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Teryaeva N, Kvan O, Strunina Y, Kulikov A. Laboratory Markers of Impaired Erythropoiesis in Early Diagnosis of Perioperative Anemias. Sovrem Tekhnologii Med 2025; 17:48-53. [PMID: 40416501 PMCID: PMC12096359 DOI: 10.17691/stm2025.17.2.05] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Indexed: 05/27/2025] Open
Abstract
The aim of the study was to assess the diagnostic value of laboratory indicators of hemoglobin content in reticulocytes for the early detection of predisposition for perioperative anemia in patients with total hemoglobin within the reference range. Materials and Methods Observational retrospective single-center continuous cross-sectional study has been carried out to determine the need for transfusion of erythrocyte-containing components (ECC) depending on the values of reticulocyte hemoglobin (Ret-He) and delta-hemoglobin (Delta-He) in patients with unchanged (within the reference range) values of the total hemoglobin. The groups of comparison were formed using the diagnostic Hema-Plot algorithm, under which Ret-He and Delta-He values deviate from the reference range towards greater or smaller magnitudes in various types of anemia. Results Deviations from the reference intervals of Ret-He and Delta-He values were observed in 26% of patients not formally meeting the WHO criteria for anemia on admission. Indications for ECC transfusion therapy were more likely to occur in patients who had changes in Ret-He and Delta-He corresponding to the signs of anemias of different genesis according to the Hema-Plot algorithm. Conclusion The Ret-He and Delta-He values in patients with unchanged hemoglobin allow for making a decision on the need for ECC transfusion therapy in the postoperative period.The differences between the groups formed on the basis of Ret-He and Delta-He deviations from the reference values are in line with the diagnostic signs of anemias of various origins. They also allow one to discuss the variants of impaired erythropoiesis at the very early stages of the disorder and the risk of anemia development in patients with formally unchanged total hemoglobin levels.
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Affiliation(s)
- N.B. Teryaeva
- Clinical Laboratory Diagnostician; N.N. Burdenko National Medical Research Center for Neurosurgery, Ministry of Health of the Russian Federation, 16, 4 Tverskaya-Yamskaya St., Moscow, 125047, Russia
| | - O.K. Kvan
- Head of the Department of Clinical and Industrial Transfusiology; N.N. Burdenko National Medical Research Center for Neurosurgery, Ministry of Health of the Russian Federation, 16, 4 Tverskaya-Yamskaya St., Moscow, 125047, Russia
| | - Yu.V. Strunina
- Leading Engineer; N.N. Burdenko National Medical Research Center for Neurosurgery, Ministry of Health of the Russian Federation, 16, 4 Tverskaya-Yamskaya St., Moscow, 125047, Russia
| | - A.S. Kulikov
- Head of the Anesthesiology-Resuscitation Department; N.N. Burdenko National Medical Research Center for Neurosurgery, Ministry of Health of the Russian Federation, 16, 4 Tverskaya-Yamskaya St., Moscow, 125047, Russia
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Battaglini M, Marino A, Montorsi M, Carmignani A, Ceccarelli MC, Ciofani G. Nanomaterials as Microglia Modulators in the Treatment of Central Nervous System Disorders. Adv Healthc Mater 2024; 13:e2304180. [PMID: 38112345 DOI: 10.1002/adhm.202304180] [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: 12/11/2023] [Indexed: 12/21/2023]
Abstract
Microglia play a pivotal role in the central nervous system (CNS) homeostasis, acting as housekeepers and defenders of the surrounding environment. These cells can elicit their functions by shifting into two main phenotypes: pro-inflammatory classical phenotype, M1, and anti-inflammatory alternative phenotype, M2. Despite their pivotal role in CNS homeostasis, microglia phenotypes can influence the development and progression of several CNS disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, ischemic stroke, traumatic brain injuries, and even brain cancer. It is thus clear that the possibility of modulating microglia activation has gained attention as a therapeutic tool against many CNS pathologies. Nanomaterials are an unprecedented tool for manipulating microglia responses, in particular, to specifically target microglia and elicit an in situ immunomodulation activity. This review focuses the discussion on two main aspects: analyzing the possibility of using nanomaterials to stimulate a pro-inflammatory response of microglia against brain cancer and introducing nanostructures able to foster an anti-inflammatory response for treating neurodegenerative disorders. The final aim is to stimulate the analysis of the development of new microglia nano-immunomodulators, paving the way for innovative and effective therapeutic approaches for the treatment of CNS disorders.
