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Nandi A, Singh K, Sharma K. Advancement in early diagnosis of polycystic ovary syndrome: biomarker-driven innovative diagnostic sensor. Mikrochim Acta 2025; 192:331. [PMID: 40310524 DOI: 10.1007/s00604-025-07187-w] [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: 02/21/2025] [Accepted: 04/22/2025] [Indexed: 05/02/2025]
Abstract
Polycystic ovary syndrome (PCOS) is a heterogeneous multifactorial endocrine disorder that affects one in five women around the globe. The pathology suggests a strong polygenic and epigenetic correlation, along with hormonal and metabolic dysfunction, but the exact etiology is still a mystery. The current diagnosis is mostly based on Rotterdam criteria, which resulted in a delayed diagnosis in most of the cases, leading to unbearable lifestyle complications and infertility. PCOS is not new; thus, constant efforts are made in the field of biomarker discovery and advanced diagnostic techniques. A plethora of research has enabled the identification of promising PCOS diagnostic biomarkers across hormonal, metabolic, genetic, and epigenetic domains. Not only biomarker identification, but the utilization of biosensing platforms also renders effective point-of-care diagnostic devices. Artificial intelligence also shows its power in modifying existing image-based analysis, even developing symptom-based prediction systems for the early diagnosis of this multifaceted disorder. This approach could affect the future management and treatment direction of PCOS, decreasing its severity and improving the reproductive life of women. The rationale of the current review is to identify the advancements in understanding the pathophysiology through biomarker discovery and the implementation of modern analytical techniques for the early diagnosis of PCOS.
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Affiliation(s)
- Aniket Nandi
- Department of Pharmaceutical Chemistry and Analysis, ISF College of Pharmacy, G.T Road, Ghal Kalan, Moga, Punjab, 142001, India
| | - Kamal Singh
- Bond Life Sciences Center, and Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, 65211, USA
| | - Kalicharan Sharma
- Department of Pharmaceutical Chemistry and Analysis, ISF College of Pharmacy, G.T Road, Ghal Kalan, Moga, Punjab, 142001, India.
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Chen M, Liu G, Wang L, Zhang A, Yang Z, Li X, Zhang Z, Gu S, Cui D, Haick H, Tang N. Neural Network-Enhanced Electrochemical/SERS Dual-Mode Microfluidic Platform for Accurate Detection of Interleukin-6 in Diabetic Wound Exudates. Anal Chem 2025; 97:4397-4406. [PMID: 39985433 DOI: 10.1021/acs.analchem.4c05537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2025]
Abstract
Interleukin-6 (IL-6) plays a pivotal role in the inflammatory response of diabetic wounds, providing critical insights for clinicians in the development of personalized treatment strategies. However, the low concentration of IL-6 in biological samples, coupled with the presence of numerous interfering substances, poses a significant challenge for its rapid and accurate detection. Herein, we present a dual-mode microfluidic platform integrating electrochemical (EC) and surface-enhanced Raman spectroscopy (SERS) to achieve the timely and highly reliable quantification of IL-6. Efficient binding between IL-6 and antibody-conjugated SERS nanoprobes is obtained through a square-wave micromixer with nonleaky obstacles, forming sandwich immunocomplexes with IL-6 capture antibodies on the working electrode in the detection area, enabling acquisition of both EC and SERS signals. This microfluidic platform demonstrates excellent selectivity and sensitivity, with detection limits of 0.085 and 0.047 pg/mL for EC and SERS modes, respectively. Importantly, by incorporating a neural network (NN) with a self-attention (SA) mechanism to evaluate the relative weights of data from both modes, the platform achieves a quantitative accuracy of up to 99.8% across a range of 0.05-1000 pg/mL, demonstrating significant performance at low concentrations. Moreover, the NN-enhanced dual-mode microfluidic platform effectively detects IL-6 in diabetic wound exudates with results that align closely with clinical data. This integrated dual-mode microfluidic platform offers promising potential for the rapid and accurate detection of cytokines.
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Affiliation(s)
- Mingrui Chen
- School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Guan Liu
- School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Li Wang
- Precision Research Center for Refractory Diseases in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China
| | - Amin Zhang
- School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Ziyang Yang
- School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Xia Li
- Trauma Center in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China
| | - Zhong Zhang
- Trauma Center in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China
| | - Song Gu
- Trauma Center in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China
| | - Daxiang Cui
- School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Hossam Haick
- Department of Chemical Engineering and Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa 3200003, Israel
| | - Ning Tang
- Precision Research Center for Refractory Diseases in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China
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Islam MA, Masson JF. Plasmonic Biosensors for Health Monitoring: Inflammation Biomarker Detection. ACS Sens 2025; 10:577-601. [PMID: 39917878 DOI: 10.1021/acssensors.4c03562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2025]
Abstract
Surface plasmon resonance (SPR) and localized SPR (LSPR) biosensors have emerged as viable technologies in the clinical detection of biomarkers for a wide array of health conditions. The success of SPR biosensors lies in their ability to monitor in real-time label-free biomarkers in complex biofluids. Recent breakthroughs in nanotechnology and surface chemistry have significantly improved this feature, notably from the incorporation of advanced nanomaterials including gold nanoparticles, graphene, and carbon nanotubes providing better SPR sensor performance in terms of detection limits, stability, and specificity. Recent progress in microfluidic integration has enabled SPR biosensors to detect multiple biomarkers simultaneously in complex biological samples. Taken together, these advances are closing the gap for their use in clinical diagnostics and point-of-care (POC) applications. While broadly applicable, the latest advancements in plasmonic biosensing are overviewed using inflammation biomarkers C-reactive protein (CRP), interleukins (ILs), tumor necrosis factor-α (TNF-α), procalcitonin (PCT), ferritin, and fibrinogen for a series of conditions, including cardiovascular diseases, autoimmune disorders, infections, and sepsis, as a key example of plasmonic biosensors for clinical applications. We highlight developments in sensor design, nanomaterial integration, surface functionalization, and multiplexing and provide a look forward to clinical applications by assessing the current limitations and exploring future directions for translating SPR biosensors for diagnostics and health monitoring. By enhancement of diagnostic accuracy, reproducibility, and accessibility, particularly in POC settings, SPR biosensors have the potential to significantly contribute to personalized healthcare and bring real-time, high-precision diagnostics to the forefront of clinical practice.
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Affiliation(s)
- M Amirul Islam
- Département de Chimie, Institut Courtois, Centre Interdisciplinaire de Recherche sur le Cerveau et l'Apprentissage, Quebec Center for Advanced Materials, Regroupement Québécois sur les Matériaux de Pointe, Université de Montréal, C.P. 6128 Succ. Centre-ville, Montréal, Québec H3C 3J7, Canada
| | - Jean-François Masson
- Département de Chimie, Institut Courtois, Centre Interdisciplinaire de Recherche sur le Cerveau et l'Apprentissage, Quebec Center for Advanced Materials, Regroupement Québécois sur les Matériaux de Pointe, Université de Montréal, C.P. 6128 Succ. Centre-ville, Montréal, Québec H3C 3J7, Canada
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Du H, Li K, Guo W, Na M, Zhang J, Na R. Maternal Roughage Sources Influence the Gastrointestinal Development of Goat Kids by Modulating the Colonization of Gastrointestinal Microbiota. Animals (Basel) 2025; 15:393. [PMID: 39943163 PMCID: PMC11815875 DOI: 10.3390/ani15030393] [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: 12/12/2024] [Revised: 01/27/2025] [Accepted: 01/28/2025] [Indexed: 02/16/2025] Open
Abstract
During pregnancy and lactation, maternal nutrition is linked to the full development of offspring and may have long-term or lifelong effects. However, the influence of the doe's diet on the gastrointestinal (GI) tract of young kids remains largely unexplored. Therefore, we investigated the effects of doe roughage sources (alfalfa hay, AH, or corn straw, CS) during pregnancy and lactation on kid growth, GI morphology, barrier function, metabolism, immunity, and microbiome composition. The results indicate that, compared with the CS group, does fed an AH diet had significantly higher feed intake (p < 0.01). However, CS-fed does exhibited higher neutral detergent fiber (NDF) digestibility (p < 0.05). There were no significant differences in animal (doe or kid) weight among the groups (p > 0.05). In the rumen of goat kids, the AH group exhibited a higher papillae width and increased levels of interleukin-10 (IL-10) compared with the CS group (p < 0.05). In the jejunum of goat kids, the AH group showed a higher villus-height-to-crypt-depth (VH/CD) ratio, as well as elevated levels of secretory immunoglobulin A (SIgA), immunoglobulin G (IgG), IL-10, acetate, and total volatile fatty acids (TVFAs), when compared with the CS group (p < 0.05). Transcriptome analysis revealed that the source of roughage in does was associated with changes in the GI transcriptome of the kids. Differentially expressed genes (DEGs) in the rumen were mainly associated with tissue development and immune regulation, while the DEGs in the jejunum were mainly associated with the regulation of transferase activity. Spearman correlation analyses indicated significant associations between GI DEGs and phenotypic indicators related to GI development, immunity, and metabolism. LEfSe analysis identified 14 rumen microbial biomarkers and 6 jejunum microbial biomarkers. Notably, these microorganisms were also enriched in the rumen or day 28 milk of the does. Further microbial composition analysis revealed significant correlations between the rumen and milk microbiomes of does and the rumen or jejunum microbiomes of kids. Association analyses indicated that microbial biomarkers interact with host genes, thereby affecting the development and function of the GI system. Additionally, correlation analyses revealed significant association between milk metabolites and the rumen and jejunum microbiomes of kids. This study demonstrated that maternal diet significantly influences the development of microbial ecosystems in offspring by modulating microbial communities and metabolite composition. The early colonization of GI microorganisms is crucial for the structural development, barrier function, immune capacity, and microbial metabolic activity of the GI system.
