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Du N, Xiao Y, Li YG, Li CY, Li YL, Chen J, Li X, Li Y, Zhou YL, Luo LS, Wang P. The role of cytokines in predicting the therapeutic effect of non-suicidal self-injury in adolescents: a longitudinal study. BMC Psychiatry 2025; 25:225. [PMID: 40069634 PMCID: PMC11900266 DOI: 10.1186/s12888-025-06650-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Accepted: 02/21/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Neuroinflammatory processes are directly involved in the pathogenesis of non-suicidal self-injury (NSSI) among adolescents. However, their role in predicting the outcome of adolescent NSSI is unknown. This study aimed to explore the relationship between inflammatory cytokines and their effect on NSSI treatment through a prospective investigation. METHODS Thirty-two healthy adolescents and 199 adolescents who had engaged in NSSI were recruited. Blood samples were obtained from all participants to determine the concentration of inflammatory cytokines at enrollment. Thereafter, the NSSI group completed surveys on their NSSI behaviors after 3, 6, and 12 months. The outcomes of their NSSI behaviors were evaluated using the indexes of NSSI number and NSSI impulsivity. RESULTS The results showed that the mean NSSI number and NSSI impulsivity of the participants both showed a decline tendency over time. However, regarding the NSSI number, the significant treatment effect only emerged after 6 months. The abnormal rates of IL-1βand IL-8 levels of the NSSI group were significantly higher than those of healthy controls (χ2 = 3.945, 27.394; P < 0.05). In the regression models, high IL-8 level (β: 0.225, 95% CI: 0.001, 0.005; p = 0.001), high TNF-α level (β: 0.157, 95% CI: 0.023, 0.244; p = 0.018), and low IL-10 level (β: - 0.261, 95% CI: - 2.678, - 0.901; p = 0.017) could predict the treatment effect of NSSI number. High level of IL-8 (β: 0.233, 95% CI: 0.002, 0.009; p = 0.001) and long duration of medical treatment (β: 0.285, 95% CI: 0.234, 0.649; p < 0.001) could predict the treatment effect of NSSI impulsivity. When considering the two indexes together, the role of screened-out cytokines, IL-8 (OR = 1.065, 95% CI: 1.032,1.099; p < 0.001), TNF-α (OR = 1.839, 95% CI: 1.063, 3.182; p = 0.029) and IL-10 (OR = 0.031, 95% CI: 0.002, 0.541; p = 0.017), were still stable. CONCLUSIONS Employing the assessment of inflammatory cytokines among adolescents who engage in NSSI may be helpful in predicting their treatment outcome and designing other suitable treatment schemes in advance. TRIAL REGISTRATION registered in https://www.medicalresearch.org.cn/ . Retrospectively registered: registered in https://www.chictr.org.cn/ . REGISTRATION NUMBER ChiCTR2500097375. Date of registration: 18th February, 2025.
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Affiliation(s)
- Na Du
- Psychosomatic Medical Center, The Fourth People's Hospital of Chengdu, City Chengdu, Sichuan province, China.
- MOE Key Lab for Neuroinformation, The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China, Sichuan province, City Chengdu, China.
