of precision medicine and agriculture. Anim Reprod Sci 2024; 271:107636. [PMID: 39522272 DOI: 10.1016/j.anireprosci.2024.107636] [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] [Received: 09/01/2024] [Revised: 10/25/2024] [Accepted: 11/07/2024] [Indexed: 11/16/2024]
Abstract
Reproductive efficiency is crucial for animal agriculture. This economically important aspect can be influenced by environmental burdens, nutritional imbalance, and gonadal or gametic malformations of genetic origin. Successful implementation of genomic-driven selective breeding in cattle depends on the reproductive performance of artificial insemination (AI) sires with valuable genomic production traits. Reproduction is traditionally viewed as a complex set of polygenic traits that are negatively impacted by using a small number of often closely related sires selected for AI due to their superior genetics. Despite recent progress, it remains difficult to define relationships between sire genome and variation in sperm phenotypes, even though several types of heritable, non-compensable sperm defects have been identified. In this review, we discuss the concept of sperm quality biomarker discovery and genomics of male fertility. We also outline a multidisciplinary genome-to-phenome approach for investigating heritable mutations and their impacts on bull fertility, sperm phenotypes and paternal contributions to early pregnancy. High-precision phenotyping requires novel, state-of-the-art instrumentation for sperm quality evaluation and development of new biomarkers of sperm quality in farm animals, with potential for incorporation into andrology-specific machine learning protocols and translation to human andrology. We conclude that reproduction is a complex phenotype that can be deciphered and explored for more precise male fertility evaluation and higher reproductive efficiency.
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Affiliation(s)
- Filip Tirpak
- Division of Animal Sciences, University of Missouri, Columbia, MO, USA
| | - Lauren E Hamilton
- Division of Animal Sciences, University of Missouri, Columbia, MO, USA
| | - Robert D Schnabel
- Division of Animal Sciences, University of Missouri, Columbia, MO, USA; Genetics Area Program, University of Missouri, Columbia, MO, USA
| | - Peter Sutovsky
- Division of Animal Sciences, University of Missouri, Columbia, MO, USA; Department of Obstetrics, Gynecology and Women's Health, University of Missouri, Columbia, MO, USA.
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18
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Sibomana O. Genetic Diversity Landscape in African Population: A Review of Implications for Personalized and Precision Medicine. Pharmgenomics Pers Med 2024; 17:487-496. [PMID: 39555236 PMCID: PMC11566596 DOI: 10.2147/pgpm.s485452] [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: 07/03/2024] [Accepted: 11/04/2024] [Indexed: 11/19/2024] Open
Abstract
Introduction Africa, a continent considered to be the cradle of human beings has the largest genetic diversity among its population than other continents. This review discusses the implications of this high African genetic diversity to the development of personalized and precision medicine. Methodology A comprehensive search across PubMed, Google Scholar, Science Direct, DOAJ, AJOL, and the Cochrane Library electronic databases and manual Google searches was conducted using key terms "genetics", "genetic diversity", "Africa", "precision medicine", and "personalized medicine". Updated original and review studies focusing on the implications of African high genetic diversity on personalized and precision medicine were included. Included studies were thematically synthesized to elucidate their positive or negative implications for personalized healthcare, aiming to foster informed clinical practice and scientific inquiry. Results African populations' high genetic diversity presents opportunities for personalized and precision medicine including improving pharmacogenomics, understanding gene interactions, discovering new variants, mapping disease genes, creating updated genomic reference panels, and validating biomarkers. However, challenges include underrepresentation in studies, scarcity of reference genomes, inaccuracy of genetic testing and interpretation, and ancestry misclassification. Addressing these requires the establishment of genomic research centers, increasing funding, creating biobanks and repositories, education, infrastructure, and international cooperation to enhance healthcare equity and outcomes through personalized and precision medicine. Conclusion High African genetic diversity presents both positive and negative implications for personalized and precision medicine. Deep further research is recommended to harness the challenges and use the opportunities to develop customized treatments.
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Affiliation(s)
- Olivier Sibomana
- Department of General Medicine and Surgery, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda
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19
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Ahmed S, Ahmed A, Rådegran G. Circulating biomarkers in pulmonary arterial hypertension: State-of-the-art review and future directions. JHLT OPEN 2024; 6:100152. [PMID: 40145036 PMCID: PMC11935499 DOI: 10.1016/j.jhlto.2024.100152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 03/28/2025]
Abstract
Pulmonary arterial hypertension is a complex and heterogeneous condition, associated with a considerable diagnostic delay, diminished exercise capacity, and poor outcomes. In pulmonary arterial hypertension, biomarker research has become a subject of intense inquiry, and novel circulating biomarkers acknowledged in a multitude of mechanistic pathways are emerging. Beyond the widely used natriuretic peptides, novel biomarkers may provide deeper pathophysiological understanding, support clinical decision-making, and prompt the incorporation of precision medicine by enabling a more precise individual phenotyping. In this state-of-the-art review, the recent advances in circulating biomarkers in pulmonary arterial hypertension from a clinical perspective are discussed, with particular emphasis on the current state of knowledge, gaps in evidence, and future perspectives.
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Affiliation(s)
- Salaheldin Ahmed
- Department of Clinical Sciences Lund, The Section for Cardiology, Lund University, Lund, Sweden
- The Haemodynamic Lab, The Section for Heart Failure and Valvular Disease, VO Heart and Lung Medicine, Skåne University Hospital, Lund, Sweden
- Department of Education and Research, Helsingborg Hospital, Helsingborg, Sweden
| | - Abdulla Ahmed
- Department of Clinical Sciences Lund, The Section for Cardiology, Lund University, Lund, Sweden
- The Haemodynamic Lab, The Section for Heart Failure and Valvular Disease, VO Heart and Lung Medicine, Skåne University Hospital, Lund, Sweden
- Department of Education and Research, Helsingborg Hospital, Helsingborg, Sweden
| | - Göran Rådegran
- Department of Clinical Sciences Lund, The Section for Cardiology, Lund University, Lund, Sweden
- The Haemodynamic Lab, The Section for Heart Failure and Valvular Disease, VO Heart and Lung Medicine, Skåne University Hospital, Lund, Sweden
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20
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Latosinska A, Frantzi M, Siwy J. Peptides as "better biomarkers"? Value, challenges, and potential solutions to facilitate implementation. MASS SPECTROMETRY REVIEWS 2024; 43:1195-1236. [PMID: 37357849 DOI: 10.1002/mas.21854] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 05/12/2023] [Accepted: 05/24/2023] [Indexed: 06/27/2023]
Abstract
Peptides carry important functions in normal physiological and pathophysiological processes and can serve as clinically useful biomarkers. Given the ability to diffuse passively across endothelial barriers, endogenous peptides can be examined in several body fluids, including among others urine, blood, and cerebrospinal fluid. This review article provides an update on the recently published literature that reports on investigating native peptides in body fluids using mass spectrometry-based platforms, specifically those studies that focus on the application of peptides as biomarkers to improve clinical management. We emphasize on the critical evaluation of their clinical value, how close they are to implementation, and the associated challenges and potential solutions to facilitate clinical implementation. During the last 5 years, numerous studies have been published, demonstrating the increased interest in mass spectrometry for the assessment of endogenous peptides as potential biomarkers. Importantly, the presence of few successful examples of implementation in patients' management and/or in the context of clinical trials indicates that the peptide biomarker field is evolving. Nevertheless, most studies still report evidence based on small sample size, while validation phases are frequently missing. Therefore, a gap between discovery and implementation still exists.
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Affiliation(s)
| | - Maria Frantzi
- Department of Biomarker Research, Mosaiques Diagnostics GmbH, Hannover, Germany
| | - Justyna Siwy
- Department of Biomarker Research, Mosaiques Diagnostics GmbH, Hannover, Germany
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21
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Cochran D, NourEldein M, Bezdekova D, Schram A, Howard R, Powers R. A Reproducibility Crisis for Clinical Metabolomics Studies. Trends Analyt Chem 2024; 180:117918. [PMID: 40236582 PMCID: PMC11999569 DOI: 10.1016/j.trac.2024.117918] [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] [Indexed: 01/03/2025]
Abstract
Cancer is a leading cause of world-wide death and a major subject of clinical studies focused on the identification of new diagnostic tools. An in-depth meta-analysis of 244 clinical metabolomics studies of human serum samples highlights a reproducibility crisis. A total of 2,206 unique metabolites were reported as statistically significant across the 244 studies, but 72% (1,582) of these metabolites were identified by only one study. Further analysis shows a random disparate disagreement in reported directions of metabolite concentration changes when detected by multiple studies. Statistical models revealed that 1,867 of the 2,206 metabolites (85%) are simply statistical noise. Only 3 to 12% of these metabolites reach the threshold of statistical significance for a specific cancer type. Our findings demonstrate the absence of a detectable metabolic response to cancer and provide evidence of a serious need by the metabolomics community to establish widely accepted best practices to improve future outcomes.