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Affiliation(s)
- Haidong Du
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China; (H.D.); (W.G.); (M.N.); (J.Z.)
| | - Kenan Li
- Grassland Research Institute of Chinese Academy of Agricultural Sciences, Hohhot 010010, China;
| | - Wenliang Guo
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China; (H.D.); (W.G.); (M.N.); (J.Z.)
| | - Meila Na
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China; (H.D.); (W.G.); (M.N.); (J.Z.)
| | - Jing Zhang
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China; (H.D.); (W.G.); (M.N.); (J.Z.)
| | - Renhua Na
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China; (H.D.); (W.G.); (M.N.); (J.Z.)
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Shakeri A, Najm L, Khan S, Tian L, Ladouceur L, Sidhu H, Al-Jabouri N, Hosseinidoust Z, Didar TF. Noncontact 3D Bioprinting of Proteinaceous Microarrays for Highly Sensitive Immunofluorescence Detection within Clinical Samples. ACS NANO 2024; 18:31506-31523. [PMID: 39468857 DOI: 10.1021/acsnano.4c12460] [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: 10/30/2024]
Abstract
Immunofluorescence assays are extensively used for the detection of disease-associated biomarkers within patient samples for direct diagnosis. Unfortunately, these 2D microarrays suffer from low repeatability and fail to attain the low limits of detection (LODs) required to accurately discern disease progression for clinical monitoring. While three-dimensional microarrays with increased biorecognition molecule density stand to circumvent these limitations, their viscous component materials are not compatible with current microarray fabrication protocols. Herein, we introduce a platform for 3D microarray bioprinting, wherein a two-step printing approach enables the high-throughput fabrication of immunosorbent hydrogels. The hydrogels are composed entirely of cross-linked proteins decorated with clinically relevant capture antibodies. Compared to two-dimensional microarrays, these proteinaceous microarrays offer 3-fold increases in signal intensity. When tested with clinically relevant biomarkers, ultrasensitive single-plex and multiplex detection of interleukin-6 (LOD 0.3 pg/mL) and tumor necrosis factor receptor 1 (LOD 1 pg/mL) is observed. When challenged with clinical samples, these hydrogel microarrays consistently discern elevated levels of interleukin-6 in blood plasma derived from patients with systemic blood infections. Given their easy-to-implement, high-throughput fabrication, and ultrasensitive detection, these three-dimensional microarrays will enable better clinical monitoring of disease progression, yielding improved patient outcomes.
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Affiliation(s)
- Amid Shakeri
- Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada M5S 3G9
| | - Lubna Najm
- School of Biomedical Engineering, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4L8
| | - Shadman Khan
- School of Biomedical Engineering, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4L8
| | - Lei Tian
- Department of Chemical Engineering, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4L8
| | - Liane Ladouceur
- Department of Mechanical Engineering, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4L8
| | - Hareet Sidhu
- Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4K1
| | - Nadine Al-Jabouri
- Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4K1
| | - Zeinab Hosseinidoust
- School of Biomedical Engineering, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4L8
- Department of Chemical Engineering, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4L8
- Institute for Infectious Disease Research (IIDR), 1280 Main St W, McMaster University, Hamilton, Ontario, Canada L8S 4L8
- Farncombe Family Digestive Health Research Institute, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4K1
| | - Tohid F Didar
- School of Biomedical Engineering, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4L8
- Department of Mechanical Engineering, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4L8
- Institute for Infectious Disease Research (IIDR), 1280 Main St W, McMaster University, Hamilton, Ontario, Canada L8S 4L8
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Bhalerao KS, De Silva PIT, Hiniduma K, Grunbaum A, Rozza N, Kremer R, Rusling JF. Microfluidic Immunoarray for Point-of-Care Detection of Cytokines in COVID-19 Patients. ACS OMEGA 2024; 9:29320-29330. [PMID: 39005811 PMCID: PMC11238202 DOI: 10.1021/acsomega.4c00735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 06/03/2024] [Accepted: 06/10/2024] [Indexed: 07/16/2024]
Abstract
The "cytokine storm" often induced in COVID-19 patients contributes to the onset of "acute respiratory distress syndrome" (ARDS) accompanied by lung infection and damage, multiorgan failure, and even death. This large increase in pro-inflammatory cytokines in blood may be related to severity. Rapid, on-demand cytokine analyses can thus be critical to inform treatment plans and improve survival rates. Here, we report a sensitive, low-cost, semiautomated 3D-printed microfluidic immunoarray to detect 2 cytokines and CRP simultaneously in a single 10 μL serum sample in 25 min. Accuracy was validated by analyzing 80 COVID-19 patient serum samples, with results well correlated to a commercial Meso Scale protein immunoassay. Capture antibodies immobilized in detection microwells in a flat well plate-type flow chamber facilitate the immunoassay, with a programmable syringe pump automatically delivering reagents. Chemiluminescence signals were captured in a dark box with a CCD camera integrated for 30 s. This system was optimized to detect inflammation biomarkers IL-6, IFN-γ, and CRP simultaneously in blood serum. Ultralow limits of detection (LODs) of 0.79 fg/mL for IL-6, 4.2 fg/mL for CRP, and 2.7 fg/mL for IFN-γ with dynamic ranges of up to 100 pg/mL were achieved. ROC statistical analyses showed a relatively good diagnostic value related to the samples assigned WHO COVID-19 scores for disease severity, with the best results for IL-6 and CRP. Monitoring these biomarkers for coronavirus severity may allow prediction of disease severity as a basis for critical treatment decisions and better survival rates.
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Affiliation(s)
- Ketki S Bhalerao
- Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States
| | - P I Thilini De Silva
- Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States
| | - Keshani Hiniduma
- Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States
| | - Ami Grunbaum
- Department of Medicine, McGill University Health Centre, 1001 Decarie Blvd., Montreal, QC H3A 1A1, Canada
| | - Nicholas Rozza
- Department of Medicine, McGill University Health Centre, 1001 Decarie Blvd., Montreal, QC H3A 1A1, Canada
| | - Richard Kremer
- Department of Medicine, McGill University Health Centre, 1001 Decarie Blvd., Montreal, QC H3A 1A1, Canada
| | - James F Rusling
- Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States
- Institute of Material Science, University of Connecticut, Storrs, Connecticut 06269, United States
- School of Chemistry, National University of Ireland at Galway, Galway H91 TK33, Ireland
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7
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Tang L, Cai S, Lu X, Wu D, Zhang Y, Li X, Qin X, Guo J, Zhang X, Liu C. Platelet-Derived Growth Factor Nanocapsules with Tunable Controlled Release for Chronic Wound Healing. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2310743. [PMID: 38263812 DOI: 10.1002/smll.202310743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 01/11/2024] [Indexed: 01/25/2024]
Abstract
Chronic wounds have emerged as an increasingly critical clinical challenge over the past few decades, due to their increasing incidence and socioeconomic burdens. Platelet-derived growth factor (PDGF) plays a pivotal role in regulating processes such as fibroblast migration, proliferation, and vascular formation during the wound healing process. The delivery of PDGF offers great potential for expediting the healing of chronic wounds. However, the clinical effectiveness of PDGF in chronic wound healing is significantly hampered by its inability to maintain a stable concentration at the wound site over an extended period. In this study, a controlled PDGF delivery system based on nanocapsules is proposed. In this system, PDGF is encapsulated within a degradable polymer shell. The release rate of PDGF from these nanocapsules can be precisely adjusted by controlling the ratios of two crosslinkers with different degradation rates within the shells. As demonstrated in a diabetic wound model, improved therapeutic outcomes with PDGF nanocapsules (nPDGF) treatment are observed. This research introduces a novel PDGF delivery platform that holds promise for enhancing the effectiveness of chronic wound healing.