| | - Yu Xiao
- Psychosomatic Medical Center, The Fourth People's Hospital of Chengdu, City Chengdu, Sichuan province, China
| | - Yun-Ge Li
- Psychosomatic Medical Center, The Fourth People's Hospital of Chengdu, City Chengdu, Sichuan province, China
| | - Chun-Ya Li
- Psychosomatic Medical Center, The Fourth People's Hospital of Chengdu, City Chengdu, Sichuan province, China
| | - Ya-Lan Li
- Psychosomatic Medical Center, The Fourth People's Hospital of Chengdu, City Chengdu, Sichuan province, China
| | - Jia Chen
- Psychosomatic Medical Center, The Fourth People's Hospital of Chengdu, City Chengdu, Sichuan province, China
| | - Xin Li
- School of Medicine, Chengdu Women's and Children's Central Hospital, University of Electronic Science and Technology of China, City Chengdu, Sichuan province, China
| | - Yao Li
- Psychosomatic Medical Center, The Fourth People's Hospital of Chengdu, City Chengdu, Sichuan province, China
| | - Ya-Ling Zhou
- Psychosomatic Medical Center, The Fourth People's Hospital of Chengdu, City Chengdu, Sichuan province, China
| | - Li-Shi Luo
- Psychosomatic Medical Center, The Fourth People's Hospital of Chengdu, City Chengdu, Sichuan province, China
| | - Ping Wang
- Psychosomatic Medical Center, The Fourth People's Hospital of Chengdu, City Chengdu, Sichuan province, China
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Leung CY, Weiss SJ. Cytokines and Depressive Symptoms Among Adolescents. Biol Res Nurs 2025:10998004251318385. [PMID: 39902492 DOI: 10.1177/10998004251318385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2025]
Abstract
Background: Inflammation has been linked to an increased risk of depression, but there is limited and conflicting research on the role of inflammatory markers in adolescent depression. The purpose of this study was to examine associations between cytokines TNF-α, IL-1β, IL-6, and IL-8 and depression among a community-based sample of adolescents (13-19 years of age). Methods: Salivary samples were self-collected by adolescents for assay of cytokines. The Patient Health Questionnaire-9 (PHQ-9) was used to measure depressive symptoms and clinical depression, where a score ≥11 indicated the threshold for experiencing clinical depression. Multiple linear and logistic regression models were used to examine the relationships between cytokines and depression, adjusting for age, sex, ethnicity, income, and body mass index. Results: The mean age of the 83 participants was 15.86 years. Eight participants screened positive for depression; the mean depressive symptom score was 5.11. Higher levels of IL-6 (Coef = 1.33, p < .001) and IL-8 (Coef = 0.69, p = .025) were associated with more frequent depressive symptoms while higher levels of TNF-α (OR = 2.50, p = .002), IL-1β (OR = 1.98, p = .001), and IL-8 (OR = 2.44, p = .008) were associated with greater odds of meeting criteria for clinical depression. Conclusions: Future research should focus on factors that induce higher cytokine levels and the mechanisms underlying their effects on depression. Cytokines assessed in this study may ultimately have implications as methods for depression screening or targets for biologic interventions to prevent and treat adolescent depression.
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Affiliation(s)
- Cherry Y Leung
- Department of Community Health Systems, School of Nursing, University of California San Francisco, San Francisco, CA, USA
| | - Sandra J Weiss
- Department of Community Health Systems, School of Nursing, University of California San Francisco, San Francisco, CA, USA
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Righi D, Manco C, Pardini M, Stufano A, Schino V, Pelagotti V, Massa F, Stefano ND, Plantone D. Investigating interleukin-8 in Alzheimer's disease: A comprehensive review. J Alzheimers Dis 2025; 103:38-55. [PMID: 39558604 DOI: 10.1177/13872877241298973] [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: 11/20/2024]
Abstract
Several studies indicate that the development of Alzheimer's disease (AD) has strong interactions with immune mechanisms within the brain, indicating a close association between inflammation in the central nervous system and the progression of neurodegeneration. Despite considerable progress in understanding the inflammatory aspects of AD, several of them remain unresolved. Pro-inflammatory cytokines and microglia are pivotal components in the inflammatory cascade. Among these, the role of interleukin-8 (IL-8) in neurodegeneration seems complex and multifaceted, involving inflammation, neurotoxicity, blood-brain barrier disruption, and oxidative stress, and is still poorly characterized. We conducted a review to describe the evidence of IL-8 involvement in AD. IL-8 is a cytokine known for its proinflammatory properties and typically produced by macrophages, predominantly functions as a chemotactic signal for attracting neutrophils to inflamed sites in the bloodstream. Interestingly, IL-8 is also present in the brain, where it is primarily released by microglia in response to inflammatory signals. This review aims to provide a comprehensive overview of the structure, function, and regulatory mechanisms of IL-8 relevant to AD pathology.