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Affiliation(s)
- Darcy Cochran
- Department of Chemistry, University of Nebraska-Lincoln, Lincoln, Nebraska, 68588-0304, USA
- Nebraska Center for Integrated Biomolecular Communication, University of Nebraska-Lincoln, Lincoln, Nebraska, 68588-0304, USA
| | - Mai NourEldein
- Department of Chemistry, University of Nebraska-Lincoln, Lincoln, Nebraska, 68588-0304, USA
- Nebraska Center for Integrated Biomolecular Communication, University of Nebraska-Lincoln, Lincoln, Nebraska, 68588-0304, USA
| | - Dominika Bezdekova
- Department of Chemistry, University of Nebraska-Lincoln, Lincoln, Nebraska, 68588-0304, USA
| | - Aaron Schram
- Department of Statistics, University of Nebraska – Lincoln, Lincoln, Nebraska, 68583-0963, USA
| | - Réka Howard
- Department of Statistics, University of Nebraska – Lincoln, Lincoln, Nebraska, 68583-0963, USA
| | - Robert Powers
- Department of Chemistry, University of Nebraska-Lincoln, Lincoln, Nebraska, 68588-0304, USA
- Nebraska Center for Integrated Biomolecular Communication, University of Nebraska-Lincoln, Lincoln, Nebraska, 68588-0304, USA
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22
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Onigbinde S, Gutierrez Reyes CD, Sandilya V, Chukwubueze F, Oluokun O, Sahioun S, Oluokun A, Mechref Y. Optimization of glycopeptide enrichment techniques for the identification of clinical biomarkers. Expert Rev Proteomics 2024; 21:431-462. [PMID: 39439029 PMCID: PMC11877277 DOI: 10.1080/14789450.2024.2418491] [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: 06/05/2024] [Revised: 07/28/2024] [Accepted: 10/11/2024] [Indexed: 10/25/2024]
Abstract
INTRODUCTION The identification and characterization of glycopeptides through LC-MS/MS and advanced enrichment techniques are crucial for advancing clinical glycoproteomics, significantly impacting the discovery of disease biomarkers and therapeutic targets. Despite progress in enrichment methods like Lectin Affinity Chromatography (LAC), Hydrophilic Interaction Liquid Chromatography (HILIC), and Electrostatic Repulsion Hydrophilic Interaction Chromatography (ERLIC), issues with specificity, efficiency, and scalability remain, impeding thorough analysis of complex glycosylation patterns crucial for disease understanding. AREAS COVERED This review explores the current challenges and innovative solutions in glycopeptide enrichment and mass spectrometry analysis, highlighting the importance of novel materials and computational advances for improving sensitivity and specificity. It outlines the potential future directions of these technologies in clinical glycoproteomics, emphasizing their transformative impact on medical diagnostics and therapeutic strategies. EXPERT OPINION The application of innovative materials such as Metal-Organic Frameworks (MOFs), Covalent Organic Frameworks (COFs), functional nanomaterials, and online enrichment shows promise in addressing challenges associated with glycoproteomics analysis by providing more selective and robust enrichment platforms. Moreover, the integration of artificial intelligence and machine learning is revolutionizing glycoproteomics by enhancing the processing and interpretation of extensive data from LC-MS/MS, boosting biomarker discovery, and improving predictive accuracy, thus supporting personalized medicine.
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Affiliation(s)
- Sherifdeen Onigbinde
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409, United States
| | | | - Vishal Sandilya
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409, United States
| | - Favour Chukwubueze
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409, United States
| | - Odunayo Oluokun
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409, United States
| | - Sarah Sahioun
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409, United States
| | - Ayobami Oluokun
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409, United States
| | - Yehia Mechref
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409, United States
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23
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Dorf N, Maciejczyk M. Skin senescence-from basic research to clinical practice. Front Med (Lausanne) 2024; 11:1484345. [PMID: 39493718 PMCID: PMC11527680 DOI: 10.3389/fmed.2024.1484345] [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: 08/21/2024] [Accepted: 10/09/2024] [Indexed: 11/05/2024] Open
Abstract
The most recognizable implications of tissue aging manifest themselves on the skin. Skin laxity, roughness, pigmentation disorders, age spots, wrinkles, telangiectasia or hair graying are symptoms of physiological aging. Development of the senescent phenotype depends on the interaction between aging cells and remodeling of the skin's extracellular matrix (ECM) that contains collagen and elastic fiber. Aging changes occur due to the combination of both endogenous (gene mutation, cellular metabolism or hormonal agents) and exogenous factors (ultraviolet light, environmental pollutants, and unsuitable diet). However, overproduction of mitochondrial reactive oxygen species (ROS) is a key factor driving cellular senescence. Aging theories have disclosed a range of diverse molecular mechanisms that are associated with cellular senescence of the body. Theories best supported by evidence include protein glycation, oxidative stress, telomere shortening, cell cycle arrest, and a limited number of cell divisions. Accumulation of the ECM damage is suggested to be a key factor in skin aging. Every cell indicates a functional and morphological change that may be used as a biomarker of senescence. Senescence-associated β-galactosidase (SA-β-gal), cell cycle inhibitors (p16INK4a, p21CIP1, p27, p53), DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS), senescence-associated heterochromatin foci (SAHF), shortening of telomeres or downregulation of lamina B1 constitute just an example of aging biomarkers known so far. Aging may also be assessed non-invasively through measuring the skin fluorescence of advanced glycation end-products (AGEs). This review summarizes the recent knowledge on the pathogenesis and clinical conditions of skin aging as well as biomarkers of skin senescence.
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Affiliation(s)
- Natalia Dorf
- Independent Laboratory of Cosmetology, Medical University of Białystok, Bialystok, Poland
| | - Mateusz Maciejczyk
- Department of Hygiene, Epidemiology and Ergonomics, Medical University of Białystok, Bialystok, Poland
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24
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Cuevas-González MV, Cuevas-González JC, Espinosa-Cristóbal LF, Tovar-Carrillo KL, Saucedo-Acuña RA, García-Calderón AG, Reyes-López SY, Zambrano-Galván G. The Potential of Gingival Crevicular Fluid as a Tool for Molecular Diagnosis: A Systematic Review. BIOMED RESEARCH INTERNATIONAL 2024; 2024:5560866. [PMID: 39445210 PMCID: PMC11496582 DOI: 10.1155/2024/5560866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 08/27/2024] [Accepted: 09/23/2024] [Indexed: 10/25/2024]
Abstract
A biomarker is defined as a characteristic that is measured as an indicator of a normal biological or pathological process, a response to an exposure or intervention. Biomarkers with a diagnostic approach must identify not only the presence but also the absence of the disease with high precision, so having the biological source of the said marker is of vital importance to ensure precision and accuracy; the aim was to carry out a review of its diagnostic potential. The search strategy was carried out in three databases: PubMed, ScienceDirect, and Scopus. The keywords that were used were as follows: "gingival crevicular fluid", "Biomarker", and "Diagnosis", using the Boolean operator "AND". The filter was used at 10 years. Within the type of molecules most studied, the cytokine family was the most abundant with 25.42% of the studies, followed by metalloproteinases and proteins with 16.9% each one. Studies that included RNA-type genetic material were less frequently found. As has been demonstrated, the use of GCF as a source of biomolecules for diagnostic use has been increasing, both for oral diseases, which reflects the local conditions of the disease; it also has the ability to reflect the development of distant diseases; and this is because GCF is a blood ultrafiltrate.
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Affiliation(s)
| | | | | | | | - Rosa Alicia Saucedo-Acuña
- Institute of Biomedical Sciences, Autonomous University of Ciudad Juarez, Juarez City, Chihuahua, Mexico
| | | | - Simón Yobanny Reyes-López
- Institute of Biomedical Sciences, Autonomous University of Ciudad Juarez, Juarez City, Chihuahua, Mexico
| | - Graciela Zambrano-Galván
- Research Division, Faculty of Medicine, Juarez University of the State of Durango, Durango City, Mexico
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25
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Yu B, Ma W. Biomarker discovery in hepatocellular carcinoma (HCC) for personalized treatment and enhanced prognosis. Cytokine Growth Factor Rev 2024; 79:29-38. [PMID: 39191624 DOI: 10.1016/j.cytogfr.2024.08.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 08/20/2024] [Indexed: 08/29/2024]
Abstract
Hepatocellular carcinoma (HCC) is a leading contributor to cancer-related deaths worldwide and presents significant challenges in diagnosis and treatment due to its heterogeneous nature. The discovery of biomarkers has become crucial in addressing these challenges, promising early detection, precise diagnosis, and personalized treatment plans. Key biomarkers, such as alpha fetoprotein (AFP) glypican 3 (GPC3) and des gamma carboxy prothrombin (DCP) have shown potential in improving clinical results. Progress in proteomic technologies, including next-generation sequencing (NGS), mass spectrometry, and liquid biopsies detecting circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), has deepened our understanding of HCC's molecular landscape. Immunological markers, like PD-L1 expression and tumor-infiltrating lymphocytes (TILs), also play a crucial role in guiding immunotherapy decisions. Despite these advancements, challenges remain in biomarker validation, standardization, integration into clinical practice, and cost-related barriers. Emerging technologies like single-cell sequencing and machine learning offer promising avenues for further exploration. Continued investment in research and collaboration among researchers, healthcare providers, and policymakers is vital to harness the potential of biomarkers fully, ultimately revolutionizing HCC management and improving patient outcomes through personalized treatment approaches.
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Affiliation(s)
- Baofa Yu
- Taimei Baofa Cancer Hospital, Dongping, Shandong 271500, China; Jinan Baofa Cancer Hospital, Jinan, Shandong 250000, China; Beijing Baofa Cancer Hospital, Beijing, 100010, China; Immune Oncology Systems, Inc, San Diego, CA 92102, USA.
| | - Wenxue Ma
- Department of Medicine, Sanford Stem Cell Institute, and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
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26
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Dakal TC, Dhakar R, Beura A, Moar K, Maurya PK, Sharma NK, Ranga V, Kumar A. Emerging methods and techniques for cancer biomarker discovery. Pathol Res Pract 2024; 262:155567. [PMID: 39232287 DOI: 10.1016/j.prp.2024.155567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 08/24/2024] [Accepted: 08/28/2024] [Indexed: 09/06/2024]
Abstract
Modern cancer research depends heavily on the identification and validation of biomarkers because they provide important information about the diagnosis, prognosis, and response to treatment of the cancer. This review will provide a comprehensive overview of cancer biomarkers, including their development phases and recent breakthroughs in transcriptomics and computational techniques for detecting these biomarkers. Blood-based biomarkers have great potential for non-invasive tumor dynamics and treatment response monitoring. These include circulating tumor DNA, exosomes, and microRNAs. Comprehensive molecular profiles are provided by multi-omic technologies, which combine proteomics, metabolomics, and genomes to support the identification of biomarkers and the targeting of therapeutic interventions. Genetic changes are detected by next-generation sequencing, and patterns of protein expression are found by protein arrays and mass spectrometry. Tumor heterogeneity and clonal evolution can be understood using metabolic profiling and single-cell studies. It is projected that the use of several biomarkers-genetic, protein, mRNA, microRNA, and DNA profiles, among others-will rise, enabling multi-biomarker analysis and improving individualised treatment plans. Biomarker identification and patient outcome prediction are further improved by developments in AI algorithms and imaging techniques. Robust biomarker validation and reproducibility require cooperation between industry, academia, and doctors. Biomarkers can provide individualized care, meet unmet clinical needs, and enhance patient outcomes despite some obstacles. Precision medicine will continue to take shape as scientific research advances and the integration of biomarkers with cutting-edge technologies continues to offer a more promising future for personalized cancer care.
