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Li T, Li YP. Innovative diagnostic tool aids screening for minimal hepatic encephalopathy in non-alcoholic cirrhosis patients. World J Hepatol 2025; 17:101420. [PMID: 39871897 PMCID: PMC11736476 DOI: 10.4254/wjh.v17.i1.101420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Revised: 11/30/2024] [Accepted: 12/19/2024] [Indexed: 01/06/2025] Open
Abstract
In this editorial we comment on the article by Jiang et al. We focus on the EncephalApp Stroop test which is an innovative, smartphone-based tool specifically designed for screening minimal hepatic encephalopathy (MHE) in cirrhosis patients. Traditional MHE screening methods, while highly sensitive and specific, are often complex, time-consuming, and require controlled environmental conditions, limiting their widespread clinical use. The EncephalApp Stroop test simplifies the screening process, enhances diagnostic efficiency, and is applicable across diverse cultural contexts. However, the combination of additional biomarkers could further improve diagnostic accuracy. Despite its promising potential, more multicenter clinical studies are required to validate its effectiveness and applicability on a global scale.
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Affiliation(s)
- Ting Li
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University (Xibei Hospital), Xi'an 710004, Shaanxi Province, China
| | - Ya-Ping Li
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University (Xibei Hospital), Xi'an 710004, Shaanxi Province, China.
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Karmelić I, Rubić I, Starčević K, Ozretić D, Poljaković Z, Sajko MJ, Kalousek V, Kalanj R, Rešetar Maslov D, Kuleš J, Roje Bedeković M, Sajko T, Rotim K, Mrljak V, Fabris D. Comparative Targeted Metabolomics of Ischemic Stroke: Thrombi and Serum Profiling for the Identification of Stroke-Related Metabolites. Biomedicines 2024; 12:1731. [PMID: 39200198 PMCID: PMC11351249 DOI: 10.3390/biomedicines12081731] [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: 06/27/2024] [Revised: 07/23/2024] [Accepted: 07/31/2024] [Indexed: 09/02/2024] Open
Abstract
Ischemic stroke is one of the leading causes of death and permanent disability in the world. Rapid diagnosis and intervention are crucial for reducing its consequences on individuals and societies. Therefore, identifying reliable biomarkers for early detection, prognostics, and therapy can facilitate the early prediction and prevention of stroke. Metabolomics has been shown as a promising tool for biomarker discovery since many post-ischemic metabolites can be found in the plasma or serum of the patient. In this research, we performed a comparative targeted metabolomic analysis of stroke thrombi, stroke patient serums, and healthy control serums in order to determine the alteration in the patients' metabolomes, which might serve as biomarkers for early prediction or stroke prevention. The most statistically altered metabolites characterized in the patient serums compared with the control serums were glutamate and serotonin, followed by phospholipids and triacylglycerols. In stroke thrombi compared with the patients' serums, the most significantly altered metabolites were classified as lipids, with choline-containing phospholipids and sphingomyelins having the highest discriminatory score. The results of this preliminary study could help in understanding the roles of different metabolic changes that occur during thrombosis and cerebral ischemia and possibly suggest new metabolic biomarkers for ischemic stroke.