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Affiliation(s)
- Delia Righi
- Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
| | - Carlo Manco
- Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
| | - Matteo Pardini
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova, Italy
| | - Angela Stufano
- Department of Interdisciplinary Medicine, University of Bari Aldo Moro, Bari, Italy
| | - Valentina Schino
- Department of Interdisciplinary Medicine, University of Bari Aldo Moro, Bari, Italy
| | - Virginia Pelagotti
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova, Italy
| | - Federico Massa
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova, Italy
| | - Nicola De Stefano
- Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
| | - Domenico Plantone
- Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
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O'Hora KP, Amir CM, Chiem E, Schleifer CH, Grigoryan V, Kushan-Wells L, Chiang JJ, Cole S, Irwin MR, Bearden CE. Differential inflammatory profiles in carriers of reciprocal 22q11.2 copy number variants. Psychoneuroendocrinology 2024; 169:107135. [PMID: 39116521 DOI: 10.1016/j.psyneuen.2024.107135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 07/10/2024] [Accepted: 07/12/2024] [Indexed: 08/10/2024]
Abstract
BACKGROUND Genetic copy number variants (CNVs; i.e., a deletion or duplication) at the 22q11.2 locus confer increased risk of neuropsychiatric disorders and immune dysfunction. Inflammatory profiles of 22q11.2 CNV carriers can shed light on gene-immune relationships that may be related to neuropsychiatric symptoms. However, little is known about inflammation and its relationship to clinical phenotypes in 22q11.2 CNV carriers. Here, we investigate differences in peripheral inflammatory markers in 22q11.2 CNV carriers and explore their relationship with psychosis risk symptoms and sleep disturbance. METHODS Blood samples and clinical assessments were collected from 22q11.2 deletion (22qDel) carriers (n=45), 22q11.2 duplication (22qDup) carriers (n=29), and typically developing (TD) control participants (n=92). Blood plasma levels of pro-inflammatory cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), and anti-inflammatory cytokine interleukin-10 (IL-10) were measured using a MesoScale Discovery multiplex immunoassay. Plasma levels of C-reactive protein (CRP) were measured using Enzyme-linked Immunosorbent Assay (ELISA). Linear mixed effects models controlling for age, sex, and body mass index were used to: a) examine group differences in inflammatory markers between 22qDel, 22qDup, and TD controls, b) test differences in inflammatory markers between 22qDel carriers with psychosis risk symptoms (22qDelPS+) and those without (22qDelPS-), and c) conduct an exploratory analysis testing the effect of sleep disturbance on inflammation in 22qDel and 22qDup carriers. A false discovery rate correction was used to correct for multiple comparisons. RESULTS 22qDup carriers exhibited significantly elevated levels of IL-8 relative to TD controls (q<0.001) and marginally elevated IL-8 levels relative to 22qDel carriers (q=0.08). There were no other significant differences in inflammatory markers between the three groups (q>0.13). 22qDelPS+ exhibited increased levels of IL-8 relative to both 22qDelPS- (q=0.02) and TD controls (p=0.002). There were no relationships between sleep and inflammatory markers that survived FDR correction (q>0.14). CONCLUSION Our results suggest that CNVs at the 22q11.2 locus may have differential effects on inflammatory processes related to IL-8, a key mediator of inflammation produced by macrophages and microglia. Further, these IL-8-mediated inflammatory processes may be related to psychosis risk symptoms in 22qDel carriers. Additional research is required to understand the mechanisms contributing to these differential levels of IL-8 between 22q11.2 CNV carriers and IL-8's association with psychosis risk.
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Affiliation(s)
- Kathleen P O'Hora
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA; Neuroscience Interdepartmental Program, University of California Los Angeles, Los Angeles, CA, USA
| | - Carolyn M Amir
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA
| | - Emily Chiem
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA; Molecular, Cellular, and Integrative Physiology Program, University of California Los Angeles, Los Angeles, CA, USA
| | - Charles H Schleifer
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA; Neuroscience Interdepartmental Program, University of California Los Angeles, Los Angeles, CA, USA
| | - Vardui Grigoryan
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA
| | - Leila Kushan-Wells
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA
| | | | - Steven Cole
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA; Norman Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA
| | - Michael R Irwin
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA; Norman Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA
| | - Carrie E Bearden
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA; Department of Psychology, University of California, Los Angeles, CA, USA.