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Affiliation(s)
- Tikam Chand Dakal
- Genome and Computational Biology Lab, Department of Biotechnology, Mohanlal Sukhadia University, Udaipur, Rajasthan 313001, India.
| | - Ramgopal Dhakar
- Deparment of Life Science, Mewar University, Chittorgarh, Rajasthan 312901, India
| | - Abhijit Beura
- Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka, India
| | - Kareena Moar
- Department of Biochemistry, Central University of Haryana, Mahendergarh, Haryana 123031, India
| | - Pawan Kumar Maurya
- Department of Biochemistry, Central University of Haryana, Mahendergarh, Haryana 123031, India
| | - Narendra Kumar Sharma
- Deparment of Bioscience and Biotechnology, Banasthali Vidyapith, Tonk, Rajasthan 304022, India
| | - Vipin Ranga
- DBT-NECAB, Assam Agriculture University, Jorhat, Assam 785013, India
| | - Abhishek Kumar
- Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka, India; Manipal Academy of Higher Education (MAHE) Manipal, Karnataka, India.
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27
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Llavanera M. Evaluation of sperm quality and male fertility: The use of molecular markers in boar sperm and seminal plasma. Anim Reprod Sci 2024; 269:107545. [PMID: 38960838 DOI: 10.1016/j.anireprosci.2024.107545] [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] [Received: 04/03/2024] [Revised: 06/26/2024] [Accepted: 06/27/2024] [Indexed: 07/05/2024]
Abstract
In pig production, the optimization of artificial insemination (AI) efficiency significantly relies on the accurate assessment of semen quality and fertility of boars. Traditional methods such as conventional seminogram techniques, although long-standing, exhibit limited sensitivity in predicting boar fertility, warranting the exploration of novel molecular markers. This review synthesizes the current knowledge on the utilization of molecular markers for semen quality evaluation and male fertility prediction in boars, providing an in-depth examination of molecular markers in this context. Specifically, the present work delves into the potential of OMICs technologies, encompassing genetic and genomic approaches, transcriptomics, proteomics, and metabolomics. A diverse array of molecular markers, including genomic regions associated with sperm quality and male fertility, chromatin integrity, mitochondrial DNA content, mRNA and non-coding RNA signatures, as well as proteins and metabolites in sperm and seminal plasma, are identified as promising molecular markers for fertility prediction in boars. Furthermore, the need of validating biomarkers and their practical implementation in AI centres is here emphasized. Addressing these considerations and integrating molecular markers within the swine breeding field holds the potential to enhance reproductive management practices and optimize productivity in boar breeding programs. This integration can significantly improve overall efficiency within the pig breeding industry.
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Affiliation(s)
- Marc Llavanera
- Laboratory of Chromosome Biology, Max Planck Institute of Biochemistry, Martinsried, Germany; Biotechnology of Animal and Human Reproduction (TechnoSperm), Institute of Food and Agricultural Technology, University of Girona, Girona, Spain.
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28
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Najdian A, Beiki D, Abbasi M, Gholamrezanezhad A, Ahmadzadehfar H, Amani AM, Ardestani MS, Assadi M. Exploring innovative strides in radiolabeled nanoparticle progress for multimodality cancer imaging and theranostic applications. Cancer Imaging 2024; 24:127. [PMID: 39304961 DOI: 10.1186/s40644-024-00762-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Accepted: 08/13/2024] [Indexed: 09/22/2024] Open
Abstract
Multimodal imaging unfolds as an innovative approach that synergistically employs a spectrum of imaging techniques either simultaneously or sequentially. The integration of computed tomography (CT), magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and optical imaging (OI) results in a comprehensive and complementary understanding of complex biological processes. This innovative approach combines the strengths of each method and overcoming their individual limitations. By harmoniously blending data from these modalities, it significantly improves the accuracy of cancer diagnosis and aids in treatment decision-making processes. Nanoparticles possess a high potential for facile functionalization with radioactive isotopes and a wide array of contrast agents. This strategic modification serves to augment signal amplification, significantly enhance image sensitivity, and elevate contrast indices. Such tailored nanoparticles constructs exhibit a promising avenue for advancing imaging modalities in both preclinical and clinical setting. Furthermore, nanoparticles function as a unified nanoplatform for the co-localization of imaging agents and therapeutic payloads, thereby optimizing the efficiency of cancer management strategies. Consequently, radiolabeled nanoparticles exhibit substantial potential in driving forward the realms of multimodal imaging and theranostic applications. This review discusses the potential applications of molecular imaging in cancer diagnosis, the utilization of nanotechnology-based radiolabeled materials in multimodal imaging and theranostic applications, as well as recent advancements in this field. It also highlights challenges including cytotoxicity and regulatory compliance, essential considerations for effective clinical translation of nanoradiopharmaceuticals in multimodal imaging and theranostic applications.
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Affiliation(s)
- Atena Najdian
- The Persian Gulf Nuclear Medicine Research Center, Bushehr Medical University Hospital, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran.
| | - Davood Beiki
- Research Center for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Milad Abbasi
- Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Gholamrezanezhad
- Department of Radiology, Keck School of Medicine, University of Southern California (USC), 1441 Eastlake Ave Ste 2315, Los Angeles, CA, 90089, USA
| | - Hojjat Ahmadzadehfar
- Department of Nuclear Medicine, Klinikum Westfalen, Dortmund, Germany
- Department of Nuclear Medicine, Institute of Radiology, Neuroradiology and Nuclear Medicine, University Hospital Knappschaftskrankenhaus, Bochum, Germany
| | - Ali Mohammad Amani
- Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Mehdi Shafiee Ardestani
- Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
| | - Majid Assadi
- The Persian Gulf Nuclear Medicine Research Center, Bushehr Medical University Hospital, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
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29
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Siahaan AMP, Ivander A, Tandean S, Indharty RS, Fernando ET, Nugroho SA, Milenia V, Az Zahra DO. Unlocking the Diagnostic Potential: A Systematic Review of Biomarkers in Spinal Tuberculosis. J Clin Med 2024; 13:5028. [PMID: 39274240 PMCID: PMC11396406 DOI: 10.3390/jcm13175028] [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: 07/08/2024] [Revised: 08/13/2024] [Accepted: 08/23/2024] [Indexed: 09/16/2024] Open
Abstract
Background/Objectives: Spinal tuberculosis (STB) is frequently misdiagnosed due to the multitude of symptoms it presents with. This review aimed to investigate the biomarkers that have the potential to accurately diagnose spinal TB in its early stages. Methods: A systematic search was conducted across multiple databases, yielding a diverse range of biomarkers categorized into complete blood count parameters, host inflammatory responses, bacterial antigens, and RNA-based markers. This review included studies on spinal tuberculosis patients, including blood serum biomarkers, while exclusion criteria included pediatric cases, cerebrospinal fluid or imaging biomarkers, co-infection with other bacteria, viruses, comorbidities, tumors, immune diseases, HIV infection, metabolic disorders, animal studies, opinion papers, and biomarkers relevant to health problems outside the disease. QUADAS-2 was used as a quality assessment tool for this review. This review identifies several promising biomarkers with significant diagnostic potential. Results: The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), IFN-γ, CXCR3, CXCL9, CXCL10, PSMB9, STAT1, TAP1, and specific miRNA combinations demonstrated noteworthy diagnostic accuracy in distinguishing STB from other spinal pathologies. Additionally, these biomarkers offer insights into disease severity and progression. The review also highlighted the importance of combining multiple biomarkers to enhance diagnostic precision. This comprehensive systematic review underscores the potential of biomarkers to revolutionize the diagnosis of spinal tuberculosis. By integrating these markers into clinical practice, healthcare providers can achieve earlier and more accurate diagnosis, leading to improved patient care and outcomes. Conclusions: The combination of multiple biomarkers, including NLR, PSMB9, STAT1, and specific miRNAs, demonstrates promising diagnostic accuracy.
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Affiliation(s)
| | - Alvin Ivander
- Center of Evidence Based Medicine, Faculty of Medicine, Universitas Sumatera Utara, Medan 20155, Indonesia
| | - Steven Tandean
- Department of Neurosurgery, Faculty of Medicine, Universitas Sumatera Utara, Medan 20155, Indonesia
| | - Rr Suzy Indharty
- Department of Neurosurgery, Faculty of Medicine, Universitas Sumatera Utara, Medan 20155, Indonesia
| | - Eric Teo Fernando
- Center of Evidence Based Medicine, Faculty of Medicine, Universitas Sumatera Utara, Medan 20155, Indonesia
| | - Stefanus Adi Nugroho
- Center of Evidence Based Medicine, Faculty of Medicine, Universitas Sumatera Utara, Medan 20155, Indonesia
| | - Viria Milenia
- Center of Evidence Based Medicine, Faculty of Medicine, Universitas Sumatera Utara, Medan 20155, Indonesia
| | - Dhea Olivia Az Zahra
- Center of Evidence Based Medicine, Faculty of Medicine, Universitas Sumatera Utara, Medan 20155, Indonesia
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30
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Dejardin D, Kraxner A, Schindler E, Städler N, Wolbers M. An overview of statistical methods for biomarkers relevant to early clinical development of cancer immunotherapies. Front Immunol 2024; 15:1351584. [PMID: 39234243 PMCID: PMC11371698 DOI: 10.3389/fimmu.2024.1351584] [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] [Received: 12/06/2023] [Accepted: 07/29/2024] [Indexed: 09/06/2024] Open
Abstract
Over the last decade, a new paradigm for cancer therapies has emerged which leverages the immune system to act against the tumor. The novel mechanism of action of these immunotherapies has also introduced new challenges to drug development. Biomarkers play a key role in several areas of early clinical development of immunotherapies including the demonstration of mechanism of action, dose finding and dose optimization, mitigation and prevention of adverse reactions, and patient enrichment and indication prioritization. We discuss statistical principles and methods for establishing the prognostic, predictive aspect of a (set of) biomarker and for linking the change in biomarkers to clinical efficacy in the context of early development studies. The methods discussed are meant to avoid bias and produce robust and reproducible conclusions. This review is targeted to drug developers and data scientists interested in the strategic usage and analysis of biomarkers in the context of immunotherapies.