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Affiliation(s)
- Ivana Karmelić
- Department of Medical Chemistry, Biochemistry and Clinical Chemistry, School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia
| | - Ivana Rubić
- Laboratory of Proteomics, Clinic for Internal Diseases, Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55, 10000 Zagreb, Croatia
| | - Katarina Starčević
- Department of Neurology, University Hospital Centre “Zagreb”, Kišpatićeva 12, 10000 Zagreb, Croatia
| | - David Ozretić
- Department of Diagnostic and Interventional Neuroradiology, University Hospital Centre “Zagreb”, Kišpatićeva 12, 10000 Zagreb, Croatia
| | - Zdravka Poljaković
- Department of Neurology, University Hospital Centre “Zagreb”, Kišpatićeva 12, 10000 Zagreb, Croatia
| | - Mia Jurilj Sajko
- Department of Neurosurgery, University Hospital Centre “Sestre Milosrdnice”, Vinogradska cesta 29, 10000 Zagreb, Croatia
| | - Vladimir Kalousek
- Department of Radiology, University Hospital Centre “Sestre Milosrdnice”, Vinogradska cesta 29, 10000 Zagreb, Croatia
| | - Rafaela Kalanj
- Department of Neurology, University Hospital Centre “Sestre Milosrdnice”, Vinogradska cesta 29, 10000 Zagreb, Croatia
| | - Dina Rešetar Maslov
- Laboratory of Proteomics, Clinic for Internal Diseases, Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55, 10000 Zagreb, Croatia
| | - Josipa Kuleš
- Department of Chemistry and Biochemistry, Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55, 10000 Zagreb, Croatia
| | - Marina Roje Bedeković
- Department of Neurology, University Hospital Centre “Sestre Milosrdnice”, Vinogradska cesta 29, 10000 Zagreb, Croatia
| | - Tomislav Sajko
- Department of Neurosurgery, University Hospital Centre “Sestre Milosrdnice”, Vinogradska cesta 29, 10000 Zagreb, Croatia
| | - Krešimir Rotim
- Department of Neurosurgery, University Hospital Centre “Sestre Milosrdnice”, Vinogradska cesta 29, 10000 Zagreb, Croatia
| | - Vladimir Mrljak
- Laboratory of Proteomics, Clinic for Internal Diseases, Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55, 10000 Zagreb, Croatia
| | - Dragana Fabris
- Department of Medical Chemistry, Biochemistry and Clinical Chemistry, School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia
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Dar OI, Vinothkanna A, Aslam B, Furkh A, Sharma S, Kaur A, Gao YA, Jia AQ. Dynamic alterations in physiological and biochemical indicators of Cirrhinus mrigala hatchlings: A sublethal exposure of triclosan. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 924:171701. [PMID: 38490412 DOI: 10.1016/j.scitotenv.2024.171701] [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: 12/20/2023] [Revised: 02/11/2024] [Accepted: 03/11/2024] [Indexed: 03/17/2024]
Abstract
Triclosan (TCS), a biocide used in various day-to-day products, has been associated with several toxic effects in aquatic organisms. In the present study, biochemical and hematological alterations were evaluated after 14 d (sublethal) exposure of tap water (control), acetone (solvent control), 5, 10, 20, and 50 μg/L (environmentally relevant concentrations) TCS to the embryos/hatchlings of Cirrhinus mrigala, a major freshwater carp distributed in tropic and sub-tropical areas of Asia. A concentration-dependent increase in the content of urea and protein carbonyl, while a decrease in the total protein, glucose, cholesterol, triglycerides, uric acid, and bilirubin was observed after the exposure. Hematological analysis revealed a decrease in the total erythrocyte count, hemoglobin, and partial pressure of oxygen, while there was an increase in the total leucocyte count, carbon dioxide, and partial pressure of carbon dioxide and serum electrolytes. Comet assay demonstrates a concentration-dependent increase in tail length, tail moment, olive tail moment, and percent tail DNA. An amino acid analyzer showed a TCS-dose-dependent increase in various amino acids. Sodium dodecyl sulphate polyacrylamide gel electrophoresis analysis revealed different proteins ranging from 6.5 to 200 kDa, demonstrating TCS-induced upregulation. Fourier transform infrared spectra analysis exhibited a decline in peak area percents with an increase in the concentration of TCS in water. Curve fitting of amide I (1,700-1600 cm-1) showed a decline in α-helix and turns and an increase in β-sheets. Nuclear magnetic resonance study also revealed concentration-dependent alterations in the metabolites after 14 d exposure. TCS caused alterations in the biomolecules and heamatological parameters of fish, raising the possibility that small amounts of TCS may change the species richness in natural aquatic habitats. In addition, consuming TCS-contaminated fish may have detrimental effects on human health. Consequently, there is a need for the proper utilisation and disposal of this hazardous compound in legitimate quantities.
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Affiliation(s)
- Owias Iqbal Dar
- Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570311, China; Key Laboratory of Ministry of Education for Advanced Materials in Tropical Island Resources, Hainan University, Haikou 570228, China.
| | - Annadurai Vinothkanna
- Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570311, China; Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Life and Health Sciences, Hainan University, Haikou 570228, China
| | - Bisma Aslam
- Department of Biochemistry, University of Kashmir, Srinagar, Jammu and Kashmir 190006, India
| | - Arajmand Furkh
- Department of Botany, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India
| | - Sunil Sharma
- Aquatic Toxicology Lab, Department of Zoology, Guru Nanak Dev University, Amritsar, Punjab 143005, India
| | - Arvinder Kaur
- Aquatic Toxicology Lab, Department of Zoology, Guru Nanak Dev University, Amritsar, Punjab 143005, India
| | - Yan-An Gao
- Key Laboratory of Ministry of Education for Advanced Materials in Tropical Island Resources, Hainan University, Haikou 570228, China
| | - Ai-Qun Jia
- Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570311, China.