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Wang S, Kawashima N, Han P, Sunada-Nara K, Yu Z, Tazawa K, Fujii M, Kieu TQ, Okiji T. MicroRNA-27a-5p Downregulates Expression of Proinflammatory Cytokines in Lipopolysaccharide-Stimulated Human Dental Pulp Cells via the NF-κB Signaling Pathway. Int J Mol Sci 2024; 25:9694. [PMID: 39273640 PMCID: PMC11395329 DOI: 10.3390/ijms25179694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 09/05/2024] [Accepted: 09/05/2024] [Indexed: 09/15/2024] Open
Abstract
MicroRNA-27a-5p (miR-27a-5p) was significantly upregulated in dental pulp inflammation, yet its underlying mechanisms remain unclear. This study investigated the effect of miR-27a-5p on the expression of proinflammatory cytokines in human dental pulp cells (hDPCs) stimulated by lipopolysaccharide (LPS). LPS-stimulated hDPCs showed concurrent increases in the expression of miR-27a-5p and proinflammatory cytokines (IL-6, IL-8, and MCP1), and the increased expression was suppressed by NF-κB inhibitor BAY 11-0785. Transfection of the miR-27a-5p mimic downregulated the expression of proinflammatory cytokines, NF-κB activity, and the expression of NF-κB signaling activators (TAB1, IRAK4, RELA, and FSTL1) in LPS-stimulated hDPCs. Luciferase reporter assays revealed that miR-27a-5p bound directly to the 3'-UTR of TAB1. siTAB1 downregulated NF-κB activity and proinflammatory cytokine expression. Downregulation of proinflammatory cytokine expression, NF-κB activity, and NF-κB signaling activator expression (TAB1, IRAK4, and RELA) was also found in LPS-stimulated rat incisor pulp tissue explants following transfection with the miR-27a-5p mimic ex vivo. MiR-27a-5p, whose expression was induced by NF-κB signaling, negatively regulated the synthesis of proinflammatory cytokines via targeting NF-κB signaling. In particular, TAB1, a potent NF-κB activator, was targeted by miR-27a-5p. These results provide insights into the negative regulatory effects of miR-27a-5p, particularly those targeting the TAB1-NF-κB signaling pathway, on pulp inflammation.
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Affiliation(s)
- Shihan Wang
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan
| | - Nobuyuki Kawashima
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan
| | - Peifeng Han
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan
| | - Keisuke Sunada-Nara
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan
| | - Ziniu Yu
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan
| | - Kento Tazawa
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan
| | - Mayuko Fujii
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan
| | - Thoai Quoc Kieu
- Department of Pediatric Dentistry, Faculty of Odonto-Stomatology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 17000, Vietnam
| | - Takashi Okiji
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan
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Nawal RR, Yadav S, Duncan HF, Talwar S, Kaushik A, Singh VK, Koner BC. Discriminatory performance of the pulpal inflammatory biomarkers; Interleukin-8 and TNF-α in patients with symptoms indicative of reversible and irreversible pulpitis: A diagnostic accuracy study. Int Endod J 2024; 57:1200-1211. [PMID: 38703070 DOI: 10.1111/iej.14078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 04/03/2024] [Accepted: 04/21/2024] [Indexed: 05/06/2024]
Abstract
AIM The success of vital pulp treatment (VPT) procedures is dependent on an accurate diagnosis of the pulpal inflammatory condition. Compared with current subjective pulpal diagnostic tests, inflammatory molecular biomarkers involved in the pathogenesis of pulpitis represent potential objective indicators of the degree of pulpal inflammation. Therefore, the aim of this study was to quantify level of inflammatory biomarkers - Interleukin 8 (IL-8) and TNF-α in patients diagnosed with reversible pulpitis (RP), irreversible pulpitis (IR) and normal pulp (NP) and investigate their diagnostic accuracy in differentiating between healthy and inflamed conditions. METHODOLOGY This prospective, cross-sectional study enrolled 72 patients aged 14-53 years with extremely deep carious lesions after establishing a clinical diagnosis of RP (n = 42), symptomatic IR (n = 22) and NP (n = 8). 50 μL of pulpal blood sample was collected from all the patients using a micropipette after pulpal exposure. The level of IL-8 and TNF-α was assessed in pg/mL using enzyme-linked immunosorbent assays. Mann-Whitney U test was applied to establish the association between IL-8/TNF-α level and degree of pulp inflammation. Receiver operating curve (ROC) analysis was carried out to calculate area under the curve (AUC) for RP versus IR. Cut-off values were established using Youden's index. RESULTS IL-8 and TNF-α levels differed significantly between RP and IR groups (p ≤ .001). The median value of IL-8 in RP and IP groups was 259.8 pg/mL [187.5-310.0] and 1357.8 pg/mL [1036.7-2177.6] respectively. The AUC-ROC curve for RP versus IR was 0.997 with 95.5% sensitivity and 99.76% specificity. The median value of TNF-α in RP and IR groups was 75.4 pg/mL [62.7-95.8] and 157.6 pg/mL [94.1-347.3]. The AUC-ROC curve for TNF-α was 0.812 with a sensitivity and specificity of 59.1% and 92.1%, respectively. IL-8 and TNF-α levels were below detection levels for all NP samples. CONCLUSION This study showed that pulpal blood could provide an excellent medium for establishing pulpal diagnosis under extremely deep carious lesions. The selected cytokines, IL-8 and TNF-α, demonstrated excellent discriminatory performance for reversible and irreversible pulpitis. Future studies should correlate the IL-8/TNF-α levels with VPT treatment outcomes.