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Affiliation(s)
- Lin Tang
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, P. R. China
| | - Susu Cai
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, P. R. China
| | - Xing Lu
- Beijing Institute of Biotechnology, Beijing, 100071, P. R. China
| | - Dingqi Wu
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, P. R. China
| | - Yahan Zhang
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, P. R. China
| | - Xiaoming Li
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, P. R. China
| | - Xiaoyan Qin
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, P. R. China
| | - Jimin Guo
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, P. R. China
| | - Xiaopeng Zhang
- Beijing Institute of Biotechnology, Beijing, 100071, P. R. China
| | - Chaoyong Liu
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, P. R. China
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, P. R. China
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Yang HJ, Raju CV, Choi CH, Park JP. Electrochemical peptide-based biosensor for the detection of the inflammatory disease biomarker, interleukin-1beta. Anal Chim Acta 2024; 1295:342287. [PMID: 38355228 DOI: 10.1016/j.aca.2024.342287] [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: 11/07/2023] [Revised: 12/20/2023] [Accepted: 01/24/2024] [Indexed: 02/16/2024]
Abstract
This paper reports the development of a highly sensitive and selective electrochemical peptide-based biosensor for the detection of the inflammatory disease biomarker, interleukin-1beta (IL-1β). To this end, flower-like Au-Ag@MoS2-rGO nanocomposites were used as the signal amplification platform to achieve a label-free biosensor with a high sensitivity and selectivity. First, a high-affinity peptide for IL-1β was identified through biopanning with M13 random peptide libraries, and was newly designed by incorporating cysteine at the C-terminus. An IL-1β specific binding peptide was used as the bio-receptor, and the interaction between the IL-1β binding peptide and IL-1β was confirmed via enzyme-linked immunosorbent assay and various physicochemical and electrochemical analyses. Under optimal conditions, the biosensor achieved an ultrasensitive and specific IL-1β detection in a wide linear concentration range of 0-250 ng/mL with a picomolar-level detection limit (∼2.4 pM), low binding constant (∼0.62 pM), and a low coefficient of variation (<1.65 %). The biosensor was successfully utilized for IL-1β determination in the serum of Crohn's disease patients with a good correlation coefficient. In addition, the detection performance was comparable to that of commercially available IL-1β ELISA kit. This indicates that the electrochemical peptide-based biosensor may offer a potentially valuable platform for the clinical diagnosis of various inflammatory disease biomarkers.
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Affiliation(s)
- Hyo Jeong Yang
- Basic Research Laboratory, Department of Food Science and Technology and GreenTech-based Food Safety Research Group, BK21 Four, Chung-Ang University, Anseong, 17546, Republic of Korea
| | - Chikkili Venkateswara Raju
- Basic Research Laboratory, Department of Food Science and Technology and GreenTech-based Food Safety Research Group, BK21 Four, Chung-Ang University, Anseong, 17546, Republic of Korea
| | - Chang-Hyung Choi
- School of Chemical Engineering, Yeungnam University, 280 Daehak-ro, Gyeongsan, Gyeongbuk, 38541, Republic of Korea
| | - Jong Pil Park
- Basic Research Laboratory, Department of Food Science and Technology and GreenTech-based Food Safety Research Group, BK21 Four, Chung-Ang University, Anseong, 17546, Republic of Korea.
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9
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Li S, Guo H, Gao Y, Tian W, Wang S, Shen C, Xu L, Liu H, Zhang J, Wang Y. Development of a free cytokine immunoassay to maintain binding and dissociation equilibrium in vitro. J Pharm Biomed Anal 2024; 238:115813. [PMID: 37956554 DOI: 10.1016/j.jpba.2023.115813] [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: 07/31/2023] [Revised: 10/18/2023] [Accepted: 10/22/2023] [Indexed: 11/15/2023]
Abstract
Using competitive ELISA to detect free cytokines is limited as it can only reflect relative trends rather than accurately determine the real state and quantity of cytokines due to the dynamic equilibrium between dissociation and binding. This imprecise quantification adversely affects the usage of clinical medication and the validity assessment. In this study, we have developed a novel cytokine immunoassay that utilizes Rosetta molecular docking prediction technique, we screened two specific antibody pairs binding IL-1β and Durg respectively and then established the Total IL-1β and Total Drug ELISA assay. Protein A column could separate bound IL-1β and free IL-1β, and the bound IL-1β occupied for about 90% of the total. This innovative approach ensures the maintenance of equilibrium between the free cytokines and complex. We have developed a free cytokine content detection method that combines ELISA and solid phase extraction, which can detect the true concentration of free cytokines without destroying the free-binding dynamic equilibrium. It can be used to verify the accuracy of clinical PK/PD and other data, evaluate the applicability of detection methods, and guide clinical drug use and drug efficacy evaluation.
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Affiliation(s)
- Siqi Li
- GeneScience Pharmaceuticals Co, Ltd, Changchun 130012, China
| | - Hao Guo
- GeneScience Pharmaceuticals Co, Ltd, Changchun 130012, China
| | - Yan Gao
- GeneScience Pharmaceuticals Co, Ltd, Changchun 130012, China
| | - Wen Tian
- GeneScience Pharmaceuticals Co, Ltd, Changchun 130012, China
| | - Shan Wang
- GeneScience Pharmaceuticals Co, Ltd, Changchun 130012, China
| | - Chen Shen
- GeneScience Pharmaceuticals Co, Ltd, Changchun 130012, China
| | - Lili Xu
- GeneScience Pharmaceuticals Co, Ltd, Changchun 130012, China
| | - Hailong Liu
- GeneScience Pharmaceuticals Co, Ltd, Changchun 130012, China
| | - Jinliang Zhang
- School of Life Science, Jilin University, Changchun 130012, China; GeneScience Pharmaceuticals Co, Ltd, Changchun 130012, China
| | - Yingwu Wang
- School of Life Science, Jilin University, Changchun 130012, China; Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun 130012, China.
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10
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Ali SB, Cecchin A, Lucchesi C, Putty T, Edwards S, Petrou T, Coates P, Ferrante A, Pucar PA, King J, Banovic T. Can C-reactive protein be used as a surrogate marker of IL-6 in a broad array of clinical entities? Biomark Med 2023; 17:1001-1010. [PMID: 38235562 DOI: 10.2217/bmm-2023-0708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2024] Open
Abstract
Background: C-reactive protein (CRP) is commonly performed, whereas cytokine testing is limited to research. Aims: To determine CRP correlation to cytokines IL-6, IL-1β and TNF-α. Results: Consecutive samples (n = 307) were collected over 24 h. Ninety-six patients (31%) had acute infections, and 23 patients (7.5%) had autoimmune or inflammatory disease presentations. A strong correlation between CRP and two IL-6 assays (r = 0.74 and r = 0.71; p < 0.001) was present. CRP did not correlate with IL-1β and TNF-α across the data set. Bacterial infection had a significantly higher CRP and IL-6 (p < 0.001), while only CRP was elevated in inflammatory and autoimmune diseases (p < 0.001). Discussion: CRP may be used as a surrogate marker of IL-6 levels in the routine diagnostic laboratories.
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Affiliation(s)
- Syed B Ali
- Department of Clinical Immunology & Allergy, Royal Adelaide Hospital, Adelaide, South Australia, 5000, Australia
- Department of Immunopathology, Adelaide, 5000, Australia
- School of Medicine & Public Health, University of Adelaide, 5000, Australia
| | - Amelia Cecchin
- Department of Immunopathology, Adelaide, 5000, Australia
| | | | - Trishni Putty
- Department of Immunopathology, SA Pathology Womens' & Childrens' Hospital, Adelaide, 5000, Australia
| | - Suzanne Edwards
- Adelaide Health Technology Assessment, School of Public Health, University of Adelaide, Adelaide, 5000, Australia
| | - Tina Petrou
- Department of Biochemistry, Royal Adelaide Hospital, Adelaide, 5000, Australia
| | - Penelope Coates
- Department of Biochemistry, Royal Adelaide Hospital, Adelaide, 5000, Australia
- Department of Biochemistry, SA Pathology, Adelaide, 5000, Australia
| | - Antonio Ferrante
- Department of Immunopathology, SA Pathology Womens' & Childrens' Hospital, Adelaide, 5000, Australia
| | - Phillippa A Pucar
- Department of Clinical Immunology & Allergy, Royal Adelaide Hospital, Adelaide, South Australia, 5000, Australia
- Department of Immunopathology, Adelaide, 5000, Australia
| | - Jovanka King
- Department of Immunopathology, Adelaide, 5000, Australia
- School of Medicine & Public Health, University of Adelaide, 5000, Australia
- Department of Immunopathology, SA Pathology Womens' & Childrens' Hospital, Adelaide, 5000, Australia
| | - Tatjana Banovic
- Department of Clinical Immunology & Allergy, Royal Adelaide Hospital, Adelaide, South Australia, 5000, Australia
- Department of Immunopathology, Adelaide, 5000, Australia
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11
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Haller N, Reichel T, Zimmer P, Behringer M, Wahl P, Stöggl T, Krüger K, Simon P. Blood-Based Biomarkers for Managing Workload in Athletes: Perspectives for Research on Emerging Biomarkers. Sports Med 2023; 53:2039-2053. [PMID: 37341908 PMCID: PMC10587296 DOI: 10.1007/s40279-023-01866-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/18/2023] [Indexed: 06/22/2023]
Abstract
At present, various blood-based biomarkers have found their applications in the field of sports medicine. This current opinion addresses biomarkers that warrant consideration in future research for monitoring the athlete training load. In this regard, we identified a variety of emerging load-sensitive biomarkers, e.g., cytokines (such as IL-6), chaperones (such as heat shock proteins) or enzymes (such as myeloperoxidase) that could improve future athlete load monitoring as they have shown meaningful increases in acute and chronic exercise settings. In some cases, they have even been linked to training status or performance characteristics. However, many of these markers have not been extensively studied and the cost and effort of measuring these parameters are still high, making them inconvenient for practitioners so far. We therefore outline strategies to improve knowledge of acute and chronic biomarker responses, including ideas for standardized study settings. In addition, we emphasize the need for methodological advances such as the development of minimally invasive point-of-care devices as well as statistical aspects related to the evaluation of these monitoring tools to make biomarkers suitable for regular load monitoring.