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Affiliation(s)
- David Dejardin
- Data Sciences, Product Development, F. Hoffmann-La Roche AG, Basel, Switzerland
| | - Anton Kraxner
- Roche Pharma Research and Early Development Oncology, F. Hoffmann-La Roche AG, Basel, Switzerland
| | - Emilie Schindler
- Roche Pharma Research and Early Development Oncology, F. Hoffmann-La Roche AG, Basel, Switzerland
| | - Nicolas Städler
- Roche Pharma Research and Early Development Oncology, F. Hoffmann-La Roche AG, Basel, Switzerland
| | - Marcel Wolbers
- Data Sciences, Product Development, F. Hoffmann-La Roche AG, Basel, Switzerland
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31
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Li Z, Hu Y, Wang W, Zou F, Yang J, Gao W, Feng S, Chen G, Shi C, Cai Y, Deng G, Chen X. Integrating pathogen- and host-derived blood biomarkers for enhanced tuberculosis diagnosis: a comprehensive review. Front Immunol 2024; 15:1438989. [PMID: 39185416 PMCID: PMC11341448 DOI: 10.3389/fimmu.2024.1438989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Accepted: 07/24/2024] [Indexed: 08/27/2024] Open
Abstract
This review explores the evolving landscape of blood biomarkers in the diagnosis of tuberculosis (TB), focusing on biomarkers derived both from the pathogen and the host. These biomarkers provide critical insights that can improve diagnostic accuracy and timeliness, essential for effective TB management. The document highlights recent advancements in molecular techniques that have enhanced the detection and characterization of specific biomarkers. It also discusses the integration of these biomarkers into clinical practice, emphasizing their potential to revolutionize TB diagnostics by enabling more precise detection and monitoring of the disease progression. Challenges such as variability in biomarker expression and the need for standardized validation processes are addressed to ensure reliability across different populations and settings. The review calls for further research to refine these biomarkers and fully harness their potential in the fight against TB, suggesting a multidisciplinary approach to overcome existing barriers and optimize diagnostic strategies. This comprehensive analysis underscores the significance of blood biomarkers as invaluable tools in the global effort to control and eliminate TB.
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Affiliation(s)
- Zhaodong Li
- Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen, China
- Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, China
| | - Yunlong Hu
- Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen, China
| | - Wenfei Wang
- National Clinical Research Center for Infectious Disease, The Third People's Hospital of Shenzhen, Southern University of Science and Technology, Shenzhen, China
| | - Fa Zou
- Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen, China
| | - Jing Yang
- Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen, China
| | - Wei Gao
- Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen, China
| | - SiWan Feng
- Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen, China
| | - Guanghuan Chen
- Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen, China
| | - Chenyan Shi
- Department of Preventive Medicine, School of Public Health, Shenzhen University, Shenzhen, China
| | - Yi Cai
- Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen, China
| | - Guofang Deng
- Guangdong Key Lab for Diagnosis & Treatment of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, China
| | - Xinchun Chen
- Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen, China
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Ferrito N, Báez-Flores J, Rodríguez-Martín M, Sastre-Rodríguez J, Coppola A, Isidoro-García M, Prieto-Matos P, Lacal J. Biomarker Landscape in RASopathies. Int J Mol Sci 2024; 25:8563. [PMID: 39201250 PMCID: PMC11354534 DOI: 10.3390/ijms25168563] [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: 07/06/2024] [Revised: 07/28/2024] [Accepted: 08/02/2024] [Indexed: 09/02/2024] Open
Abstract
RASopathies are a group of related genetic disorders caused by mutations in genes within the RAS/MAPK signaling pathway. This pathway is crucial for cell division, growth, and differentiation, and its disruption can lead to a variety of developmental and health issues. RASopathies present diverse clinical features and pose significant diagnostic and therapeutic challenges. Studying the landscape of biomarkers in RASopathies has the potential to improve both clinical practices and the understanding of these disorders. This review provides an overview of recent discoveries in RASopathy molecular profiling, which extend beyond traditional gene mutation analysis. mRNAs, non-coding RNAs, protein expression patterns, and post-translational modifications characteristic of RASopathy patients within pivotal signaling pathways such as the RAS/MAPK, PI3K/AKT/mTOR, and Rho/ROCK/LIMK2/cofilin pathways are summarized. Additionally, the field of metabolomics holds potential for uncovering metabolic signatures associated with specific RASopathies, which are crucial for developing precision medicine. Beyond molecular markers, we also examine the role of histological characteristics and non-invasive physiological assessments in identifying potential biomarkers, as they provide evidence of the disease's effects on various systems. Here, we synthesize key findings and illuminate promising avenues for future research in RASopathy biomarker discovery, underscoring rigorous validation and clinical translation.
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Affiliation(s)
- Noemi Ferrito
- Laboratory of Functional Genetics of Rare Diseases, Department of Microbiology and Genetics, University of Salamanca (USAL), 37007 Salamanca, Spain; (N.F.); (J.B.-F.); (J.S.-R.); (A.C.)
- GIR of Biomedicine of Rare Diseases, University of Salamanca (USAL), 37007 Salamanca, Spain;
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain;
| | - Juan Báez-Flores
- Laboratory of Functional Genetics of Rare Diseases, Department of Microbiology and Genetics, University of Salamanca (USAL), 37007 Salamanca, Spain; (N.F.); (J.B.-F.); (J.S.-R.); (A.C.)
- GIR of Biomedicine of Rare Diseases, University of Salamanca (USAL), 37007 Salamanca, Spain;
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain;
| | - Mario Rodríguez-Martín
- Laboratory of Functional Genetics of Rare Diseases, Department of Microbiology and Genetics, University of Salamanca (USAL), 37007 Salamanca, Spain; (N.F.); (J.B.-F.); (J.S.-R.); (A.C.)
- GIR of Biomedicine of Rare Diseases, University of Salamanca (USAL), 37007 Salamanca, Spain;
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain;
| | - Julián Sastre-Rodríguez
- Laboratory of Functional Genetics of Rare Diseases, Department of Microbiology and Genetics, University of Salamanca (USAL), 37007 Salamanca, Spain; (N.F.); (J.B.-F.); (J.S.-R.); (A.C.)
| | - Alessio Coppola
- Laboratory of Functional Genetics of Rare Diseases, Department of Microbiology and Genetics, University of Salamanca (USAL), 37007 Salamanca, Spain; (N.F.); (J.B.-F.); (J.S.-R.); (A.C.)
- GIR of Biomedicine of Rare Diseases, University of Salamanca (USAL), 37007 Salamanca, Spain;
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain;
| | - María Isidoro-García
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain;
- Clinical Biochemistry Department, University Hospital of Salamanca, 37007 Salamanca, Spain
- Clinical Rare Diseases Reference Unit DiERCyL, 37007 Castilla y León, Spain
- Department of Medicine, University of Salamanca (USAL), 37007 Salamanca, Spain
| | - Pablo Prieto-Matos
- GIR of Biomedicine of Rare Diseases, University of Salamanca (USAL), 37007 Salamanca, Spain;
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain;
- Department of Pediatrics, University Hospital of Salamanca, 37007 Salamanca, Spain
- Department of Biomedical and Diagnostics Science, University of Salamanca (USAL), 37007 Salamanca, Spain
| | - Jesus Lacal
- Laboratory of Functional Genetics of Rare Diseases, Department of Microbiology and Genetics, University of Salamanca (USAL), 37007 Salamanca, Spain; (N.F.); (J.B.-F.); (J.S.-R.); (A.C.)
- GIR of Biomedicine of Rare Diseases, University of Salamanca (USAL), 37007 Salamanca, Spain;
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain;
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Goswami M, Toney NJ, Pitts SC, Celades C, Schlom J, Donahue RN. Peripheral immune biomarkers for immune checkpoint inhibition of solid tumours. Clin Transl Med 2024; 14:e1814. [PMID: 39162097 PMCID: PMC11333946 DOI: 10.1002/ctm2.1814] [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: 05/30/2024] [Revised: 07/29/2024] [Accepted: 08/04/2024] [Indexed: 08/21/2024] Open
Abstract
BACKGROUND With the rapid adoption of immunotherapy for the treatment of cancer comes the pressing need for readily accessible biomarkers to guide immunotherapeutic strategies and offer insights into outcomes with specific treatments. Regular sampling of solid tumour tissues outside of melanoma for immune monitoring is not often feasible; conversely, routine, frequent interrogation of circulating immune biomarkers is entirely possible. As immunotherapies and immune checkpoint inhibitors, in particular, are more widely used in first-line, neoadjuvant, and metastatic settings, the discovery and validation of peripheral immune biomarkers are urgently needed across solid tumour types for improved prediction and prognostication of clinical outcomes in response to immunotherapy, as well as elucidation of mechanistic underpinnings of the intervention. Careful experimental design, encompassing both retrospective and prospective studies, is required in such biomarker identification studies, and concerted efforts are essential for their advancement into clinical settings. CONCLUSION In this review, we summarize shared immune features between the tumour microenvironment and systemic circulation, evaluate exploratory peripheral immune biomarker studies, and discuss associations between candidate biomarkers with clinical outcomes. We also consider integration of multiple peripheral immune parameters for better prediction and prognostication and discuss considerations in study design to further evaluate the clinical utility of candidate peripheral immune biomarkers for immunotherapy of solid tumours. HIGHLIGHTS Peripheral immune biomarkers are critical for improved prediction and prognostication of clinical outcomes for patients with solid tumours treated with immune checkpoint inhibition. Candidate peripheral biomarkers, such as cytokines, soluble factors, and immune cells, have potential as biomarkers to guide immunotherapy of solid tumours. Multiple peripheral immune parameters may be integrated to improve prediction and prognostication. The potential of peripheral immune biomarkers to guide immunotherapy of solid tumours requires critical work in biomarker discovery, validation, and standardization.