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Affiliation(s)
- Matteo Battaglini
- Istituto Italiano di Tecnologia, Smart Bio-Interfaces, Viale Rinaldo Piaggio 34, Pontedera, 56025, Italy
| | - Attilio Marino
- Istituto Italiano di Tecnologia, Smart Bio-Interfaces, Viale Rinaldo Piaggio 34, Pontedera, 56025, Italy
| | - Margherita Montorsi
- Istituto Italiano di Tecnologia, Smart Bio-Interfaces, Viale Rinaldo Piaggio 34, Pontedera, 56025, Italy
- Scuola Superiore Sant'Anna, The BioRobotics Institute, Viale Rinaldo Piaggio 34, Pontedera, 56025, Italy
| | - Alessio Carmignani
- Istituto Italiano di Tecnologia, Smart Bio-Interfaces, Viale Rinaldo Piaggio 34, Pontedera, 56025, Italy
- Scuola Superiore Sant'Anna, The BioRobotics Institute, Viale Rinaldo Piaggio 34, Pontedera, 56025, Italy
| | - Maria Cristina Ceccarelli
- Istituto Italiano di Tecnologia, Smart Bio-Interfaces, Viale Rinaldo Piaggio 34, Pontedera, 56025, Italy
- Scuola Superiore Sant'Anna, The BioRobotics Institute, Viale Rinaldo Piaggio 34, Pontedera, 56025, Italy
| | - Gianni Ciofani
- Istituto Italiano di Tecnologia, Smart Bio-Interfaces, Viale Rinaldo Piaggio 34, Pontedera, 56025, Italy
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Singh S, Joshi V, Upadhyay A. Amyloids and brain cancer: molecular linkages and crossovers. Biosci Rep 2023; 43:BSR20230489. [PMID: 37335084 PMCID: PMC10548166 DOI: 10.1042/bsr20230489] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 05/31/2023] [Accepted: 06/13/2023] [Indexed: 06/21/2023] Open
Abstract
Amyloids are high-order proteinaceous formations deposited in both intra- and extracellular spaces. These aggregates have tendencies to deregulate cellular physiology in multiple ways; for example, altered metabolism, mitochondrial dysfunctions, immune modulation, etc. When amyloids are formed in brain tissues, the endpoint often is death of neurons. However, interesting but least understood is a close connection of amyloids with another set of conditions in which brain cells proliferate at an extraordinary rate and form tumor inside brain. Glioblastoma is one such condition. Increasing number of evidence indicate a possible link between amyloid formation and depositions in brain tumors. Several proteins associated with cell cycle regulation and apoptotic pathways themselves have shown to possess high tendencies to form amyloids. Tumor suppressor protein p53 is one prominent example that mutate, oligomerize and form amyloids leading to loss- or gain-of-functions and cause increased cell proliferation and malignancies. In this review article, we present available examples, genetic links and common pathways that indicate that possibly the two distantly placed pathways: amyloid formation and developing cancers in the brain have similarities and are mechanistically intertwined together.