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Affiliation(s)
- Nils Haller
- Department of Sports Medicine, Rehabilitation and Disease Prevention, Johannes Gutenberg University of Mainz, Mainz, Germany
- Department of Sport and Exercise Science, University of Salzburg, Salzburg, Austria
| | - Thomas Reichel
- Department of Exercise Physiology and Sports Therapy, Institute of Sports Science, Justus-Liebig-University Gießen, Giessen, Germany
| | - Philipp Zimmer
- Division of Performance and Health (Sports Medicine), Institute for Sport and Sport Science, TU Dortmund University, Dortmund, Germany
| | - Michael Behringer
- Department of Sports Sciences, Goethe University Frankfurt, Frankfurt am Main, Germany
| | - Patrick Wahl
- Department of Exercise Physiology, German Sport University Cologne, Cologne, Germany
| | - Thomas Stöggl
- Department of Sport and Exercise Science, University of Salzburg, Salzburg, Austria
- Red Bull Athlete Performance Center, Salzburg, Austria
| | - Karsten Krüger
- Department of Exercise Physiology and Sports Therapy, Institute of Sports Science, Justus-Liebig-University Gießen, Giessen, Germany
| | - Perikles Simon
- Department of Sports Medicine, Rehabilitation and Disease Prevention, Johannes Gutenberg University of Mainz, Mainz, Germany.
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12
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Kotepui M, Duangchan T, Mahittikorn A, Mekhora C, Anabire NG, Kotepui KU. Interleukin-5 levels in relation to malaria severity: a systematic review. Malar J 2023; 22:226. [PMID: 37537570 PMCID: PMC10401852 DOI: 10.1186/s12936-023-04659-3] [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: 01/15/2023] [Accepted: 07/25/2023] [Indexed: 08/05/2023] Open
Abstract
BACKGROUND The role of cytokines such as interleukin-5 (IL-5) in the pathogenesis of malaria remains unclear. This systematic review sought to synthesize variations in IL-5 levels between severe and uncomplicated malaria, as well as between malaria and controls not afflicted with the disease. METHODS This systematic review was registered at the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022368773). Searches for studies that reported IL-5 levels in patients with malaria (any severity) and/or uninfected individuals were performed in Web of Science, PubMed, EMBASE, Scopus, CENTRAL, and MEDLINE, between 1st and 10th October, 2022. The risk of bias among all included studies was minimized using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for reporting observational studies. The differences in IL-5 levels between malaria and uninfected controls, and between severe and uncomplicated malaria were synthesized by narrative synthesis. RESULTS Among 1177 articles identified in the databases, 23 matched the eligibility criteria and were included in this systematic review. Qualitative syntheses showed the heterogeneity of IL-5 levels between different severities of clinical malaria and uninfected controls. The majority of the included studies (12/15 studies, 80%) found no change in IL-5 levels between malaria cases and uninfected controls. Similarly, most studies found no difference in IL-5 levels between severe (regardless of complications) and uncomplicated malaria (4/8 studies, 50%). The qualitative syntheses revealed that most studies found no difference in IL-5 levels between severe and non-severe malaria. CONCLUSIONS The comprehensive review suggests that IL-5 levels are unchanged in patients with different levels of clinical severity of malaria and uninfected controls. Given the limited number of published studies on IL-5 levels in malaria, there is a need for additional research to determine the function of this cytokine in the pathogenesis of malaria.
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Affiliation(s)
- Manas Kotepui
- Medical Technology Program, School of Allied Health Sciences, Walailak University, Tha Sala, Nakhon Si Thammarat, Thailand.
| | - Thitinat Duangchan
- Medical Technology Program, School of Allied Health Sciences, Walailak University, Tha Sala, Nakhon Si Thammarat, Thailand
| | - Aongart Mahittikorn
- Department of Protozoology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
| | - Chusana Mekhora
- Department of Nutrition and Health, Institute of Food Research and Product Development, Kasetsart University, Bangkok, Thailand
| | - Nsoh Godwin Anabire
- Department of Biochemistry & Molecular Medicine, School of Medicine, University for Development Studies, Tamale, Ghana
- Department of Biochemistry, Cell & Molecular Biology, West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra, Ghana
| | - Kwuntida Uthaisar Kotepui
- Medical Technology Program, School of Allied Health Sciences, Walailak University, Tha Sala, Nakhon Si Thammarat, Thailand
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13
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Boscarino G, Migliorino R, Carbone G, Davino G, Dell’Orto VG, Perrone S, Principi N, Esposito S. Biomarkers of Neonatal Sepsis: Where We Are and Where We Are Going. Antibiotics (Basel) 2023; 12:1233. [PMID: 37627653 PMCID: PMC10451659 DOI: 10.3390/antibiotics12081233] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 07/14/2023] [Accepted: 07/20/2023] [Indexed: 08/27/2023] Open
Abstract
Neonatal sepsis is a bacterial bloodstream infection leading to severe clinical manifestations frequently associated with death or irreversible long-term deficits. Antibiotics are the drug of choice to treat sepsis, regardless of age. In neonates, the lack of reliable criteria for a definite diagnosis and the supposition that an early antibiotic administration could reduce sepsis development in children at risk have led to a relevant antibiotic overuse for both prevention and therapy. The availability of biomarkers of neonatal sepsis that could alert the physician to an early diagnosis of neonatal sepsis could improve the short and long-term outcomes of true sepsis cases and reduce the indiscriminate and deleterious use of preventive antibiotics. The main aim of this narrative review is to summarize the main results in this regard and to detail the accuracy of currently used biomarkers for the early diagnosis of neonatal sepsis. Literature analysis showed that, despite intense research, the diagnosis of neonatal sepsis and the conduct of antibiotic therapy cannot be at present decided on the basis of a single biomarker. Given the importance of the problem and the need to reduce the abuse of antibiotics, further studies are urgently required. However, instead of looking for new biomarkers, it seems easier and more productive to test combinations of two or more of the presently available biomarkers. Moreover, studies based on omics technologies should be strongly boosted. However, while waiting for new information, the use of the clinical scores prepared by some scientific institutions could be suggested. Based on maternal risk factors and infant clinical indicators, sepsis risk can be calculated, and a significant reduction in antibiotic consumption can be obtained.
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Affiliation(s)
- Giovanni Boscarino
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy; (G.B.); (R.M.); (G.C.); (G.D.)
| | - Rossana Migliorino
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy; (G.B.); (R.M.); (G.C.); (G.D.)
| | - Giulia Carbone
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy; (G.B.); (R.M.); (G.C.); (G.D.)
| | - Giusy Davino
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy; (G.B.); (R.M.); (G.C.); (G.D.)
| | | | - Serafina Perrone
- Neonatal Unit, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy; (V.G.D.); (S.P.)
| | | | - Susanna Esposito
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy; (G.B.); (R.M.); (G.C.); (G.D.)
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14
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Zeng Z, Peng YZ, Yuan ZQ. [Research advances of sepsis biomarkers]. ZHONGHUA SHAO SHANG YU CHUANG MIAN XIU FU ZA ZHI 2023; 39:679-684. [PMID: 37805698 DOI: 10.3760/cma.j.cn501225-20230320-00086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Indexed: 10/09/2023]
Abstract
Sepsis is a life-threatening condition for patients. Biomarkers can be used for the diagnosis, treatment, and prognostic assessment of sepsis. In recent years, new biomarkers for sepsis have been discovered, and more than 250 biomarkers have been identified so far. The complexity of the sepsis process and the increased sensitivity of various detection techniques will lead to the emergence of new biomarkers. However, there is still a lack of specific diagnostic biomarkers and effective therapeutic approaches for sepsis in clinical practice. Therefore, the search for reliable biomarkers and the evaluation of the role of biomarkers in sepsis will undoubtedly aid in clinical decision-making. This article reviews the advances on research of sepsis biomarkers in order to improve understanding of current biomarkers of sepsis, and provide reference for the application of biomarkers in clinical diagnosis, treatment, and prognosis of sepsis.