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Affiliation(s)
- Ruchika Roongta Nawal
- Department of Conservative Dentistry & Endodontics, Maulana Azad Institute of Dental Sciences, New Delhi, India
| | - Sudha Yadav
- Department of Conservative Dentistry & Endodontics, Maulana Azad Institute of Dental Sciences, New Delhi, India
| | - Henry Fergus Duncan
- Division of Restorative Dentistry, Dublin Dental University Hospital, Trinity College Dublin, Dublin, Ireland
| | - Sangeeta Talwar
- Department of Conservative Dentistry & Endodontics, Maulana Azad Institute of Dental Sciences, New Delhi, India
| | - Aishvarya Kaushik
- Department of Conservative Dentistry & Endodontics, Maulana Azad Institute of Dental Sciences, New Delhi, India
| | - Vijay K Singh
- Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi, India
| | - Bidhan C Koner
- Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi, India
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Liu Y, Chen L. Impact of interleukin 6 levels on acute lung injury risk and disease severity in critically ill sepsis patients. World J Clin Cases 2024; 12:5374-5381. [PMID: 39156085 PMCID: PMC11238679 DOI: 10.12998/wjcc.v12.i23.5374] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 05/16/2024] [Accepted: 06/04/2024] [Indexed: 07/05/2024] Open
Abstract
BACKGROUND Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury (ALI) and multiple organ dysfunction syndrome (MODS). Interleukin 6 (IL-6) is a pro-inflammatory cytokine that plays a crucial role in the pathogenesis of sepsis and its complications. AIM To investigate the relationship among plasma IL-6 levels, risk of ALI, and disease severity in critically ill patients with sepsis. METHODS This prospective and observational study was conducted in the intensive care unit of a tertiary care hospital between January 2021 and December 2022. A total of 83 septic patients were enrolled. Plasma IL-6 levels were measured upon admission using an enzyme-linked immunosorbent assay. The development of ALI and MODS was monitored during hospitalization. Disease severity was evaluated by Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores. RESULTS Among the 83 patients with sepsis, 38 (45.8%) developed ALI and 29 (34.9%) developed MODS. Plasma IL-6 levels were significantly higher in patients who developed ALI than in those without ALI (median: 125.6 pg/mL vs 48.3 pg/mL; P < 0.001). Similarly, patients with MODS had higher IL-6 levels than those without MODS (median: 142.9 pg/mL vs 58.7 pg/mL; P < 0.001). Plasma IL-6 levels were strongly and positively correlated with APACHE II (r = 0.72; P < 0.001) and SOFA scores (r = 0.68; P < 0.001). CONCLUSION Elevated plasma IL-6 levels in critically ill patients with sepsis were associated with an increased risk of ALI and MODS. Higher IL-6 levels were correlated with greater disease severity, as reflected by higher APACHE II and SOFA scores. These findings suggest that IL-6 may serve as a biomarker for predicting the development of ALI and disease severity in patients with sepsis.
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Affiliation(s)
- Ya Liu
- Department of Intensive Care Unit, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 201900, China
| | - Li Chen
- Department of Intensive Care Unit, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 201900, China
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Li Z, Tian J, Yang F. Tyrosine nitration enhances the allergenic potential of house dust mite allergen Der p 2. ENVIRONMENTAL RESEARCH 2024; 252:118826. [PMID: 38579999 DOI: 10.1016/j.envres.2024.118826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 03/27/2024] [Accepted: 03/28/2024] [Indexed: 04/07/2024]
Abstract
Nitration of allergenic proteins caused by atmospheric pollutants O3 and NO2 may enhance their allergenic potential. In the study, the influence of nitration was investigated on the allergenicity of Der p 2, which is a main allergen from house dust mites and plays an important role in allergenic rhinitis and asthma. The results reveal that nitrated Der p 2 enhanced the IgE-binding capacity, upregulated the mRNA expression and release of IL-6 and IL-8 from bronchial epithelial cells, and induced higher levels of specific-IgE, TH2 cytokines and white blood cells in mice. Besides, nitrated Der p 2 caused more severe oxidative stress and allergenic symptoms in mice. It is concluded that nitration enhanced the allergenicity of Der p 2 through not only directly inducing higher amount of specific-IgE and stronger responses of TH2 cytokines, but also indirectly aggravating allergic symptoms by oxidative stress and adjuvant-like activation airway epithelial cells. The study suggests that the contribution of nitration to the promotion in allergenicity should not be ignored when precisely assessing the risk of house dust mite allergens in real environment.