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Affiliation(s)
- Meghali Goswami
- Center for Immuno‐Oncology, Center for Cancer Research, National Cancer InstituteNational Institutes of HealthBethesdaMarylandUSA
| | - Nicole J. Toney
- Center for Immuno‐Oncology, Center for Cancer Research, National Cancer InstituteNational Institutes of HealthBethesdaMarylandUSA
| | - Stephanie C. Pitts
- Center for Immuno‐Oncology, Center for Cancer Research, National Cancer InstituteNational Institutes of HealthBethesdaMarylandUSA
| | - Carolina Celades
- Center for Immuno‐Oncology, Center for Cancer Research, National Cancer InstituteNational Institutes of HealthBethesdaMarylandUSA
| | - Jeffrey Schlom
- Center for Immuno‐Oncology, Center for Cancer Research, National Cancer InstituteNational Institutes of HealthBethesdaMarylandUSA
| | - Renee N. Donahue
- Center for Immuno‐Oncology, Center for Cancer Research, National Cancer InstituteNational Institutes of HealthBethesdaMarylandUSA
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García de Yébenes Prous MJ, Carmona Ortells L. Biomarkers: how to consolidate them in clinical practice. REUMATOLOGIA CLINICA 2024; 20:386-391. [PMID: 39004560 DOI: 10.1016/j.reumae.2024.07.002] [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: 02/14/2024] [Accepted: 05/20/2024] [Indexed: 07/16/2024]
Abstract
An inadequate biomarker validation can affect many patients' diagnosis, treatment, and follow-up. Therefore, special interest should be placed on performing these analyses correctly so that biomarkers can be applicable to patients and evidence of their clinical usefulness can be generated. A methodological work on the concept of biomarkers is presented, as well as the difficulties associated with the methodological approach to their development, validation, and implementation in clinical practice.
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Yu D, Kane MJ, Koay EJ, Wistuba II, Hobbs BP. Machine learning identifies prognostic subtypes of the tumor microenvironment of NSCLC. Sci Rep 2024; 14:15004. [PMID: 38951567 PMCID: PMC11217297 DOI: 10.1038/s41598-024-64977-7] [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] [Received: 02/21/2024] [Accepted: 06/14/2024] [Indexed: 07/03/2024] Open
Abstract
The tumor microenvironment (TME) plays a fundamental role in tumorigenesis, tumor progression, and anti-cancer immunity potential of emerging cancer therapeutics. Understanding inter-patient TME heterogeneity, however, remains a challenge to efficient drug development. This article applies recent advances in machine learning (ML) for survival analysis to a retrospective study of NSCLC patients who received definitive surgical resection and immune pathology following surgery. ML methods are compared for their effectiveness in identifying prognostic subtypes. Six survival models, including Cox regression and five survival machine learning methods, were calibrated and applied to predict survival for NSCLC patients based on PD-L1 expression, CD3 expression, and ten baseline patient characteristics. Prognostic subregions of the biomarker space are delineated for each method using synthetic patient data augmentation and compared between models for overall survival concordance. A total of 423 NSCLC patients (46% female; median age [inter quantile range]: 67 [60-73]) treated with definite surgical resection were included in the study. And 219 (52%) patients experienced events during the observation period consisting of a maximum follow-up of 10 years and median follow up 78 months. The random survival forest (RSF) achieved the highest predictive accuracy, with a C-index of 0.84. The resultant biomarker subtypes demonstrate that patients with high PD-L1 expression combined with low CD3 counts experience higher risk of death within five-years of surgical resection.
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Affiliation(s)
- Duo Yu
- Division of Biostatistics, Institute for Health & Equity, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Michael J Kane
- Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA
| | - Eugene J Koay
- Department Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ignacio I Wistuba
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Brian P Hobbs
- Department of Population Health, Dell Medical School, The University of Texas at Austin, 1601 Trinity St., Austin, TX, 78712, USA.
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Jóźwiak K, Nguyen VH, Sollfrank L, Linn SC, Hauptmann M. Cox proportional hazards regression in small studies of predictive biomarkers. Sci Rep 2024; 14:14232. [PMID: 38902269 PMCID: PMC11190253 DOI: 10.1038/s41598-024-64573-9] [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: 11/03/2023] [Accepted: 06/11/2024] [Indexed: 06/22/2024] Open
Abstract
Predictive biomarkers are essential for personalized medicine since they select the best treatment for a specific patient. However, of all biomarkers that are evaluated, only few are eventually used in clinical practice. Many promising biomarkers may be erroneously abandoned because they are investigated in small studies using standard statistical techniques which can cause small sample bias or lack of power. The standard technique for failure time endpoints is Cox proportional hazards regression with a multiplicative interaction term between binary variables of biomarker and treatment. Properties of this model in small studies have not been evaluated so far, therefore we performed a simulation study to understand its small sample behavior. As a remedy, we applied a Firth correction to the score function of the Cox model and obtained confidence intervals (CI) using a profile likelihood (PL) approach. These methods are generally recommended for small studies of different design. Our results show that a Cox model estimates the biomarker-treatment interaction term and the treatment effect in one of the biomarker subgroups with bias, and overestimates their standard errors. Bias is however reduced and power is increased with Firth correction and PL CIs. Hence, the modified Cox model and PL CI should be used instead of a standard Cox model with Wald based CI in small studies of predictive biomarkers.
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Affiliation(s)
- K Jóźwiak
- Institute of Biostatistics and Registry Research, Brandenburg Medical School Theodor Fontane, Fehrbelliner Straße 39, 16816, Neuruppin, Germany.
| | - V H Nguyen
- Institute of Biostatistics and Registry Research, Brandenburg Medical School Theodor Fontane, Fehrbelliner Straße 39, 16816, Neuruppin, Germany
- Leibniz Centre for Agricultural Landscape Research (ZALF), Müncheberg, Germany
| | - L Sollfrank
- Institute of Biostatistics and Registry Research, Brandenburg Medical School Theodor Fontane, Fehrbelliner Straße 39, 16816, Neuruppin, Germany
| | - S C Linn
- Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
- Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
- Department of Pathology, University Medical Center, Utrecht, The Netherlands
| | - M Hauptmann
- Institute of Biostatistics and Registry Research, Brandenburg Medical School Theodor Fontane, Fehrbelliner Straße 39, 16816, Neuruppin, Germany
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Al-Husinat L, Azzam S, Al Sharie S, Al Sharie AH, Battaglini D, Robba C, Marini JJ, Thornton LT, Cruz FF, Silva PL, Rocco PRM. Effects of mechanical ventilation on the interstitial extracellular matrix in healthy lungs and lungs affected by acute respiratory distress syndrome: a narrative review. Crit Care 2024; 28:165. [PMID: 38750543 PMCID: PMC11094887 DOI: 10.1186/s13054-024-04942-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 05/06/2024] [Indexed: 05/19/2024] Open
Abstract
BACKGROUND Mechanical ventilation, a lifesaving intervention in critical care, can lead to damage in the extracellular matrix (ECM), triggering inflammation and ventilator-induced lung injury (VILI), particularly in conditions such as acute respiratory distress syndrome (ARDS). This review discusses the detailed structure of the ECM in healthy and ARDS-affected lungs under mechanical ventilation, aiming to bridge the gap between experimental insights and clinical practice by offering a thorough understanding of lung ECM organization and the dynamics of its alteration during mechanical ventilation. MAIN TEXT Focusing on the clinical implications, we explore the potential of precise interventions targeting the ECM and cellular signaling pathways to mitigate lung damage, reduce inflammation, and ultimately improve outcomes for critically ill patients. By analyzing a range of experimental studies and clinical papers, particular attention is paid to the roles of matrix metalloproteinases (MMPs), integrins, and other molecules in ECM damage and VILI. This synthesis not only sheds light on the structural changes induced by mechanical stress but also underscores the importance of cellular responses such as inflammation, fibrosis, and excessive activation of MMPs. CONCLUSIONS This review emphasizes the significance of mechanical cues transduced by integrins and their impact on cellular behavior during ventilation, offering insights into the complex interactions between mechanical ventilation, ECM damage, and cellular signaling. By understanding these mechanisms, healthcare professionals in critical care can anticipate the consequences of mechanical ventilation and use targeted strategies to prevent or minimize ECM damage, ultimately leading to better patient management and outcomes in critical care settings.
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Affiliation(s)
- Lou'i Al-Husinat
- Department of Clinical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan
| | - Saif Azzam
- Faculty of Medicine, Yarmouk University, Irbid, Jordan
| | | | - Ahmed H Al Sharie
- Department of Pathology and Microbiology, Jordan University of Science and Technology, Irbid, Jordan
| | - Denise Battaglini
- Anesthesia and Intensive Care, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Chiara Robba
- Anesthesia and Intensive Care, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Dipartimento di Scienze Chirurgiche e Diagnostiche, Università Degli Studi di Genova, Genoa, Italy
| | - John J Marini
- Department of Pulmonary and Critical Care Medicine, University of Minnesota, Minneapolis, St Paul, MN, USA
| | - Lauren T Thornton
- Department of Pulmonary and Critical Care Medicine, University of Minnesota, Minneapolis, St Paul, MN, USA
| | - Fernanda F Cruz
- Laboratory of Pulmonary Investigation, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Pedro L Silva
- Laboratory of Pulmonary Investigation, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Patricia R M Rocco
- Laboratory of Pulmonary Investigation, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
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He K, Baniasad M, Kwon H, Caval T, Xu G, Lebrilla C, Hommes DW, Bertozzi C. Decoding the glycoproteome: a new frontier for biomarker discovery in cancer. J Hematol Oncol 2024; 17:12. [PMID: 38515194 PMCID: PMC10958865 DOI: 10.1186/s13045-024-01532-x] [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] [Received: 12/02/2023] [Accepted: 03/04/2024] [Indexed: 03/23/2024] Open
Abstract
Cancer early detection and treatment response prediction continue to pose significant challenges. Cancer liquid biopsies focusing on detecting circulating tumor cells (CTCs) and DNA (ctDNA) have shown enormous potential due to their non-invasive nature and the implications in precision cancer management. Recently, liquid biopsy has been further expanded to profile glycoproteins, which are the products of post-translational modifications of proteins and play key roles in both normal and pathological processes, including cancers. The advancements in chemical and mass spectrometry-based technologies and artificial intelligence-based platforms have enabled extensive studies of cancer and organ-specific changes in glycans and glycoproteins through glycomics and glycoproteomics. Glycoproteomic analysis has emerged as a promising tool for biomarker discovery and development in early detection of cancers and prediction of treatment efficacy including response to immunotherapies. These biomarkers could play a crucial role in aiding in early intervention and personalized therapy decisions. In this review, we summarize the significant advance in cancer glycoproteomic biomarker studies and the promise and challenges in integration into clinical practice to improve cancer patient care.