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Affiliation(s)
- Z Zeng
- State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burn Research, the First Affiliated Hospital of Army Medical University (the Third Military Medical University), Chongqing 400038, China
| | - Y Z Peng
- State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burn Research, the First Affiliated Hospital of Army Medical University (the Third Military Medical University), Chongqing 400038, China
| | - Z Q Yuan
- State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burn Research, the First Affiliated Hospital of Army Medical University (the Third Military Medical University), Chongqing 400038, China
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15
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Maryam S, Krukiewicz K, Haq IU, Khan AA, Yahya G, Cavalu S. Interleukins (Cytokines) as Biomarkers in Colorectal Cancer: Progression, Detection, and Monitoring. J Clin Med 2023; 12:jcm12093127. [PMID: 37176567 PMCID: PMC10179696 DOI: 10.3390/jcm12093127] [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: 03/18/2023] [Revised: 04/18/2023] [Accepted: 04/20/2023] [Indexed: 05/15/2023] Open
Abstract
Cancer is the primary cause of death in economically developed countries and the second leading cause in developing countries. Colorectal cancer (CRC) is the third most common cause of cancer-related deaths worldwide. Risk factors for CRC include obesity, a diet low in fruits and vegetables, physical inactivity, and smoking. CRC has a poor prognosis, and there is a critical need for new diagnostic and prognostic biomarkers to reduce related deaths. Recently, studies have focused more on molecular testing to guide targeted treatments for CRC patients. The most crucial feature of activated immune cells is the production and release of growth factors and cytokines that modulate the inflammatory conditions in tumor tissues. The cytokine network is valuable for the prognosis and pathogenesis of colorectal cancer as they can aid in the cost-effective and non-invasive detection of cancer. A large number of interleukins (IL) released by the immune system at various stages of CRC can act as "biomarkers". They play diverse functions in colorectal cancer, and include IL-4, IL-6, IL-8, IL-11, IL-17A, IL-22, IL-23, IL-33, TNF, TGF-β, and vascular endothelial growth factor (VEGF), which are pro-tumorigenic genes. However, there are an inadequate number of studies in this area considering its correlation with cytokine profiles that are clinically useful in diagnosing cancer. A better understanding of cytokine levels to establish diagnostic pathways entails an understanding of cytokine interactions and the regulation of their various biochemical signaling pathways in healthy individuals. This review provides a comprehensive summary of some interleukins as immunological biomarkers of CRC.
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Affiliation(s)
- Sajida Maryam
- Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad 44000, Pakistan
| | - Katarzyna Krukiewicz
- Department of Physical Chemistry and Technology of Polymers, Silesian University of Technology, M. Strzody 9, 44-100 Gliwice, Poland
- Centre for Organic and Nanohybrid Electronics, Silesian University of Technology, Konarskiego 22B, 44-100 Gliwice, Poland
| | - Ihtisham Ul Haq
- Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad 44000, Pakistan
- Department of Physical Chemistry and Technology of Polymers, Silesian University of Technology, M. Strzody 9, 44-100 Gliwice, Poland
- Joint Doctoral School, Silesian University of Technology, Akademicka 2A, 44-100 Gliwice, Poland
| | - Awal Ayaz Khan
- Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad 44000, Pakistan
| | - Galal Yahya
- Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Al Sharqia, Egypt
- Department of Molecular Genetics, Faculty of Biology, Technical University of Kaiserslautern, Paul-Ehrlich Str. 24, 67663 Kaiserslautern, Germany
| | - Simona Cavalu
- Faculty of Medicine and Pharmacy, University of Oradea, P-ta 1 Decembrie 10, 410087 Oradea, Romania
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16
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A portable and low-cost centrifugal microfluidic platform for multiplexed colorimetric detection of protein biomarkers. Anal Chim Acta 2023; 1245:340823. [PMID: 36737129 DOI: 10.1016/j.aca.2023.340823] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 01/06/2023] [Accepted: 01/09/2023] [Indexed: 01/12/2023]
Abstract
Cytokines play a very important role in our immune system by acting as mediators to put up a coordinated defense against foreign elements in our body. Elevated levels of cytokines in the body can signal to an ongoing response of the immune system to some abnormality. Thus, the quantification of a panel of cytokines can provide valuable information regarding the diagnosis of specific diseases and state of overall health of an individual. Conventional Enzyme Linked Immunosorbent Assay (ELISA) is the gold-standard for quantification of cytokines, however the need for trained personnel and expensive equipment limits its application to centralized laboratories only. In this context, there is a lack of simple, low-cost and portable devices which can allow for quantification of panels of cytokines at point-of-care and/or resource limited settings. Here, we report the development of a versatile, low-cost and portable bead-based centrifugal microfluidic platform allowing for multiplexed detection of cytokines with minimal hands-on time and an integrated colorimetric signal readout without the need for any external equipment. As a model, multiplexed colorimetric quantification of three target cytokines i.e., Tumor necrosis factor alpha (TNF-α), Interferon gamma (IFN-γ) and Interleukin-2 (IL-2) was achieved in less than 30 min with limits of detection in ng/mL range. The developed platform was further evaluated using spiked-in plasma samples to test for matrix interference. The ease of use, low-cost and portability of the developed platform highlight its potential to serve as a sample-to-answer solution for detection of cytokine panels in resource limited settings.
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17
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Vásquez V, Orozco J. Detection of COVID-19-related biomarkers by electrochemical biosensors and potential for diagnosis, prognosis, and prediction of the course of the disease in the context of personalized medicine. Anal Bioanal Chem 2023; 415:1003-1031. [PMID: 35970970 PMCID: PMC9378265 DOI: 10.1007/s00216-022-04237-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 06/30/2022] [Accepted: 07/18/2022] [Indexed: 02/07/2023]
Abstract
As a more efficient and effective way to address disease diagnosis and intervention, cutting-edge technologies, devices, therapeutic approaches, and practices have emerged within the personalized medicine concept depending on the particular patient's biology and the molecular basis of the disease. Personalized medicine is expected to play a pivotal role in assessing disease risk or predicting response to treatment, understanding a person's health status, and, therefore, health care decision-making. This work discusses electrochemical biosensors for monitoring multiparametric biomarkers at different molecular levels and their potential to elucidate the health status of an individual in a personalized manner. In particular, and as an illustration, we discuss several aspects of the infection produced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a current health care concern worldwide. This includes SARS-CoV-2 structure, mechanism of infection, biomarkers, and electrochemical biosensors most commonly explored for diagnostics, prognostics, and potentially assessing the risk of complications in patients in the context of personalized medicine. Finally, some concluding remarks and perspectives hint at the use of electrochemical biosensors in the frame of other cutting-edge converging/emerging technologies toward the inauguration of a new paradigm of personalized medicine.
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Affiliation(s)
- Viviana Vásquez
- Max Planck Tandem Group in Nanobioengineering, Institute of Chemistry, Faculty of Natural and Exact Sciences, University of Antioquia, Complejo Ruta N, Calle 67 N° 52-20, Medellín, 050010, Colombia
| | - Jahir Orozco
- Max Planck Tandem Group in Nanobioengineering, Institute of Chemistry, Faculty of Natural and Exact Sciences, University of Antioquia, Complejo Ruta N, Calle 67 N° 52-20, Medellín, 050010, Colombia.
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18
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Yasmeen N, Selvaraj H, Lakhawat SS, Datta M, Sharma PK, Jain A, Khanna R, Srinivasan J, Kumar V. Possibility of averting cytokine storm in SARS-COV 2 patients using specialized pro-resolving lipid mediators. Biochem Pharmacol 2023; 209:115437. [PMID: 36731803 PMCID: PMC9884647 DOI: 10.1016/j.bcp.2023.115437] [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: 12/02/2022] [Revised: 01/23/2023] [Accepted: 01/24/2023] [Indexed: 01/31/2023]
Abstract
Fatal "cytokine storms (CS)" observed in critically ill COVID-19 patients are consequences of dysregulated host immune system and over-exuberant inflammatory response. Acute respiratory distress syndrome (ARDS), multi-system organ failure, and eventual death are distinctive symptoms, attributed to higher morbidity and mortality rates among these patients. Consequent efforts to save critical COVID-19 patients via the usage of several novel therapeutic options are put in force. Strategically, drugs being used in such patients are dexamethasone, remdesivir, hydroxychloroquine, etc. along with the approved vaccines. Moreover, it is certain that activation of the resolution process is important for the prevention of chronic diseases. Until recently Inflammation resolution was considered a passive process, rather it's an active biochemical process that can be achieved by the use of specialized pro-resolving mediators (SPMs). These endogenous mediators are an array of atypical lipid metabolites that include Resolvins, lipoxins, maresins, protectins, considered as immunoresolvents, but their role in COVID-19 is ambiguous. Recent evidence from studies such as the randomized clinical trial, in which omega 3 fatty acid was used as supplement to resolve inflammation in COVID-19, suggests that direct supplementation of SPMs or the use of synthetic SPM mimetics (which are still being explored) could enhance the process of resolution by regulating the aberrant inflammatory process and can be useful in pain relief and tissue remodeling. Here we discussed the biosynthesis of SPMs, & their mechanistic pathways contributing to inflammation resolution along with sequence of events leading to CS in COVID-19, with a focus on therapeutic potential of SPMs.