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Affiliation(s)
- Zhiqi Li
- Key Laboratory of Environment Remediation and Ecological Health, Ministry of Education, College of Natural Resources and Environmental Science, Zhejiang University, 310058, Hangzhou, China
| | - Jingyi Tian
- Key Laboratory of Environment Remediation and Ecological Health, Ministry of Education, College of Natural Resources and Environmental Science, Zhejiang University, 310058, Hangzhou, China
| | - Fangxing Yang
- Key Laboratory of Environment Remediation and Ecological Health, Ministry of Education, College of Natural Resources and Environmental Science, Zhejiang University, 310058, Hangzhou, China; Innovation Center of Yangtze River Delta, Zhejiang University, 314100, Jiashan, China.
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9
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Hernández-Sarmiento LJ, Valdés-López JF, Urcuqui-Inchima S. Zika virus infection suppresses CYP24A1 and CAMP expression in human monocytes. Arch Virol 2024; 169:135. [PMID: 38839691 PMCID: PMC11153301 DOI: 10.1007/s00705-024-06050-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 03/27/2024] [Indexed: 06/07/2024]
Abstract
Monocytes are the primary targets of Zika virus (ZIKV) and are associated with ZIKV pathogenesis. Currently, there is no effective treatment for ZIKV infection. It is known that 1,25-dihydroxy vitamin D3 (VitD3) has strong antiviral activity in dengue virus-infected macrophages, but it is unknown whether VitD3 inhibits ZIKV infection in monocytes. We investigated the relationship between ZIKV infection and the expression of genes of the VitD3 pathway, as well as the inflammatory response of infected monocytes in vitro. ZIKV replication was evaluated using a plaque assay, and VitD3 pathway gene expression was analyzed by RT-qPCR. Pro-inflammatory cytokines/chemokines were quantified using ELISA. We found that VitD3 did not suppress ZIKV replication. The results showed a significant decrease in the expression of vitamin D3 receptor (VDR), cytochrome P450 family 24 subfamily A member 1 (CYP24A1), and cathelicidin antimicrobial peptide (CAMP) genes upon ZIKV infection. Treatment with VitD3 was unable to down-modulate production of pro-inflammatory cytokines, except TNF-α, and chemokines. This suggests that ZIKV infection inhibits the expression of VitD3 pathway genes, thereby preventing VitD3-dependent inhibition of viral replication and the inflammatory response. This is the first study to examine the effects of VitD3 in the context of ZIKV infection, and it has important implications for the role of VitD3 in the control of viral replication and inflammatory responses during monocyte infection.
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Affiliation(s)
| | - Juan Felipe Valdés-López
- Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia
| | - Silvio Urcuqui-Inchima
- Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.
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Shkundin A, Halaris A. IL-8 (CXCL8) Correlations with Psychoneuroimmunological Processes and Neuropsychiatric Conditions. J Pers Med 2024; 14:488. [PMID: 38793070 PMCID: PMC11122344 DOI: 10.3390/jpm14050488] [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: 03/18/2024] [Revised: 04/26/2024] [Accepted: 04/30/2024] [Indexed: 05/26/2024] Open
Abstract
Interleukin-8 (IL-8/CXCL8), an essential CXC chemokine, significantly influences psychoneuroimmunological processes and affects neurological and psychiatric health. It exerts a profound effect on immune cell activation and brain function, suggesting potential roles in both neuroprotection and neuroinflammation. IL-8 production is stimulated by several factors, including reactive oxygen species (ROS) known to promote inflammation and disease progression. Additionally, CXCL8 gene polymorphisms can alter IL-8 production, leading to potential differences in disease susceptibility, progression, and severity across populations. IL-8 levels vary among neuropsychiatric conditions, demonstrating sensitivity to psychosocial stressors and disease severity. IL-8 can be detected in blood circulation, cerebrospinal fluid (CSF), and urine, making it a promising candidate for a broad-spectrum biomarker. This review highlights the need for further research on the diverse effects of IL-8 and the associated implications for personalized medicine. A thorough understanding of its complex role could lead to the development of more effective and personalized treatment strategies for neuropsychiatric conditions.