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Affiliation(s)
- Kai He
- James Comprehensive Cancer Center, The Ohio State University, Columbus, USA.
| | | | - Hyunwoo Kwon
- James Comprehensive Cancer Center, The Ohio State University, Columbus, USA
| | | | - Gege Xu
- InterVenn Biosciences, South San Francisco, USA
| | - Carlito Lebrilla
- Department of Biochemistry and Molecular Medicine, UC Davis Health, Sacramento, USA
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Gillan R, Bachtel G, Webber K, Ezzair Y, Myers NE, Bishayee A. Osteopathic manipulative treatment for chronic inflammatory diseases. J Evid Based Med 2024; 17:172-186. [PMID: 38488211 DOI: 10.1111/jebm.12590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Accepted: 02/25/2024] [Indexed: 04/02/2024]
Abstract
Chronic inflammatory diseases (CIDs) are debilitating and potentially lethal illnesses that affect a large proportion of the global population. Osteopathic manipulative treatment (OMT) is a manual therapy technique developed and performed by osteopathic physicians that facilitates the body's innate healing processes. Therefore, OMT may prove a beneficial anti-inflammatory modality useful in the management and treatment of CIDs. This work aims to objectively evaluate the therapeutic benefits of OMT in patients with various CIDs. In this review, a structured literature search was performed. The included studies involving asthma, chronic obstructive pulmonary disease, irritable bowel syndrome, ankylosing spondylitis, and peripheral arterial disease were selected for this work. Various OMT modalities, including lymphatic, still, counterstain, and muscle energy techniques, were utilized. Control treatments included sham techniques, routine care, or no treatment. OMT utilization led to variable patient outcomes in individuals with pathologies linked to CID.
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Affiliation(s)
- Ross Gillan
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Gabrielle Bachtel
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Kassidy Webber
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Yasmine Ezzair
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Nicole E Myers
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
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40
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Ferro A, Saccu G, Mattivi S, Gaido A, Herrera Sanchez MB, Haque S, Silengo L, Altruda F, Durazzo M, Fagoonee S. Extracellular Vesicles as Delivery Vehicles for Non-Coding RNAs: Potential Biomarkers for Chronic Liver Diseases. Biomolecules 2024; 14:277. [PMID: 38540698 PMCID: PMC10967855 DOI: 10.3390/biom14030277] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 02/15/2024] [Accepted: 02/21/2024] [Indexed: 01/03/2025] Open
Abstract
In recent years, EVs have emerged as promising vehicles for coding and non-coding RNAs (ncRNAs), which have demonstrated remarkable potential as biomarkers for various diseases, including chronic liver diseases (CLDs). EVs are small, membrane-bound particles released by cells, carrying an arsenal of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and other ncRNA species, such as piRNAs, circRNAs, and tsRNAs. These ncRNAs act as key regulators of gene expression, splicing, and translation, providing a comprehensive molecular snapshot of the cells of origin. The non-invasive nature of EV sampling, typically via blood or serum collection, makes them highly attractive candidates for clinical biomarker applications. Moreover, EV-encapsulated ncRNAs offer unique advantages over traditional cell-free ncRNAs due to their enhanced stability within the EVs, hence allowing for their detection in circulation for extended periods and enabling more sensitive and reliable biomarker measurements. Numerous studies have investigated the potential of EV-enclosed ncRNAs as biomarkers for CLD. MiRNAs, in particular, have gained significant attention due to their ability to rapidly respond to changes in cellular stress and inflammation, hallmarks of CLD pathogenesis. Elevated levels of specific miRNAs have been consistently associated with various CLD subtypes, including metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), and chronic hepatitis B and C. LncRNAs have also emerged as promising biomarkers for CLD. These transcripts are involved in a wide range of cellular processes, including liver regeneration, fibrosis, and cancer progression. Studies have shown that lncRNA expression profiles can distinguish between different CLD subtypes, providing valuable insights into disease progression and therapeutic response. Promising EV-enclosed ncRNA biomarkers for CLD included miR-122 (elevated levels of miR-122 are associated with MASLD progression and liver fibrosis), miR-21 (increased expression of miR-21 is linked to liver inflammation and fibrosis in CLD patients), miR-192 (elevated levels of miR-192 are associated with more advanced stages of CLD, including cirrhosis and HCC), LncRNA HOTAIR (increased HOTAIR expression is associated with MASLD progression and MASH development), and LncRNA H19 (dysregulation of H19 expression is linked to liver fibrosis and HCC progression). In the present review, we focus on the EV-enclosed ncRNAs as promising tools for the diagnosis and monitoring of CLD of various etiologies.
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Affiliation(s)
- Arianna Ferro
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (A.F.); (G.S.); (S.M.); (A.G.); (M.D.)
| | - Gabriele Saccu
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (A.F.); (G.S.); (S.M.); (A.G.); (M.D.)
| | - Simone Mattivi
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (A.F.); (G.S.); (S.M.); (A.G.); (M.D.)
| | - Andrea Gaido
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (A.F.); (G.S.); (S.M.); (A.G.); (M.D.)
| | - Maria Beatriz Herrera Sanchez
- 2i3T, Società per la Gestione Dell’incubatore di Imprese e per il Trasferimento Tecnologico, University of Torino, 10126 Turin, Italy;
- Molecular Biotechnology Centre “Guido Tarone”, 10126 Turin, Italy; (L.S.); (F.A.)
| | - Shafiul Haque
- Research and Scientific Studies Unit, College of Nursing and Health Sciences, Jazan University, Jazan 45142, Saudi Arabia;
- Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman 13306, United Arab Emirates
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut 1102 2801, Lebanon
| | - Lorenzo Silengo
- Molecular Biotechnology Centre “Guido Tarone”, 10126 Turin, Italy; (L.S.); (F.A.)
| | - Fiorella Altruda
- Molecular Biotechnology Centre “Guido Tarone”, 10126 Turin, Italy; (L.S.); (F.A.)
| | - Marilena Durazzo
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (A.F.); (G.S.); (S.M.); (A.G.); (M.D.)
| | - Sharmila Fagoonee
- Institute for Biostructure and Bioimaging, National Research Council (CNR), Molecular Biotechnology Centre “Guido Tarone”, 10126 Turin, Italy
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Bufkin KB, Karim ZA, Silva J. Review of the limitations of current biomarkers in acute kidney injury clinical practices. SAGE Open Med 2024; 12:20503121241228446. [PMID: 38322582 PMCID: PMC10846001 DOI: 10.1177/20503121241228446] [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: 09/26/2023] [Accepted: 01/04/2024] [Indexed: 02/08/2024] Open
Abstract
Acute kidney injury is a prevalent disease in hospitalized patients and is continuously increasing worldwide. Various efforts have been made to define and classify acute kidney injury to understand the progression of this disease. Furthermore, deviations from structure and kidney function and the current diagnostic guidelines are not adequately placed due to baseline serum creatinine values, which are rarely known and estimated based on glomerular function rate, resulting in misclassification of acute kidney injury staging. Hence, the current guidelines are still developing to improve and understand the clinical implications of risk factors and earlier predictive biomarkers of acute kidney injury. Yet, studies have indicated disadvantages and limitations with the current acute kidney injury biomarkers, including lack of sensitivity and specificity. Therefore, the present narrative review brings together the most current evidenced-based practice and literature associated with the limitations of the gold standard for acute kidney injury diagnoses, the need for novel acute kidney injury biomarkers, and the process for biomarkers to be qualified for diagnostic use under the following sections and themes. The introduction section situates the anatomy and normal and abnormal kidney functions related to acute kidney injury disorders. Guidelines in providing acute kidney injury definitions and classification are then considered, followed by a discussion of the disadvantages of standard markers used to diagnose acute kidney injury. Characteristics of an ideal acute kidney injury biomarker are discussed concerning sensitivity, specificity, and anatomic location of injury. A particular focus on the role and function of emerging biomarkers is discussed in relation to their applications and significance to the prognosis and severity of acute kidney injury. Findings show emerging markers are early indicators of acute kidney injury prediction in different clinical settings. Finally, the process required for a biomarker to be applied for diagnostic use is explained.
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Affiliation(s)
- Kendra B Bufkin
- Department of Interdisciplinary Health Science, College of Allied Health Science, Augusta University, Augusta, GA, USA
| | - Zubair A Karim
- Department of Interdisciplinary Health Science, College of Allied Health Science, Augusta University, Augusta, GA, USA
| | - Jeane Silva
- Department of Health Management, Economics and Policy, Augusta University, Augusta, GA, USA
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Kaisu L, Songlin Y, Wu S, Ying Z, Wang L, Potapov A, Yu X, Sun Y, Sun N, Zhu M. Portable and Recyclable Luminescent Lanthanide Coordination Polymer Film Sensors for Adenosine Triphosphate in Urine. ACS APPLIED MATERIALS & INTERFACES 2024; 16:5129-5137. [PMID: 38227932 DOI: 10.1021/acsami.3c16504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
Adenosine triphosphate (ATP) is a small molecule that is released to the urine from bladder urothelial cells and the bladder mucosal band of the human body. In certain cases, ATP can serve as a biomarker in bladder disease. For the practical applicability of luminescent sensors for ATP in urine, it is significant to find a new strategy for making the detection progress simple and available for in-field urine analysis. Here, a novel luminescent lanthanide coordination polymer (Tb-BPA) was designed and synthesized for quick and sensitive detection of ATP through luminescence quenching with a quenching constant of 4.90 × 103 M-1 and a detection limit of 0.55 × 10-6 M. Besides, Tb-BPA has excellent anti-interference ability and can detect ATP in simulated urine with a small relative standard deviation (<4%). Moreover, the luminescent polyacrylonitrile nanofiber films modified by Tb-BPA were prepared by electrospinning and were used for ATP visual detection. Notably, this film is easy to recover and reuse, and maintains good detection performance after at least 7 cycles.