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Affiliation(s)
- Nusrath Yasmeen
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, Rajasthan, India
| | - Harikrishnan Selvaraj
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, Rajasthan, India
| | - Sudarshan S Lakhawat
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, Rajasthan, India
| | - Manali Datta
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, Rajasthan, India
| | - Pushpender K Sharma
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, Rajasthan, India
| | - Ajay Jain
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, Rajasthan, India
| | - Rakhi Khanna
- Rajasthan State Regional Forensic Science Laboratory, Kota, Rajasthan, India
| | | | - Vikram Kumar
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, Rajasthan, India.
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19
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Chikomba C, Dlamini S, George JA, Pillay T. COVID Diagnostics: From Molecules to Omics. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1412:141-158. [PMID: 37378765 DOI: 10.1007/978-3-031-28012-2_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/29/2023]
Abstract
The identification and genetic sequencing of a novel coronavirus was key to the diagnosis and management of the global pandemic. An understanding of the SARS-CoV-2 structure and mechanism of injury is vital to explaining the disease course and the pathophysiology of the signs and symptoms observed. This particularly as the presentation, disease course, and severity are noted to be highly variable. The role of the spike protein and angiotensin-converting enzyme 2 (ACE-2) receptor in immune response and viral entry provides great insight into current and future diagnostics and therapeutics. This article reviews the traditional diagnostic methods, which include molecular testing methods, antigen testing, and antibody testing. The gold standard for diagnosis of COVID-19 is reverse transcriptase polymerase chain reaction (RT-PCR). There have been multiple improvements to these principles to help optimize the sensitivity, specificity, and user friendliness of the method. In addition, advancements in gene sequencing and identification have been integral to identifying variants and managing outbreaks. Serological and immunological testing have made significant contributions to the management of the COVID-19 pandemic, each with its unique benefits and limitations. A growing role of the laboratory is in triaging patients to determine which patients will most benefit from hospitalization and specialized care. This is imperative for rationalizing resources during outbreaks. As we learn to live with the pandemic, novel testing methods include the use of multiomic technologies and the greater utility of point of care.
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Affiliation(s)
- Chemedzai Chikomba
- Department of Chemical Pathology. National Health Laboratory Services and University of Witwatersrand, Johannesburg, South Africa
| | - Siphelele Dlamini
- Department of Chemical Pathology. National Health Laboratory Services and University of Witwatersrand, Johannesburg, South Africa
| | - Jaya A George
- Wits Diagnostic and Innovation Hub, University of Witwatersrand, Johannesburg, South Africa.
| | - Taryn Pillay
- Department of Chemical Pathology. National Health Laboratory Services and University of Witwatersrand, Johannesburg, South Africa
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20
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Xue L, Guo R, Jin N, Wang S, Duan H, Qi W, Wang L, Zheng Y, Li Y, Lin J. Rapid and automatic Salmonella typhimurium detection integrating continuous-flow magnetic separation and dynamic impedance measurement. Food Control 2023. [DOI: 10.1016/j.foodcont.2022.109316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
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21
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Jamaludeen N, Lehmann J, Beyer C, Vogel K, Pierau M, Brunner-Weinzierl M, Spiliopoulou M. Assessment of Immune Status Using Inexpensive Cytokines: A Literature Review and Learning Approaches. SENSORS (BASEL, SWITZERLAND) 2022; 22:9785. [PMID: 36560154 PMCID: PMC9786078 DOI: 10.3390/s22249785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 11/22/2022] [Accepted: 12/05/2022] [Indexed: 06/17/2023]
Abstract
The emergence of point-of-care (POC) testing has lately been promoted to deliver rapid, reliable medical tests in critical life-threatening situations, especially in resource-limited settings. Recently, POC tests have witnessed further advances due to the technological revolution in smartphones. Smartphones are integrated as reliable readers to the POC results to improve their quantitative detection. This has enabled the use of more complex medical tests by the patient him/herself at home without the need for professional staff and sophisticated equipment. Cytokines, the important immune system biomarkers, are still measured today using the time-consuming Enzyme-Linked Immunosorbent Assay (ELISA), which can only be performed in specially equipped laboratories. Therefore, in this study, we investigate the current development of POC technologies suitable for the home testing of cytokines by conducting a PRISMA literature review. Then, we classify the collected technologies as inexpensive and expensive depending on whether the cytokines can be measured easily at home or not. Additionally, we propose a machine learning-based solution to even increase the efficiency of the cytokine measurement by leveraging the cytokines that can be inexpensively measured to predict the values of the expensive ones. In total, we identify 12 POCs for cytokine quantification. We find that Interleukin 1β (IL-1β), Interleukin 3 (IL-3), Interleukin 6 (IL-6), Interleukin 8 (IL-8) and Tumor necrosis factor (TNF) can be measured with inexpensive POC technology, namely at home. We build machine-learning models to predict the values of other expensive cytokines such as Interferon-gamma (IFN-γ), IL-10, IL-2, IL-17A, IL-17F, IL-4 and IL-5 by relying on the identified inexpensive ones in addition to the age of the individual. We evaluate to what extent the built machine learning models can use the inexpensive cytokines to predict the expensive ones on 351 healthy subjects from the public dataset 10k Immunomes. The models for IFN-γ show high results for the coefficient of determination: R2 = 0.743. The results for IL-5 and IL-4 are also promising, whereas the predictive model of IL-10 achieves only R2 = 0.126. Lastly, the results demonstrate the vital role of TNF and IL-6 in the immune system due to its high importance in the predictions of all the other expensive cytokines.
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Affiliation(s)
- Noor Jamaludeen
- Knowledge Management & Discovery Lab, Otto-von-Guericke University, 39106 Magdeburg, Germany
| | - Juliane Lehmann
- Knowledge Management & Discovery Lab, Otto-von-Guericke University, 39106 Magdeburg, Germany
| | - Christian Beyer
- Knowledge Management & Discovery Lab, Otto-von-Guericke University, 39106 Magdeburg, Germany
| | - Katrin Vogel
- Department of Experimental Pediatrics, University Hospital, Otto-von-Guericke University, 39120 Magdeburg, Germany
| | - Mandy Pierau
- Department of Experimental Pediatrics, University Hospital, Otto-von-Guericke University, 39120 Magdeburg, Germany
| | - Monika Brunner-Weinzierl
- Department of Experimental Pediatrics, University Hospital, Otto-von-Guericke University, 39120 Magdeburg, Germany
| | - Myra Spiliopoulou
- Knowledge Management & Discovery Lab, Otto-von-Guericke University, 39106 Magdeburg, Germany
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22
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Tremblay JA, Peron F, Kreitmann L, Textoris J, Brengel-Pesce K, Lukaszewicz AC, Quemeneur L, Vedrine C, Tan LK, Venet F, Rimmele T, Monneret G. A stratification strategy to predict secondary infection in critical illness-induced immune dysfunction: the REALIST score. Ann Intensive Care 2022; 12:76. [PMID: 35976460 PMCID: PMC9382015 DOI: 10.1186/s13613-022-01051-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 08/03/2022] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Although multiple individual immune parameters have been demonstrated to predict the occurrence of secondary infection after critical illness, significant questions remain with regards to the selection, timing and clinical utility of such immune monitoring tests. RESEARCH QUESTION As a sub-study of the REALISM study, the REALIST score was developed as a pragmatic approach to help clinicians better identify and stratify patients at high risk for secondary infection, using a simple set of relatively available and technically robust biomarkers. STUDY DESIGN AND METHODS This is a sub-study of a single-centre prospective cohort study of immune profiling in critically ill adults admitted after severe trauma, major surgery or sepsis/septic shock. For the REALIST score, five immune parameters were pre-emptively selected based on their clinical applicability and technical robustness. Predictive power of different parameters and combinations of parameters was assessed. The main outcome of interest was the occurrence of secondary infection within 30 days. RESULTS After excluding statistically redundant and poorly predictive parameters, three parameters remained in the REALIST score: mHLA-DR, percentage of immature (CD10- CD16-) neutrophils and serum IL-10 level. In the cohort of interest (n = 189), incidence of secondary infection at day 30 increased from 8% for patients with REALIST score of 0 to 46% in patients with a score of 3 abnormal parameters, measured ad D5-7. When adjusted for a priori identified clinical risk factors for secondary infection (SOFA score and invasive mechanical ventilation at D5-7), a higher REALIST score was independently associated with increased risk of secondary infection (42 events (22.2%), adjusted HR 3.22 (1.09-9.50), p = 0.034) and mortality (10 events (5.3%), p = 0.001). INTERPRETATION We derived and presented the REALIST score, a simple and pragmatic stratification strategy which provides clinicians with a clear assessment of the immune status of their patients. This new tool could help optimize care of these individuals and could contribute in designing future trials of immune stimulation strategies.