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Affiliation(s)
| | - Angelos Halaris
- Department of Psychiatry and Behavioral Neurosciences, Loyola University Chicago Stritch School of Medicine, Loyola University Medical Center, Maywood, IL 60153, USA;
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11
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Lima AF, Oliveira AAD, Fronza BM, Braga RR, Andia DC. Toxicity and cytokine release from human dental pulp stem cells after exposure to universal dental adhesives cured by single peak and polywave LEDs. Dent Mater 2024; 40:837-841. [PMID: 38570242 DOI: 10.1016/j.dental.2024.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 03/21/2024] [Indexed: 04/05/2024]
Abstract
OBJECTIVES to assess the impact of universal adhesives, cured with single-peak and polywave LEDs, on the metabolic activity and cytokine release of human dental pulp stem cells (hDPSCs). In addition, analyze the degree of conversion (DC) of the adhesives cured with the different LEDs. METHODS Discs (5 mm diameter, 1 mm thick) were prepared using three universal adhesives: Single Bond Universal (SBU, 3 M ESPE), Optibond Universal (OBU, Kerr), and Zipbond Universal (ZBU, SDI). These discs were cured for 40 s using a single-peak (DeepCure, 3 M ESPE) or a polywave light-emmiting diode (LED) curing unit (Valo Grand, Ultradent). After 24 h, the specimens were placed in 24-well culture plates, each containing 1 mL of culture medium for 24 h. hDPSCs (1.8 ×104) were seeded in 96-well plates and allowed to grow for 24 h. Subsequently, the cells were exposed to the extracts (culture medium containing eluates from the adhesive discs) for an additional 24 h. Cells not exposed to the extracts were used as a control group. The mitochondrial metabolism was assessed using the MTT assay and the cytokine release evaluated through MAGPIX. The degree of conversion of the adhesives was analyzed using FTIR (n = 5). The results were analyzed by ANOVA two-way and Tukey's test. RESULTS OBU and ZBU eluates caused a statistically significant reduction in mitochondrial metabolism, regardless of the LED used, indicating their cytotoxicity. In contrast, SBU did not significantly affect the MTT results, resembling the control group. A higher release of cytokines IL-1, IL-6, IL-10, and TNF-α were found in association to ZBU. SBU, on the other hand, increased the release of IL-8. OBU did not influenced the cytokine release. SBU presented the higher DC, while OBU and ZBU had similar DC, lower than SBU. SIGNIFICANCE In conclusion, universal adhesives exhibit toxicity towards hDPSCs, but the extent of toxicity varies depending on the adhesive material. ZBU was associated with increased cytokine release, particularly pro-inflammatory mediators, from hDPSCs. The different LEDs did not influenced the cytotoxicity of the evaluated adhesives.
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Affiliation(s)
- Adriano F Lima
- Dental Research Division, Paulista University, Rua Doutor Bacelar, 1212, 04026-002 Sao Paulo, Brazil.
| | | | - Bruna M Fronza
- University of São Paulo, School of Dentistry, Department of Biomaterials and Oral Biology, São Paulo, Brazil
| | - Roberto Ruggiero Braga
- University of São Paulo, School of Dentistry, Department of Biomaterials and Oral Biology, São Paulo, Brazil
| | - Denise Carleto Andia
- Dental Research Division, Paulista University, Rua Doutor Bacelar, 1212, 04026-002 Sao Paulo, Brazil
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12
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Pawłowska M, Mila-Kierzenkowska C. Effect of Alpha-1 Antitrypsin and Irisin on Post-Exercise Inflammatory Response: A Narrative Review. IRANIAN JOURNAL OF MEDICAL SCIENCES 2024; 49:205-218. [PMID: 38680225 PMCID: PMC11053258 DOI: 10.30476/ijms.2023.97480.2925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/12/2023] [Accepted: 02/16/2023] [Indexed: 05/01/2024]
Abstract
Physical activity has a positive effect on human health and emotional well-being. However, in both amateur and professional athletes, training poses a risk of acute or chronic injury through repetitive overloading of bones, joints, and muscles. Inflammation can be an adverse effect of intense exercise caused by several factors including oxidative stress. The present narrative review summarizes current knowledge on inflammatory markers induced by physical exercise. Post-exercise recovery may reduce inflammatory responses and is key to effective training and adaptation of muscle tissues to sustained physical exertion.