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Affiliation(s)
- Shalini Singh
- Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, Jheepasani, Jodhpur, Rajasthan 342001, India
- Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, U.S.A
| | - Vibhuti Joshi
- Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, Jheepasani, Jodhpur, Rajasthan 342001, India
- Department of Biotechnology, School of Engineering and Applied Sciences, Bennett University, Greater Noida, Uttar Pradesh 201310, India
| | - Arun Upadhyay
- Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, Jheepasani, Jodhpur, Rajasthan 342001, India
- Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, U.S.A
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Mouliou DS. C-Reactive Protein: Pathophysiology, Diagnosis, False Test Results and a Novel Diagnostic Algorithm for Clinicians. Diseases 2023; 11:132. [PMID: 37873776 PMCID: PMC10594506 DOI: 10.3390/diseases11040132] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 09/15/2023] [Accepted: 09/19/2023] [Indexed: 10/25/2023] Open
Abstract
The current literature provides a body of evidence on C-Reactive Protein (CRP) and its potential role in inflammation. However, most pieces of evidence are sparse and controversial. This critical state-of-the-art monography provides all the crucial data on the potential biochemical properties of the protein, along with further evidence on its potential pathobiology, both for its pentameric and monomeric forms, including information for its ligands as well as the possible function of autoantibodies against the protein. Furthermore, the current evidence on its potential utility as a biomarker of various diseases is presented, of all cardiovascular, respiratory, hepatobiliary, gastrointestinal, pancreatic, renal, gynecological, andrological, dental, oral, otorhinolaryngological, ophthalmological, dermatological, musculoskeletal, neurological, mental, splenic, thyroid conditions, as well as infections, autoimmune-supposed conditions and neoplasms, including other possible factors that have been linked with elevated concentrations of that protein. Moreover, data on molecular diagnostics on CRP are discussed, and possible etiologies of false test results are highlighted. Additionally, this review evaluates all current pieces of evidence on CRP and systemic inflammation, and highlights future goals. Finally, a novel diagnostic algorithm to carefully assess the CRP level for a precise diagnosis of a medical condition is illustrated.
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Eyraud R, Ayache S, Tsvetkov PO, Kalidindi SS, Baksheeva VE, Boissonneau S, Jiguet-Jiglaire C, Appay R, Nanni-Metellus I, Chinot O, Devred F, Tabouret E. Plasma nanoDSF Denaturation Profile at Baseline Is Predictive of Glioblastoma EGFR Status. Cancers (Basel) 2023; 15:cancers15030760. [PMID: 36765718 PMCID: PMC9913157 DOI: 10.3390/cancers15030760] [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: 10/09/2022] [Revised: 01/05/2023] [Accepted: 01/18/2023] [Indexed: 01/28/2023] Open
Abstract
Glioblastoma (GBM) is the most frequent and aggressive primary brain tumor in adults. Recently, we demonstrated that plasma denaturation profiles of glioblastoma patients obtained using Differential Scanning Fluorimetry can be automatically distinguished from healthy controls with the help of Artificial Intelligence (AI). Here, we used a set of machine-learning algorithms to automatically classify plasma denaturation profiles of glioblastoma patients according to their EGFR status. We found that Adaboost AI is able to discriminate EGFR alterations in GBM with an 81.5% accuracy. Our study shows that the use of these plasma denaturation profiles could answer the unmet neuro-oncology need for diagnostic predictive biomarker in combination with brain MRI and clinical data, in order to allow for a rapid orientation of patients for a definitive pathological diagnosis and then treatment. We complete this study by showing that discriminating another mutation, MGMT, seems harder, and that post-surgery monitoring using our approach is not conclusive in the 48 h that follow the surgery.