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Yadav S, Kumar A, Singh S, Ahmad S, Singh G, Khan AR, Chaurasia RN, Kumar D. NMR based Serum metabolomics revealed metabolic signatures associated with oxidative stress and mitochondrial damage in brain stroke. Metab Brain Dis 2024; 39:283-294. [PMID: 38095788 DOI: 10.1007/s11011-023-01331-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 11/22/2023] [Indexed: 02/02/2024]
Abstract
Brain stroke (BS, also known as a cerebrovascular accident), represents a serious global health crisis. It has been a leading cause of permanent disability and unfortunately, frequent fatalities due to lack of timely medical intervention. While progress has been made in prevention and management, the complexities and consequences of stroke continue to pose significant challenges, especially, its impact on patient's quality of life and independence. During stroke, there is a substantial decrease in oxygen supply to the brain leading to alteration of cellular metabolic pathways, including those involved in mitochondrial-damage, leading to mitochondrial-dysfunction. The present proof-of-the-concept metabolomics study has been performed to gain insights into the metabolic pathways altered following a brain stroke and discover new potential targets for timely interventions to mitigate the effects of cellular and mitochondrial damage in BS. The serum metabolic profiles of 108 BS-patients were measured using 800 MHz NMR spectroscopy and compared with 60 age and sex matched normal control (NC) subjects. Compared to NC, the serum levels of glutamate, TCA-cycle intermediates (such as citrate, succinate, etc.), and membrane metabolites (betaine, choline, etc.) were found to be decreased BS patients, whereas those of methionine, mannose, mannitol, phenylalanine, urea, creatine and organic acids (such as 3-hydroxybutyrate and acetone) were found to be elevated in BS patients. These metabolic changes hinted towards hypoxia mediated mitochondrial dysfunction in BS-patients. Further, the area under receiver operating characteristic curve (ROC) values for five metabolic features (methionine, mannitol, phenylalanine, mannose and urea) found to be more than 0.9 suggesting their high sensitivity and specificity for differentiating BS from NC subjects.
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Affiliation(s)
- Sachin Yadav
- Department of Chemistry, Integral University, Lucknow, 226026, India
| | - Abhai Kumar
- Department of Botany, Deen Dayal Upadhyaya Gorakhpur University, Gorakhpur, 273009, Uttar Pradesh, India.
| | - Smita Singh
- Department of Zoology, Dayal Upadhyaya Gorakhpur University, Gorakhpur, 273009, Uttar Pradesh, India
| | - Shahnawaz Ahmad
- Department of Neurology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India
| | - Gurvinder Singh
- Centre of Biomedical Research (CBMR), SGPGIMS Campus, Lucknow, 226014, Uttar Pradesh, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India
| | - Abdul Rahman Khan
- Department of Chemistry, Integral University, Lucknow, 226026, India
| | - Rameshwar Nath Chaurasia
- Department of Neurology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India.
| | - Dinesh Kumar
- Centre of Biomedical Research (CBMR), SGPGIMS Campus, Lucknow, 226014, Uttar Pradesh, India.