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Affiliation(s)
- Jan-Alexis Tremblay
- EA 7426 "Pathophysiology of Injury-Induced Immunosuppression" (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, Herriot Hospital, 5 place d'Arsonval, 69003, Lyon, France. .,Critical Care Service, Hôpital Maisonneuve-Rosemont, 5415 Boulevard de l'Assomption, Montréal, H1T2M4, Canada.
| | - Florian Peron
- EA 7426 "Pathophysiology of Injury-Induced Immunosuppression" (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, Herriot Hospital, 5 place d'Arsonval, 69003, Lyon, France
| | - Louis Kreitmann
- EA 7426 "Pathophysiology of Injury-Induced Immunosuppression" (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, Herriot Hospital, 5 place d'Arsonval, 69003, Lyon, France
| | - Julien Textoris
- EA 7426 "Pathophysiology of Injury-Induced Immunosuppression" (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, Herriot Hospital, 5 place d'Arsonval, 69003, Lyon, France
| | - Karen Brengel-Pesce
- EA 7426 "Pathophysiology of Injury-Induced Immunosuppression" (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, Herriot Hospital, 5 place d'Arsonval, 69003, Lyon, France
| | - Anne-Claire Lukaszewicz
- EA 7426 "Pathophysiology of Injury-Induced Immunosuppression" (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, Herriot Hospital, 5 place d'Arsonval, 69003, Lyon, France.,Anesthesia and Critical Care Medicine Department, Hospices Civils de Lyon, Edouard Herriot Hospital, 69437, Lyon, France
| | - Laurence Quemeneur
- Sanofi Pasteur, Sanofi 1541 avenue Marcel Mérieux, 69280, Marcy l'Etoile, France
| | | | - Lionel K Tan
- GSK, 980 Great West Road, Brentford, Middlesex, TW8 9GS, UK
| | - Fabienne Venet
- Immunology Laboratory, Hospices Civils de Lyon, Edouard Herriot Hospital, 69437, Lyon, France.,Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Team 'NLRP3 Inflammation and Immune Response to Sepsis', Université Claude Bernard-Lyon 1, Lyon, France
| | - Thomas Rimmele
- EA 7426 "Pathophysiology of Injury-Induced Immunosuppression" (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, Herriot Hospital, 5 place d'Arsonval, 69003, Lyon, France.,Anesthesia and Critical Care Medicine Department, Hospices Civils de Lyon, Edouard Herriot Hospital, 69437, Lyon, France
| | - Guillaume Monneret
- EA 7426 "Pathophysiology of Injury-Induced Immunosuppression" (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, Herriot Hospital, 5 place d'Arsonval, 69003, Lyon, France.,Immunology Laboratory, Hospices Civils de Lyon, Edouard Herriot Hospital, 69437, Lyon, France
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Ma XH, Liu JHZ, Liu CY, Sun WY, Duan WJ, Wang G, Kurihara H, He RR, Li YF, Chen Y, Shang H. ALOX15-launched PUFA-phospholipids peroxidation increases the susceptibility of ferroptosis in ischemia-induced myocardial damage. Signal Transduct Target Ther 2022; 7:288. [PMID: 35970840 PMCID: PMC9378747 DOI: 10.1038/s41392-022-01090-z] [Citation(s) in RCA: 122] [Impact Index Per Article: 40.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 06/02/2022] [Accepted: 06/26/2022] [Indexed: 12/31/2022] Open
Abstract
Myocardial ischemia/reperfusion (I/R) injury is a classic type of cardiovascular disease characterized by injury to cardiomyocytes leading to various forms of cell death. It is believed that irreversible myocardial damage resulted from I/R occurs due to oxidative stress evoked during the reperfusion phase. Here we demonstrate that ischemia triggers a specific redox reaction of polyunsaturated fatty acids (PUFA)-phospholipids in myocardial cells, which acts as a priming signaling that initiates the outbreak of robust oxidative damage in the reperfusion phase. Using animal and in vitro models, the crucial lipid species in I/R injury were identified to be oxidized PUFAs enriched phosphatidylethanolamines. Using multi-omics, arachidonic acid 15-lipoxygenase-1 (ALOX15) was identified as the primary mediator of ischemia-provoked phospholipid peroxidation, which was further confirmed using chemogenetic approaches. Collectively, our results reveal that ALOX15 induction in the ischemia phase acts as a “burning point” to ignite phospholipid oxidization into ferroptotic signals. This finding characterizes a novel molecular mechanism for myocardial ischemia injury and offers a potential therapeutic target for early intervention of I/R injury.
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Affiliation(s)
- Xiao-Hui Ma
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China.,Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, 510632, China.,International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China.,Institute of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi, 830054, China
| | - Jiang-Han-Zi Liu
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China.,Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, 510632, China.,International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China
| | - Chun-Yu Liu
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China.,Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, 510632, China.,International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China
| | - Wan-Yang Sun
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China.,Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, 510632, China.,International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China
| | - Wen-Jun Duan
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China.,Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, 510632, China.,International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China
| | - Guan Wang
- Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Hiroshi Kurihara
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China.,Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, 510632, China.,International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China
| | - Rong-Rong He
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China. .,Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, 510632, China. .,International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China.
| | - Yi-Fang Li
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China. .,Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, 510632, China. .,International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China.
| | - Yang Chen
- College of Pharmacy, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
| | - Hongcai Shang
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, 100700, Beijing, China.
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Frimpong A, Owusu EDA, Amponsah JA, Obeng-Aboagye E, van der Puije W, Frempong AF, Kusi KA, Ofori MF. Cytokines as Potential Biomarkers for Differential Diagnosis of Sepsis and Other Non-Septic Disease Conditions. Front Cell Infect Microbiol 2022; 12:901433. [PMID: 35811678 PMCID: PMC9260692 DOI: 10.3389/fcimb.2022.901433] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 05/16/2022] [Indexed: 01/08/2023] Open
Abstract
Sepsis defined as a dysregulated immune response is a major cause of morbidity in children. In sub-Saharan Africa, the clinical features of sepsis overlap with other frequent infections such as malaria, thus sepsis is usually misdiagnosed in the absence of confirmatory tests. Therefore, it becomes necessary to identify biomarkers that can be used to distinguish sepsis from other infectious diseases. We measured and compared the plasma levels of 18 cytokines (Th1 [GM-CSF, IFN-γ, TNF-α, IL-1β, 1L-2, IL-6, IL-8, IL-12/IL-23p40, IL-15], Th2[IL-4, IL-5, IL-13), Th17 [IL17A], Regulatory cytokine (IL-10) and 7 chemokines (MCP-1/CCL2, MIP-1α/CCL3, MIP-1β/CCL4, RANTES/CCL5, Eotaxin/CCL11, MIG/CXCL9 and IP-10/CXCL10 using the Human Cytokine Magnetic 25-Plex Panel in plasma samples obtained from children with sepsis, clinical malaria and other febrile conditions. Children with sepsis had significantly higher levels of IL-1β, IL-12 and IL-17A compared to febrile controls but lower levels of MIP1-β/CCL4, RANTES/CCL5 and IP10/CXCL10 when compared to children with malaria and febrile controls. Even though levels of most inflammatory responses were higher in malaria compared to sepsis, children with sepsis had a higher pro-inflammatory to anti-inflammatory ratio which seemed to be mediated by mostly monocytes. A principal component analysis and a receiver operator characteristic curve analysis, identified seven potential biomarkers; IL-1β, IL-7, IL-12, IL-1RA, RANTES/CCL5, MIP1β/CCL4 and IP10/CXCL10 that could discriminate children with sepsis from clinical malaria and other febrile conditions. The data suggests that sepsis is associated with a higher pro-inflammatory environment. These pro-inflammatory cytokines/chemokines could further be evaluated for their diagnostic potential to differentiate sepsis from malaria and other febrile conditions in areas burdened with infectious diseases.
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Affiliation(s)
- Augustina Frimpong
- Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana
- *Correspondence: Augustina Frimpong, ; Michael Fokuo Ofori,
| | - Ewurama D. A. Owusu
- Department of Medical Laboratory Sciences, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, Accra, Ghana
| | - Jones Amo Amponsah
- Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana
| | - Elizabeth Obeng-Aboagye
- Department of Medical Laboratory Sciences, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, Accra, Ghana
| | - William van der Puije
- Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana
| | - Abena Fremaah Frempong
- Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana
| | - Kwadwo Asamoah Kusi
- Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana
- Department of Biochemistry, Cell and Molecular Biology, College of Basic and Applied Sciences, University of Ghana, Accra, Ghana
| | - Michael Fokuo Ofori
- Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana
- Department of Biochemistry, Cell and Molecular Biology, College of Basic and Applied Sciences, University of Ghana, Accra, Ghana
- *Correspondence: Augustina Frimpong, ; Michael Fokuo Ofori,
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25
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An antifouling electrochemical aptasensor based on hyaluronic acid functionalized polydopamine for thrombin detection in human serum. Bioelectrochemistry 2022; 145:108073. [DOI: 10.1016/j.bioelechem.2022.108073] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 01/14/2022] [Accepted: 01/17/2022] [Indexed: 11/22/2022]
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26
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Yerrapragada R M, Mampallil D. Interferon-γ detection in point of care diagnostics: Short review. Talanta 2022; 245:123428. [PMID: 35427946 DOI: 10.1016/j.talanta.2022.123428] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 03/15/2022] [Accepted: 03/30/2022] [Indexed: 12/21/2022]
Abstract
Interferon (IFN)-γ is a cytokine secreted by immune cells. The elevated levels of IFN-γ are an early indicator of multiple diseases such as tuberculosis and autoimmune diseases. This short review focuses on different sensing methods based on optical, electrochemical, and mechanical principles. We explain how specific biorecognition molecules such as antibodies and aptamers are employed in the sensing methods. We also compare different surface functionalization methods and their details. Although the review gives an overview of only IFN-γ sensing, the same strategies can be applied to sensing other analytes with appropriate modifications.