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Affiliation(s)
- Rémi Eyraud
- Laboratoire Hubert Curien UMR 5516, UJM-Saint-Etienne, University Lyon, CNRS, 42000 Saint Etienne, France
| | | | - Philipp O. Tsvetkov
- Inst Neurophysiopathol, INP, Faculté des Sciences Médicales et Paramédicales, Aix Marseille Univ, CNRS, 13005 Marseille, France
- Plateforme Interactome Timone, PINT, Faculté des Sciences Médicales et Paramédicales, Aix Marseille Univ, 13005 Marseille, France
| | - Shanmugha Sri Kalidindi
- Laboratoire Hubert Curien UMR 5516, UJM-Saint-Etienne, University Lyon, CNRS, 42000 Saint Etienne, France
| | - Viktoriia E. Baksheeva
- Inst Neurophysiopathol, INP, Faculté des Sciences Médicales et Paramédicales, Aix Marseille Univ, CNRS, 13005 Marseille, France
| | | | - Carine Jiguet-Jiglaire
- Inst Neurophysiopathol, INP, Faculté des Sciences Médicales et Paramédicales, Aix Marseille Univ, CNRS, 13005 Marseille, France
- Department of Anatomopathology, Timone Hospital, APHM, 13005 Marseille, France
| | - Romain Appay
- Inst Neurophysiopathol, INP, Faculté des Sciences Médicales et Paramédicales, Aix Marseille Univ, CNRS, 13005 Marseille, France
- Department of Anatomopathology, Timone Hospital, APHM, 13005 Marseille, France
| | | | - Olivier Chinot
- Inst Neurophysiopathol, INP, Faculté des Sciences Médicales et Paramédicales, Aix Marseille Univ, CNRS, 13005 Marseille, France
- Service de Neurooncologie, CHU Timone, APHM, 13005 Marseille, France
| | - François Devred
- Inst Neurophysiopathol, INP, Faculté des Sciences Médicales et Paramédicales, Aix Marseille Univ, CNRS, 13005 Marseille, France
- Plateforme Interactome Timone, PINT, Faculté des Sciences Médicales et Paramédicales, Aix Marseille Univ, 13005 Marseille, France
- Correspondence: (F.D.); (E.T.)
| | - Emeline Tabouret
- Inst Neurophysiopathol, INP, Faculté des Sciences Médicales et Paramédicales, Aix Marseille Univ, CNRS, 13005 Marseille, France
- Service de Neurooncologie, CHU Timone, APHM, 13005 Marseille, France
- Correspondence: (F.D.); (E.T.)
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Ten Cate C, Huijs SMH, Willemsen ACH, Pasmans RCOS, Eekers DBP, Zegers CML, Ackermans L, Beckervordersandforth J, van Raak EPM, Anten MHME, Hoeben A, Postma AA, Broen MPG. Correlation of reduced temporal muscle thickness and systemic muscle loss in newly diagnosed glioblastoma patients. J Neurooncol 2022; 160:611-618. [PMID: 36394717 PMCID: PMC9758090 DOI: 10.1007/s11060-022-04180-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 10/21/2022] [Indexed: 11/18/2022]
Abstract
PURPOSE Reduced temporal muscle thickness (TMT) has recently been postulated as a prognostic imaging marker and an objective tool to assess patients frailty in glioblastoma. Our aim is to investigate the correlation of TMT and systemic muscle loss to confirm that TMT is an adequate surrogate marker of sarcopenia in newly diagnosed glioblastoma patients. METHODS TMT was assessed on preoperative MR-images and skeletal muscle area (SMA) was assessed at the third lumbar vertebra on preoperative abdominal CT-scans. Previous published TMT sex-specific cut-off values were used to classify patients as 'patient at risk of sarcopenia' or 'patient with normal muscle status'. Correlation between TMT and SMA was assessed using Spearman's rank correlation coefficient. RESULTS Sixteen percent of the 245 included patients were identified as at risk of sarcopenia. The mean SMA of glioblastoma patients at risk of sarcopenia (124.3 cm2, SD 30.8 cm2) was significantly lower than the mean SMA of patients with normal muscle status (146.3 cm2, SD 31.1 cm2, P < .001). We found a moderate association between TMT and SMA in the patients with normal muscle status (Spearman's rho 0.521, P < .001), and a strong association in the patients at risk of sarcopenia (Spearman's rho 0.678, P < .001). CONCLUSION Our results confirm the use of TMT as a surrogate marker of total body skeletal muscle mass in glioblastoma, especially in frail patients at risk of sarcopenia. TMT can be used to identify patients with muscle loss early in the disease process, which enables the implementation of adequate intervention strategies.