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Affiliation(s)
- Li Kaisu
- The Key Laboratory of the Inorganic Molecule-Based Chemistry of Liaoning Province and Laboratory of Coordination, College of Science, Shenyang University of Chemical Technology, Shenyang 110142, PR China
| | - Yang Songlin
- The Key Laboratory of the Inorganic Molecule-Based Chemistry of Liaoning Province and Laboratory of Coordination, College of Science, Shenyang University of Chemical Technology, Shenyang 110142, PR China
| | - Shuangyan Wu
- The Key Laboratory of the Inorganic Molecule-Based Chemistry of Liaoning Province and Laboratory of Coordination, College of Science, Shenyang University of Chemical Technology, Shenyang 110142, PR China
| | - Zhang Ying
- The Key Laboratory of the Inorganic Molecule-Based Chemistry of Liaoning Province and Laboratory of Coordination, College of Science, Shenyang University of Chemical Technology, Shenyang 110142, PR China
| | - Lei Wang
- Center of Physical Chemistry Test, Shenyang University of Chemical Technology, Shenyang, Liaoning, College of Science, Shenyang University of Chemical Technology, Shenyang 110142, PR China
| | - Andrei Potapov
- Nikolaev Institute of Inorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, 3 Lavrentiev Avenue, Novosibirsk 630090, Russia
| | - Xiaolin Yu
- Nikolaev Institute of Inorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, 3 Lavrentiev Avenue, Novosibirsk 630090, Russia
| | - Yaguang Sun
- The Key Laboratory of the Inorganic Molecule-Based Chemistry of Liaoning Province and Laboratory of Coordination, College of Science, Shenyang University of Chemical Technology, Shenyang 110142, PR China
| | - Na Sun
- The Key Laboratory of the Inorganic Molecule-Based Chemistry of Liaoning Province and Laboratory of Coordination, College of Science, Shenyang University of Chemical Technology, Shenyang 110142, PR China
| | - MingChang Zhu
- The Key Laboratory of the Inorganic Molecule-Based Chemistry of Liaoning Province and Laboratory of Coordination, College of Science, Shenyang University of Chemical Technology, Shenyang 110142, PR China
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Tang Q, Wang S, Li H, Liu J, Hu X, Zhao D, Di M. Integrated multi-omics analyses reveal the TM4SF family genes with prognostic and therapeutic relevance in hepatocellular carcinoma. Aging (Albany NY) 2024; 16:593-616. [PMID: 38206300 PMCID: PMC10817404 DOI: 10.18632/aging.205398] [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] [Received: 08/11/2023] [Accepted: 11/16/2023] [Indexed: 01/12/2024]
Abstract
TM4SF family members (TM4SFs) have been shown to be aberrantly expressed in multiple types of cancer. However, a comprehensive investigation of the TM4SFs has yet to be performed in LIHC. The study comprehensively investigated the expression and prognostic value of TM4SFs. Then, a TM4SFs-based risk model and nomogram were constructed for prognostic prediction. Finally, functional loss of TM4SFs was performed to verify the potential role of TM4SFs in LIHC. We found that TM4SFs were significantly up-regulated in LIHC. High expression and hypomethylation of TM4SFs were associated with poor prognosis of LIHC patients. Then, a TM4SFs-based risk model was constructed that could effectively classify LIHC patients into high and low-risk groups. In addition, we constructed a prognostic nomogram that could predict the long-term survival of LIHC patients. Based on immune infiltration analysis, high-risk patients had a relatively higher immune status than low-risk patients. Moreover, the prediction module could predict patient responses to immunotherapy and chemotherapy. Finally, loss-of-function studies showed that TM4SF4 knockdown could substantially suppress the growth, migratory, and invasive abilities of LIHC cells. Targeting TM4SFs will contribute to effective immunotherapy strategies and improve the prognosis of liver cancer patients.
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Affiliation(s)
- Qiang Tang
- Department of Gastrointestinal Surgery, Shiyan Taihe Hospital, Hubei University of Medicine, Hubei Province, China
- The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China
| | - Shurui Wang
- School of Nursing, Peking Union Medical College, Beijing, China
| | - Huimin Li
- Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Junzhi Liu
- Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Xin Hu
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Dong Zhao
- Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China
| | - Maojun Di
- Department of Gastrointestinal Surgery, Shiyan Taihe Hospital, Hubei University of Medicine, Hubei Province, China
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Gupta S, Nagtode N, Chandra V, Gomase K. From Diagnosis to Treatment: Exploring the Latest Management Trends in Cervical Intraepithelial Neoplasia. Cureus 2023; 15:e50291. [PMID: 38205499 PMCID: PMC10776490 DOI: 10.7759/cureus.50291] [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: 09/11/2023] [Accepted: 12/10/2023] [Indexed: 01/12/2024] Open
Abstract
Cervical intraepithelial neoplasia (CIN) stands as a precancerous condition with the potential to progress to invasive cervical cancer. This comprehensive review explores the intricacies of CIN management, beginning with its definition, classification, and etiology. It emphasizes the significance of early detection and outlines the latest trends in diagnosis, including Pap smears, human papillomavirus (HPV) testing, and colposcopy. Grading and staging, pivotal in treatment selection, are elucidated. Current management approaches, encompassing watchful waiting, surgical interventions, emerging minimally invasive techniques, and immunotherapy, are detailed. The factors influencing treatment decisions, informed consent, and patient education are discussed. Potential complications following treatment, the importance of long-term follow-up, and the role of HPV vaccination in prevention are underscored. Finally, the review looks to the future, discussing advances in detection, novel treatments, and the promise of precision medicine. In conclusion, early detection and management remain the cornerstone of CIN care, offering hope for a future where cervical cancer is a preventable and treatable condition.
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Affiliation(s)
- Saloni Gupta
- Community Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Nikhilesh Nagtode
- Community Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Vaibhav Chandra
- Community Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Kavita Gomase
- Obstetrics and Gynecology, Smt. Radhikabai Meghe Memorial College of Nursing, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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Chung HH, Huang P, Chen CL, Lee C, Hsu CC. Next-generation pathology practices with mass spectrometry imaging. MASS SPECTROMETRY REVIEWS 2023; 42:2446-2465. [PMID: 35815718 DOI: 10.1002/mas.21795] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 04/13/2022] [Accepted: 04/22/2022] [Indexed: 06/15/2023]
Abstract
Mass spectrometry imaging (MSI) is a powerful technique that reveals the spatial distribution of various molecules in biological samples, and it is widely used in pathology-related research. In this review, we summarize common MSI techniques, including matrix-assisted laser desorption/ionization and desorption electrospray ionization MSI, and their applications in pathological research, including disease diagnosis, microbiology, and drug discovery. We also describe the improvements of MSI, focusing on the accumulation of imaging data sets, expansion of chemical coverage, and identification of biological significant molecules, that have prompted the evolution of MSI to meet the requirements of pathology practices. Overall, this review details the applications and improvements of MSI techniques, demonstrating the potential of integrating MSI techniques into next-generation pathology practices.
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Affiliation(s)
- Hsin-Hsiang Chung
- Department of Chemistry, National Taiwan University, Taipei City, Taiwan
| | - Penghsuan Huang
- Department of Chemistry, National Taiwan University, Taipei City, Taiwan
| | - Chih-Lin Chen
- Department of Chemistry, National Taiwan University, Taipei City, Taiwan
| | - Chuping Lee
- Department of Chemistry, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Cheng-Chih Hsu
- Department of Chemistry, National Taiwan University, Taipei City, Taiwan
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Lee CC, Wang TT, Lubek JE, Dyalram D. Is Preoperative Serum Albumin Predictive of Adverse Outcomes in Head and Neck Cancer Surgery? J Oral Maxillofac Surg 2023; 81:1422-1434. [PMID: 37678417 DOI: 10.1016/j.joms.2023.08.162] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/27/2023] [Accepted: 08/15/2023] [Indexed: 09/09/2023]
Abstract
BACKGROUND Patients with head and neck cancer are at increased risk of malnutrition due to tumor burden and surgical morbidity. PURPOSE The purpose of this study was to evaluate the association between preoperative serum albumin and 30-day adverse outcomes in patients undergoing head and neck cancer surgery. STUDY DESIGN, SETTING, SAMPLE This was a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program database. Patients undergoing an ablative head and neck cancer procedure were included. Patients who had an unclear tumor location based on coding or missing outcome data were excluded. PREDICTOR VARIABLE The primary predictor variable was preoperative albumin categorized as low (<3.4 g/dL), intermediate (3.4 to 3.9 g/dL), or high (>3.9 g/dL). OUTCOME VARIABLE The primary outcome variable was intensive care unit (ICU)-level complications scored using the Clavien-Dindo classification system. This is a tool used to grade surgical complications, with grade IV and V complications defined as requiring ICU-level care. COVARIATES Covariates were demographic (age, sex, body mass index), medical (smoking, functional status, weight loss), and perioperative (concurrent procedures, tumor location, reconstructive modality). ANALYSES Descriptive, bivariate, and multiple logistic regression with bootstrap resampling statistics were used to evaluate the association between albumin and adverse outcomes. A significance level of P ≤ .05 was significant. RESULTS A total of 4,491 subjects met inclusion criteria and had a documented albumin. There were 435 subjects with low albumin levels, 1,305 with intermediate levels, and 2,751 with high levels. In bivariate analysis, low albumin levels were associated with an increased risk of ICU-level complications, any complication, extended length of stay, and adverse discharge disposition (all P ≤ .001), while high levels were protective (all P ≤ .001). In bootstrapped multivariate analysis using intermediate albumin as the reference group and adjusting for demographics, tumor location, and reconstructive modality among others, low albumin levels were an independent predictor of ICU-level complications (P = .008, odds ratio, 1.64; 95% confidence interval, 1.14 to 2.40), while high levels were protective (P = .014, odds ratio, 0.689; 95% confidence interval, 0.521 to 0.923). CONCLUSIONS Preoperative serum albumin was an independent predictor of adverse outcomes following ablative head and neck cancer procedures.