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Affiliation(s)
- Manjoosha Yerrapragada R
- Indian Institute of Science Education and Research Tirupati, Mangalam P O, Tirupati, 517507, India.
| | - Dileep Mampallil
- Indian Institute of Science Education and Research Tirupati, Mangalam P O, Tirupati, 517507, India.
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27
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Lian K, Feng H, Liu S, Wang K, Liu Q, Deng L, Wang G, Chen Y, Liu G. Insulin quantification towards early diagnosis of prediabetes/diabetes. Biosens Bioelectron 2022; 203:114029. [DOI: 10.1016/j.bios.2022.114029] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 01/13/2022] [Accepted: 01/20/2022] [Indexed: 12/19/2022]
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28
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Rahbar M, Wu Y, Subramony JA, Liu G. Sensitive Colorimetric Detection of Interleukin-6 via Lateral Flow Assay Incorporated Silver Amplification Method. Front Bioeng Biotechnol 2021; 9:778269. [PMID: 34900966 PMCID: PMC8662996 DOI: 10.3389/fbioe.2021.778269] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 11/04/2021] [Indexed: 01/22/2023] Open
Abstract
Interleukin-6 (IL-6) is a pro/anti-inflammatory cytokine, the quantitative detection of which has been extensively considered for diagnosis of inflammatory associated diseases. However, there has not yet been a reliable, low-cost, and user-friendly platform developed for point-of-care (POC) detection of IL-6, which will eliminate the conventional costly, time-consuming, and complex assays. In this work, we developed a lateral flow assay for colorimetric detection of IL-6, using anti-IL-6 antibodies conjugated to gold nanoparticles (AuNPs) as the detection probes. Silver amplification technique was incorporated with the newly developed assay in order to enhance the obtained colorimetric signals, allowing sensitive detection of IL-6 in human serum in the desired physiological ranges (i.e., 5–1000 pg/mL). A limit of detection of 5 pg/mL could be achieved for IL-6 detection in serum with the amplification step which was not achievable in the standard assay. The corresponding specificity and reproducibility tests were all preformed to confirm the reliability of this assay for quantitative measurement of IL-6 in a POC manner.
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Affiliation(s)
- Mohammad Rahbar
- Graduate School of Biomedical Engineering, The University of New South Wales, Kensington, NSW, Australia
| | - Yuling Wu
- Integrated Bioanalysis, Clinical Pharmacology and Quantitative Pharmacology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States
| | - J Anand Subramony
- Biologics Engineering R&D, AstraZeneca, Gaithersburg, MD, United States
| | - Guozhen Liu
- Graduate School of Biomedical Engineering, The University of New South Wales, Kensington, NSW, Australia.,School of Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen, China
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29
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Jiang C, Fu Y, Liu G, Shu B, Davis J, Tofaris GK. Multiplexed Profiling of Extracellular Vesicles for Biomarker Development. NANO-MICRO LETTERS 2021; 14:3. [PMID: 34855021 PMCID: PMC8638654 DOI: 10.1007/s40820-021-00753-w] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Accepted: 10/22/2021] [Indexed: 05/09/2023]
Abstract
Extracellular vesicles (EVs) are cell-derived membranous particles that play a crucial role in molecular trafficking, intercellular transport and the egress of unwanted proteins. They have been implicated in many diseases including cancer and neurodegeneration. EVs are detected in all bodily fluids, and their protein and nucleic acid content offers a means of assessing the status of the cells from which they originated. As such, they provide opportunities in biomarker discovery for diagnosis, prognosis or the stratification of diseases as well as an objective monitoring of therapies. The simultaneous assaying of multiple EV-derived markers will be required for an impactful practical application, and multiplexing platforms have evolved with the potential to achieve this. Herein, we provide a comprehensive overview of the currently available multiplexing platforms for EV analysis, with a primary focus on miniaturized and integrated devices that offer potential step changes in analytical power, throughput and consistency.
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Affiliation(s)
- Cheng Jiang
- Nuffield Department of Clinical Neurosciences, New Biochemistry Building, University of Oxford, Oxford, OX1 3QU, UK.
- Department of Chemistry, University of Oxford, Oxford, OX1 3QZ, UK.
- Kavli Institute for Nanoscience Discovery, New Biochemistry Building, University of Oxford, Oxford, UK.
| | - Ying Fu
- Department of Chemistry, University of Oxford, Oxford, OX1 3QZ, UK
| | - Guozhen Liu
- School of Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen, 518172, People's Republic of China
| | - Bowen Shu
- Dermatology Hospital, Southern Medical University, Guangzhou, 510091, People's Republic of China
| | - Jason Davis
- Department of Chemistry, University of Oxford, Oxford, OX1 3QZ, UK.
| | - George K Tofaris
- Nuffield Department of Clinical Neurosciences, New Biochemistry Building, University of Oxford, Oxford, OX1 3QU, UK.
- Kavli Institute for Nanoscience Discovery, New Biochemistry Building, University of Oxford, Oxford, UK.
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30
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Lohcharoenkal W, Abbas Z, Rojanasakul Y. Advances in Nanotechnology-Based Biosensing of Immunoregulatory Cytokines. BIOSENSORS 2021; 11:364. [PMID: 34677320 PMCID: PMC8533878 DOI: 10.3390/bios11100364] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/22/2021] [Accepted: 09/26/2021] [Indexed: 12/13/2022]
Abstract
Cytokines are a large group of small proteins secreted by immune and non-immune cells in response to external stimuli. Much attention has been given to the application of cytokines' detection in early disease diagnosis/monitoring and therapeutic response assessment. To date, a wide range of assays are available for cytokines detection. However, in specific applications, multiplexed or continuous measurements of cytokines with wearable biosensing devices are highly desirable. For such efforts, various nanomaterials have been extensively investigated due to their extraordinary properties, such as high surface area and controllable particle size and shape, which leads to their tunable optical emission, electrical, and magnetic properties. Different types of nanomaterials such as noble metal, metal oxide, and carbon nanoparticles have been explored for various biosensing applications. Advances in nanomaterial synthesis and device development have led to significant progress in pushing the limit of cytokine detection. This article reviews currently used methods for cytokines detection and new nanotechnology-based biosensors for ultrasensitive cytokine detection.
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Affiliation(s)
| | - Zareen Abbas
- Department of Chemistry and Molecular Biology, University of Gothenburg, Kemigården 4, SE-412 96 Gothenburg, Sweden
| | - Yon Rojanasakul
- Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26505, USA
- West Virginia University Cancer Institute, West Virginia University, Morgantown, WV 26505, USA
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31
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Johnston L, Wang G, Hu K, Qian C, Liu G. Advances in Biosensors for Continuous Glucose Monitoring Towards Wearables. Front Bioeng Biotechnol 2021; 9:733810. [PMID: 34490230 PMCID: PMC8416677 DOI: 10.3389/fbioe.2021.733810] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 08/09/2021] [Indexed: 11/18/2022] Open
Abstract
Continuous glucose monitors (CGMs) for the non-invasive monitoring of diabetes are constantly being developed and improved. Although there are multiple biosensing platforms for monitoring glucose available on the market, there is still a strong need to enhance their precision, repeatability, wearability, and accessibility to end-users. Biosensing technologies are being increasingly explored that use different bodily fluids such as sweat and tear fluid, etc., that can be calibrated to and therefore used to measure blood glucose concentrations accurately. To improve the wearability of these devices, exploring different fluids as testing mediums is essential and opens the door to various implants and wearables that in turn have the potential to be less inhibiting to the wearer. Recent developments have surfaced in the form of contact lenses or mouthguards for instance. Challenges still present themselves in the form of sensitivity, especially at very high or low glucose concentrations, which is critical for a diabetic person to monitor. This review summarises advances in wearable glucose biosensors over the past 5 years, comparing the different types as well as the fluid they use to detect glucose, including the CGMs currently available on the market. Perspectives on the development of wearables for glucose biosensing are discussed.
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Affiliation(s)
- Lucy Johnston
- School of Engineering, The University of Glasgow, Glasgow, United Kingdom
| | - Gonglei Wang
- School of Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen, China
| | - Kunhui Hu
- Shenzhen YHLO Biotech Co., Ltd., Shenzhen, China
| | - Chungen Qian
- The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics, Hubei Bioinformatics and Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Guozhen Liu
- School of Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen, China
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