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Liu R, Cao S, Cai Y, Zhou M, Gou X, Huang Y. Brain and serum metabolomic studies reveal therapeutic effects of san hua decoction in rats with ischemic stroke. Front Endocrinol (Lausanne) 2023; 14:1289558. [PMID: 38098862 PMCID: PMC10720749 DOI: 10.3389/fendo.2023.1289558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 11/13/2023] [Indexed: 12/17/2023] Open
Abstract
San Hua Decoction (SHD) is a traditional four-herbal formula that has long been used to treat stroke. Our study used a traditional pharmacodynamic approach combined with systematic and untargeted metabolomics analyses to further investigate the therapeutic effects and potential mechanisms of SHD on ischemic stroke (IS). Male Sprague-Dawley rats were randomly divided into control, sham-operated, middle cerebral artery occlusion reperfusion (MCAO/R) model and SHD groups. The SHD group was provided with SHD (7.2 g/kg, i.g.) and the other three groups were provided with equal amounts of purified water once a day in the morning for 10 consecutive days. Our results showed that cerebral infarct volumes were reduced in the SHD group compared with the model group. Besides, SHD enhanced the activity of SOD and decreased MDA level in MCAO/R rats. Meanwhile, SHD could ameliorate pathological abnormalities by reducing neuronal damage, improving the structure of damaged neurons and reducing inflammatory cell infiltration. Metabolomic analysis of brain and serum samples with GC-MS techniques revealed 55 differential metabolites between the sham and model groups. Among them, the levels of 12 metabolites were restored after treatment with SHD. Metabolic pathway analysis showed that SHD improved the levels of 12 metabolites related to amino acid metabolism and carbohydrate metabolism, 9 of which were significantly associated with disease. SHD attenuated brain inflammation after ischemia-reperfusion. The mechanisms underlying the therapeutic effects of SHD in MCAO/R rats are related to amino acid and carbohydrate metabolism.
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Affiliation(s)
- Ruisi Liu
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Shengxuan Cao
- Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing Key Laboratory of Research of Chinese Medicine on Prevention and Treatment for Major Diseases, Beijing, China
| | - Yufeng Cai
- Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing Key Laboratory of Research of Chinese Medicine on Prevention and Treatment for Major Diseases, Beijing, China
| | - Mingmei Zhou
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai Frontiers Science Center of TCM Chemical Biology, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiaojun Gou
- Central Laboratory, Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ying Huang
- Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing Key Laboratory of Research of Chinese Medicine on Prevention and Treatment for Major Diseases, Beijing, China
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Oliveira N, Sousa A, Amaral AP, Graça G, Verde I. Searching for Metabolic Markers of Stroke in Human Plasma via NMR Analysis. Int J Mol Sci 2023; 24:16173. [PMID: 38003362 PMCID: PMC10671802 DOI: 10.3390/ijms242216173] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Revised: 10/31/2023] [Accepted: 11/08/2023] [Indexed: 11/26/2023] Open
Abstract
More than 12 million people around the world suffer a stroke every year, one every 3 s. Stroke has a variety of causes and is often the result of a complex interaction of risk factors related to age, genetics, gender, lifestyle, and some cardiovascular and metabolic diseases. Despite this evidence, it is not possible to prevent the onset of stroke. The use of innovative methods for metabolite analysis has been explored in the last years to detect new stroke biomarkers. We use NMR spectroscopy to identify small molecule variations between different stages of stroke risk. The Framingham Stroke Risk Score was used in people over 63 years of age living in long-term care facilities (LTCF) to calculate the probability of suffering a stroke. Using this parameter, three study groups were formed: low stroke risk (LSR, control), moderate stroke risk (MSR) and high stroke risk (HSR). Univariate statistical analysis showed seven metabolites with increasing plasma levels across different stroke risk groups, from LSR to HSR: isoleucine, asparagine, formate, creatinine, dimethylsulfone and two unidentified molecules, which we termed "unknown-1" and "unknown-3". These metabolic markers can be used for early detection and to detect increasing stages of stroke risk more efficiently.
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Affiliation(s)
- Nádia Oliveira
- Health Sciences Research Centre (CICS-UBI), University of Beira Interior (UBI), Av. Infante D. Henrique, 6200-506 Covilha, Portugal; (N.O.); (A.S.); (A.P.A.)
| | - Adriana Sousa
- Health Sciences Research Centre (CICS-UBI), University of Beira Interior (UBI), Av. Infante D. Henrique, 6200-506 Covilha, Portugal; (N.O.); (A.S.); (A.P.A.)
| | - Ana Paula Amaral
- Health Sciences Research Centre (CICS-UBI), University of Beira Interior (UBI), Av. Infante D. Henrique, 6200-506 Covilha, Portugal; (N.O.); (A.S.); (A.P.A.)
| | - Gonçalo Graça
- Section of Bioinformatics, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
| | - Ignacio Verde
- Health Sciences Research Centre (CICS-UBI), University of Beira Interior (UBI), Av. Infante D. Henrique, 6200-506 Covilha, Portugal; (N.O.); (A.S.); (A.P.A.)
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