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Affiliation(s)
- Cecil Ten Cate
- Master of Science in Medicine and Clinical Research, Maastricht University, Maastricht, The Netherlands
| | - Sandra M H Huijs
- Department of Neurology Zuyderland Medical Center, Heerlen, The Netherlands
| | - Anna C H Willemsen
- GROW-School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands
- Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands
- Division of Medical Oncology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
| | | | - Daniëlle B P Eekers
- Department of Radiation Oncology (Maastro), GROW School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Catharina M L Zegers
- Department of Radiation Oncology (Maastro), GROW School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Linda Ackermans
- Department of Neurosurgery, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Jan Beckervordersandforth
- GROW-School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands
- Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Elisabeth P M van Raak
- Department of Neurology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands
| | - Monique H M E Anten
- GROW-School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands
- Department of Neurology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands
| | - Ann Hoeben
- GROW-School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands
- Division of Medical Oncology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Alida A Postma
- Department of Radiology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Martinus P G Broen
- GROW-School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands.
- Department of Neurology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands.
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Is Caperatic Acid the Only Compound Responsible for Activity of Lichen Platismatia glauca within the Nervous System? Antioxidants (Basel) 2022; 11:antiox11102069. [PMID: 36290793 PMCID: PMC9598164 DOI: 10.3390/antiox11102069] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 10/13/2022] [Accepted: 10/14/2022] [Indexed: 11/26/2022] Open
Abstract
Lichens are a source of various biologically active compounds. However, the knowledge about them is still scarce, and their use in medicine is limited. This study aimed to investigate the therapeutic potential of the lichen Platismatia glauca and its major metabolite caperatic acid in regard to their potential application in the treatment of central nervous system diseases, especially neurodegenerative diseases and brain tumours, such as glioblastoma. First, we performed the phytochemical analysis of the tested P. glauca extracts based on FT-IR derivative spectroscopic and gas chromatographic results. Next the antioxidant properties were determined, and moderate anti-radical activity, strong chelating properties of Cu2+ and Fe2+ ions, and a mild effect on the antioxidant enzymes of the tested extracts and caperatic acid were proved. Subsequently, the influence of the tested extracts and caperatic acid on cholinergic transmission was determined by in vitro and in silico studies confirming that inhibitory effect on butyrylcholinesterase is stronger than against acetylcholinesterase. We also confirmed the anti-inflammatory properties of P. glauca extracts and caperatic acid using a COX-2 and hyaluronidase inhibition models. Moreover, our studies show the cytotoxic and pro-apoptotic activity of the P. glauca extracts against T98G and U-138 MG glioblastoma multiforme cell lines. In conclusion, it is possible to assume that P. glauca extracts and especially caperatic acid can be regarded as the source of the valuable substances to finding new therapies of central nervous system diseases.
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Mamun AA, Uddin MS, Perveen A, Jha NK, Alghamdi BS, Jeandet P, Zhang HJ, Ashraf GM. Inflammation-targeted nanomedicine against brain cancer: From design strategies to future developments. Semin Cancer Biol 2022; 86:101-116. [PMID: 36084815 DOI: 10.1016/j.semcancer.2022.08.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 08/08/2022] [Accepted: 08/21/2022] [Indexed: 02/07/2023]
Abstract
Brain cancer is an aggressive type of cancer with poor prognosis. While the immune system protects against cancer in the early stages, the tumor exploits the healing arm of inflammatory reactions to accelerate its growth and spread. Various immune cells penetrate the developing tumor region, establishing a pro-inflammatory tumor milieu. Additionally, tumor cells may release chemokines and cytokines to attract immune cells and promote cancer growth. Inflammation and its associated mechanisms in the progression of cancer have been extensively studied in the majority of solid tumors, especially brain tumors. However, treatment of the malignant brain cancer is hindered by several obstacles, such as the blood-brain barrier, transportation inside the brain interstitium, inflammatory mediators that promote tumor growth and invasiveness, complications in administering therapies to tumor cells specifically, the highly invasive nature of gliomas, and the resistance to drugs. To resolve these obstacles, nanomedicine could be a potential strategy that has facilitated advancements in diagnosing and treating brain cancer. Due to the numerous benefits provided by their small size and other features, nanoparticles have been a prominent focus of research in the drug-delivery field. The purpose of this article is to discuss the role of inflammatory mediators and signaling pathways in brain cancer as well as the recent advances in understanding the nano-carrier approaches for enhancing drug delivery to the brain in the treatment of brain cancer.