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Affiliation(s)
- Cameron C Lee
- Head and Neck Oncology Fellow, Oral and Maxillofacial Surgery, University of Maryland Medical Center, Baltimore, MD.
| | - Tim T Wang
- Resident, Oral and Maxillofacial Surgery, Massachusetts General Hospital, Boston, MA
| | - Joshua E Lubek
- Head and Neck Oncology Fellowship Director and Professor, Oral and Maxillofacial Surgery, University of Maryland Medical Center, Baltimore, MD
| | - Donita Dyalram
- Residency Program Director and Associate Professor, Oral and Maxillofacial Surgery, University of Maryland Medical Center, Baltimore, MD
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Saviana M, Romano G, McElroy J, Nigita G, Distefano R, Toft R, Calore F, Le P, Morales DDV, Atmajoana S, Deppen S, Wang K, Lee LJ, Acunzo M, Nana-Sinkam P. A plasma miRNA-based classifier for small cell lung cancer diagnosis. Front Oncol 2023; 13:1255527. [PMID: 37869089 PMCID: PMC10585112 DOI: 10.3389/fonc.2023.1255527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Accepted: 09/18/2023] [Indexed: 10/24/2023] Open
Abstract
Introduction Small cell lung cancer (SCLC) is characterized by poor prognosis and challenging diagnosis. Screening in high-risk smokers results in a reduction in lung cancer mortality, however, screening efforts are primarily focused on non-small cell lung cancer (NSCLC). SCLC diagnosis and surveillance remain significant challenges. The aberrant expression of circulating microRNAs (miRNAs/miRs) is reported in many tumors and can provide insights into the pathogenesis of tumor development and progression. Here, we conducted a comprehensive assessment of circulating miRNAs in SCLC with a goal of developing a miRNA-based classifier to assist in SCLC diagnoses. Methods We profiled deregulated circulating cell-free miRNAs in the plasma of SCLC patients. We tested selected miRNAs on a training cohort and created a classifier by integrating miRNA expression and patients' clinical data. Finally, we applied the classifier on a validation dataset. Results We determined that miR-375-3p can discriminate between SCLC and NSCLC patients, and between SCLC and Squamous Cell Carcinoma patients. Moreover, we found that a model comprising miR-375-3p, miR-320b, and miR-144-3p can be integrated with race and age to distinguish metastatic SCLC from a control group. Discussion This study proposes a miRNA-based biomarker classifier for SCLC that considers clinical demographics with specific cut offs to inform SCLC diagnosis.
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Affiliation(s)
- Michela Saviana
- Department of Internal Medicine, Division of Pulmonary Diseases and Critical Care Medicine, Virginia Commonwealth University, Richmond, VA, United States
- Department of Molecular Medicine, University La Sapienza, Rome, Italy
| | - Giulia Romano
- Department of Internal Medicine, Division of Pulmonary Diseases and Critical Care Medicine, Virginia Commonwealth University, Richmond, VA, United States
| | - Joseph McElroy
- Center for Biostatistics, The Ohio State University, Columbus, OH, United States
| | - Giovanni Nigita
- Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, United States
| | - Rosario Distefano
- Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, United States
| | - Robin Toft
- Department of Internal Medicine, Division of Pulmonary Diseases and Critical Care Medicine, Virginia Commonwealth University, Richmond, VA, United States
| | - Federica Calore
- Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, United States
| | - Patricia Le
- Department of Internal Medicine, Division of Pulmonary Diseases and Critical Care Medicine, Virginia Commonwealth University, Richmond, VA, United States
| | - Daniel Del Valle Morales
- Department of Internal Medicine, Division of Pulmonary Diseases and Critical Care Medicine, Virginia Commonwealth University, Richmond, VA, United States
| | - Sarah Atmajoana
- Vanderbilt University Medical Center and Tennessee Valley Healthcare System, Nashville, TN, United States
| | - Stephen Deppen
- Vanderbilt University Medical Center and Tennessee Valley Healthcare System, Nashville, TN, United States
| | - Kai Wang
- Institute for System Biology, Seattle, WA, United States
| | - L. James Lee
- Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, United States
| | - Mario Acunzo
- Department of Internal Medicine, Division of Pulmonary Diseases and Critical Care Medicine, Virginia Commonwealth University, Richmond, VA, United States
| | - Patrick Nana-Sinkam
- Department of Internal Medicine, Division of Pulmonary Diseases and Critical Care Medicine, Virginia Commonwealth University, Richmond, VA, United States
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Cai Y, Liu P, Xu Y, Xia Y, Peng X, Zhao H, Chen Q. Biomarkers of obesity-mediated insulin resistance: focus on microRNAs. Diabetol Metab Syndr 2023; 15:167. [PMID: 37537674 PMCID: PMC10401761 DOI: 10.1186/s13098-023-01137-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 07/09/2023] [Indexed: 08/05/2023] Open
Abstract
Obesity and metabolic syndromes are becoming increasingly prevalent worldwide. Insulin resistance (IR) is a common complication of obesity. However, IR occurrence varies across individuals with obesity and may involve epigenetic factors. To rationalize the allocation of healthcare resources, biomarkers for the early risk stratification of individuals with obesity should be identified. MicroRNAs (miRNAs) are closely associated with metabolic diseases and involved in epigenetic regulation. In this review, we have summarized the changes in miRNA expression in the peripheral circulation and tissues of patients and animals with obesity-associated IR over the last 5 years and identified several candidate biomarkers that predict obesity-related IR. There are areas for improvement in existing studies. First, more than the predictive validity of a single biomarker is required, and a biomarker panel needs to be formed. Second, miRNAs are often studied in isolation and do not form a network of signaling pathways. We believe that early biomarkers can help clinicians accurately predict individuals prone to obesity-related IR at an early stage. Epigenetic regulation may be one of the underlying causes of different clinical outcomes in individuals with obesity. Future studies should focus on objectively reflecting the differences in miRNA profile expression in individuals with obesity-related IR, which may help identify more reliable biomarkers. Understanding the metabolic pathways of these miRNAs can help design new metabolic risk prevention and management strategies, and support the development of drugs to treat obesity and metabolic disorders.
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Affiliation(s)
- Yichen Cai
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan, China
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Pan Liu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan, China
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yumei Xu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan, China
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yuguo Xia
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan, China
| | - Xiaowan Peng
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan, China
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Haiyan Zhao
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan, China
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qiu Chen
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan, China.
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Kan CM, Pei XM, Yeung MHY, Jin N, Ng SSM, Tsang HF, Cho WCS, Yim AKY, Yu ACS, Wong SCC. Exploring the Role of Circulating Cell-Free RNA in the Development of Colorectal Cancer. Int J Mol Sci 2023; 24:11026. [PMID: 37446204 PMCID: PMC10341751 DOI: 10.3390/ijms241311026] [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: 05/21/2023] [Revised: 06/25/2023] [Accepted: 07/02/2023] [Indexed: 07/15/2023] Open
Abstract
Circulating tumor RNA (ctRNA) has recently emerged as a novel and attractive liquid biomarker. CtRNA is capable of providing important information about the expression of a variety of target genes noninvasively, without the need for biopsies, through the use of circulating RNA sequencing. The overexpression of cancer-specific transcripts increases the tumor-derived RNA signal, which overcomes limitations due to low quantities of circulating tumor DNA (ctDNA). The purpose of this work is to present an up-to-date review of current knowledge regarding ctRNAs and their status as biomarkers to address the diagnosis, prognosis, prediction, and drug resistance of colorectal cancer. The final section of the article discusses the practical aspects involved in analyzing plasma ctRNA, including storage and isolation, detection technologies, and their limitations in clinical applications.
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Affiliation(s)
- Chau-Ming Kan
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, China; (C.-M.K.); (H.F.T.)
| | - Xiao Meng Pei
- Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hong Kong SAR, China; (X.M.P.); (M.H.Y.Y.)
| | - Martin Ho Yin Yeung
- Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hong Kong SAR, China; (X.M.P.); (M.H.Y.Y.)
| | - Nana Jin
- Codex Genetics Limited, Shatin, Hong Kong SAR, China; (N.J.); (A.K.-Y.Y.); (A.C.-S.Y.)
| | - Simon Siu Man Ng
- Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China;
| | - Hin Fung Tsang
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, China; (C.-M.K.); (H.F.T.)
| | - William Chi Shing Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong SAR, China;
| | - Aldrin Kay-Yuen Yim
- Codex Genetics Limited, Shatin, Hong Kong SAR, China; (N.J.); (A.K.-Y.Y.); (A.C.-S.Y.)
| | - Allen Chi-Shing Yu
- Codex Genetics Limited, Shatin, Hong Kong SAR, China; (N.J.); (A.K.-Y.Y.); (A.C.-S.Y.)
| | - Sze Chuen Cesar Wong
- Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hong Kong SAR, China; (X.M.P.); (M.H.Y.Y.)
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Suddull HJ, Rosa-Fernandes L, Lee A. How can proteomics help solve the lack of biomarkers to aid in the early diagnosis of motor neuron disease (MND)? Expert Rev Proteomics 2023; 20:121-123. [PMID: 37480213 DOI: 10.1080/14789450.2023.2240513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 06/29/2023] [Indexed: 07/23/2023]
Affiliation(s)
- Hannah Jane Suddull
- Macquarie University Centre for Motor Neuron Disease Research, Sydney, Australia
| | - Livia Rosa-Fernandes
- Macquarie University Centre for Motor Neuron Disease Research, Sydney, Australia
| | - Albert Lee
- Macquarie University Centre for Motor Neuron Disease Research, Sydney, Australia
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