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Affiliation(s)
- Abdullah Al Mamun
- Teaching and Research Division, School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Kowloon, Hong Kong Special Administrative Region of China
| | - Md Sahab Uddin
- Department of Pharmacy, Southeast University, Dhaka, Bangladesh; Pharmakon Neuroscience Research Network, Dhaka, Bangladesh
| | - Asma Perveen
- Glocal School of Life Sciences, Glocal University, Mirzapur Pole, Saharanpur, Uttar Pradesh, India
| | - Niraj Kumar Jha
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, Uttar Pradesh 201310, India; Department of Biotechnology, School of Applied & Life Sciences, Uttaranchal University, Dehradun 248007, India
| | - Badrah S Alghamdi
- Department of Physiology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; Pre-Clinical Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; The Neuroscience Research Unit, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Philippe Jeandet
- University of Reims Champagne-Ardenne, Research Unit, Induced Resistance and Plant Bioprotection, EA 4707, SFR Condorcet FR CNRS 3417, Faculty of Sciences, PO Box 1039, 51687 Reims Cedex 2, France
| | - Hong-Jie Zhang
- Teaching and Research Division, School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Kowloon, Hong Kong Special Administrative Region of China
| | - Ghulam Md Ashraf
- Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, University City, Sharjah 27272, United Arab Emirates.
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Multiple Faces of the Glioblastoma Microenvironment. Int J Mol Sci 2022; 23:ijms23020595. [PMID: 35054779 PMCID: PMC8775531 DOI: 10.3390/ijms23020595] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 12/31/2021] [Accepted: 01/03/2022] [Indexed: 12/23/2022] Open
Abstract
The tumor microenvironment is a highly dynamic accumulation of resident and infiltrating tumor cells, responsible for growth and invasion. The authors focused on the leading-edge concepts regarding the glioblastoma microenvironment. Due to the fact that the modern trend in the research and treatment of glioblastoma is represented by multiple approaches that target not only the primary tumor but also the neighboring tissue, the study of the microenvironment in the peritumoral tissue is an appealing direction for current and future therapies.
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10
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Gandhi P, Shrivastava R, Garg N, Sorte SK. Novel molecular panel for evaluating systemic inflammation and survival in therapy naïve glioma patients. World J Clin Oncol 2021; 12:947-959. [PMID: 34733616 PMCID: PMC8546655 DOI: 10.5306/wjco.v12.i10.947] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 06/21/2021] [Accepted: 08/20/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Inflammation is crucial to tumor progression. A traumatic event at a specific site in the brain activates the signaling molecules, which triggers inflammation as the initial response within the tumor and its surroundings. The educated immune cells and secreted proteins then initiate the inflammatory cascade leading to persistent chronic inflammation. Therefore, estimation of the circulating inflammatory indicators kynurenine (KYN), interleukin-6 (IL-6), tissue-inhibitor of matrix-metalloproteinase-1 and human telomerase reverse transcriptase (hTERT) along with neutrophil-lymphocyte ratio (NLR) has prognostic value. AIM To assess the utility of chosen inflammatory marker panel in estimating systemic inflammation. METHODS The chosen markers were quantitatively evaluated in 90 naive, molecularly sub-typed plasma samples of glioma. A correlation between the markers and confounders was assessed to establish their prognostication power. Follow-up on the levels of the indicators was done 3-mo post-surgery. To establish the validity of circulating KYN, it was also screened qualitatively by dot-immune-assay and by immunofluorescence-immunohistochemistry in tumor tissues. RESULTS Median values of circulating KYN, IL-6, hTERT, tissue-inhibitor of matrix-metalloproteinase-1 and NLR in isocitrate-dehydrogenase-mutant/wildtype and within the astrocytic sub-groups were estimated, which differed from controls, reaching statistical significance (P < 0.0001). All markers negatively correlated with mortality (P < 0.0001). Applying combination-statistics, the panel of KYN, IL-6, hTERT and NLR achieved higher sensitivity and specificity (> 90%) than stand-alone markers, to define survival. The inflammatory panel could discriminate between WHO grades, and isocitrate-dehydrogenase-mutant/wildtype and define differential survival between astrocytic isocitrate-dehydrogenase-mutant/wildtype. Therefore, its assessment for precise disease prognosis is indicated. Association of KYN with NLR, IL-6 and hTERT was significant. Cox-regression described KYN, IL-6, NLR, and hTERT as good prognostic markers, independent of confounders. Multivariate linear-regression analysis confirmed the association of KYN and hTERT with inflammation marker IL-6.There was a concomitant significant decrease in their levels in a 3-mo follow-up. CONCLUSION The first evidence-based study of circulating-KYN in molecularly defined gliomas, wherein the tissue expression was found to be concomitant with plasma levels. A non-invasive model for assessing indicators of chronic systemic inflammation is proposed.
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Affiliation(s)
- Puneet Gandhi
- Department of Research, Bhopal Memorial Hospital and Research Centre, Bhopal 462038, Madhya Pradesh, India
| | - Richa Shrivastava
- Department of Research, Bhopal Memorial Hospital and Research Centre, Bhopal 462038, Madhya Pradesh, India
| | - Nitin Garg
- Department of Neurosurgery, Bhopal Memorial Hospital and Research Centre, Bhopal 462038, Madhya Pradesh, India
| | - Sandeep K Sorte
- Department of Neurosurgery, Bhopal Memorial Hospital and Research Centre, Bhopal 462038, Madhya Pradesh, India
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Zandstra J, Jongerius I, Kuijpers TW. Future Biomarkers for Infection and Inflammation in Febrile Children. Front Immunol 2021; 12:631308. [PMID: 34079538 PMCID: PMC8165271 DOI: 10.3389/fimmu.2021.631308] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 04/12/2021] [Indexed: 01/08/2023] Open
Abstract
Febrile patients, suffering from an infection, inflammatory disease or autoimmunity may present with similar or overlapping clinical symptoms, which makes early diagnosis difficult. Therefore, biomarkers are needed to help physicians form a correct diagnosis and initiate the right treatment to improve patient outcomes following first presentation or admittance to hospital. Here, we review the landscape of novel biomarkers and approaches of biomarker discovery. We first discuss the use of current plasma parameters and whole blood biomarkers, including results obtained by RNA profiling and mass spectrometry, to discriminate between bacterial and viral infections. Next we expand upon the use of biomarkers to distinguish between infectious and non-infectious disease. Finally, we discuss the strengths as well as the potential pitfalls of current developments. We conclude that the use of combination tests, using either protein markers or transcriptomic analysis, have advanced considerably and should be further explored to improve current diagnostics regarding febrile infections and inflammation. If proven effective when combined, these biomarker signatures will greatly accelerate early and tailored treatment decisions.
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Affiliation(s)
- Judith Zandstra
- Division Research and Landsteiner Laboratory, Department of Immunopathology, Sanquin Blood Supply, Amsterdam University Medical Center (UMC), Amsterdam, Netherlands
- Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, Netherlands
| | - Ilse Jongerius
- Division Research and Landsteiner Laboratory, Department of Immunopathology, Sanquin Blood Supply, Amsterdam University Medical Center (UMC), Amsterdam, Netherlands
- Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, Netherlands
| | - Taco W. Kuijpers
- Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, Netherlands
- Division Research and Landsteiner Laboratory, Department of Blood Cell Research, Sanquin Blood Supply, Amsterdam UMC, Amsterdam, Netherlands
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