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Affiliation(s)
- Marta Pawłowska
- Department of Medical Biology and Biochemistry, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland
| | - Celestyna Mila-Kierzenkowska
- Department of Medical Biology and Biochemistry, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland
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13
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Zhang M, Wang S, Guan Q, Wang J, Yan B, Zhang L, Li D. A bidirectional Mendelian randomization study investigating the relationship between genetically predicted systemic inflammatory regulators and chronic obstructive pulmonary disease. Heliyon 2024; 10:e24109. [PMID: 38268600 PMCID: PMC10806290 DOI: 10.1016/j.heliyon.2024.e24109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Revised: 01/03/2024] [Accepted: 01/03/2024] [Indexed: 01/26/2024] Open
Abstract
Research has shown a connection between inflammation and chronic obstructive pulmonary disease (COPD), however the relationship between inflammation mediators and COPD causation remains unknown. To investigate the causal relationship of mediators of inflammation and COPD, we conducted a two-sample Mendelian randomization (MR) study. In our study, we incorporated 41 regulators of inflammation from 8293 Finnish individuals from genome-wide association studies (GWASs) of COPD corresponding to GWAS summary data for 2115 cases and 454,233 healthy individuals in Europe. Our research validated that higher levels of interleukin 8 (IL-8) are related with a decrease occurrence of COPD (OR = 0.795, 95 % CI = 0.642-0.984, p = 0.035) but that elevated levels of interleukin 18(IL-18) and interleukin 2 (IL-2) may be connected to an amplified risk of COPD (OR = 1.247, 95 % CI = 1.011-1.538; p = 0.039; OR = 1.257, 95 % CI = 1.037-1.523, p = 0.020, respectively). According to our research, cytokines play a crucial role in the development of COPD, and further investigation is necessary to explore the potential of utilizing these cytokines as targets for treatment and prevention of COPD.
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Affiliation(s)
- Mengyuan Zhang
- Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Shengnan Wang
- Department of Neurology, Neuroscience Center, The First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Qingtian Guan
- First Hospital of Jilin University, Jilin University, Changchun, Jilin Province, China
| | - Jianglong Wang
- First Operating Room, The First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Bailing Yan
- Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Li Zhang
- Department of Cardiology, The First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Dan Li
- Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, Jilin Province, China
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14
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Mao Y, Zhang A, Yang H, Zhang C. Identification of IL-8 in CSF as a potential biomarker in sepsis-associated encephalopathy. Cytokine 2023; 172:156390. [PMID: 37812997 DOI: 10.1016/j.cyto.2023.156390] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 09/28/2023] [Accepted: 10/02/2023] [Indexed: 10/11/2023]
Abstract
BACKGROUND Sepsis-associated encephalopathy (SAE) is frequently present at the acute and chronic phase of sepsis, which is characterized by delirium, coma, and cognitive dysfunction. Despite the increased morbidity and mortality of SAE, the pathogenesis of SAE remains unclear. This study aims to discover the potential biomarkers, so as to clear the pathogenesis potentially contributing to the development of SAE and provide new therapeutic strategies for the treatment of SAE. METHODS The GSE135838 dataset was obtained from the Gene Expression Omnibus (GEO) database and utilized for analysis the differentially expressed genes (DEGs). The DEGs were analyzed by limma package of R language and the extracellular protein-differentially expressed genes (EP-DEGs) were screened by the Human Protein Atlas (HPA) and UniProt database. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out to analyze the function and pathway of EP-DEGs. STRING, Cytoscape, MCODE and Cytohubba were used to construct a protein-protein interaction (PPI) network and screen key EP-DEGs. Key EP-DEGs levels were detected in the cerebrospinal fluid (CSF) of SAE patients and non-sepsis patients with critical illness. ROC curve was used to evaluate the diagnostic of SAE. RESULTS We screened 82 EP-DEGs from DEGs. EP-DEGs were enriched in cytokine-cytokine receptor interaction, IL-17 signaling pathway and NOD-like receptor signaling pathway. We identified 2 key extracellular proteins IL-1B and IL-8. We clinically verified that IL-6 and IL-8 levels were increased in CSF of SAE patients and CSF IL-8 (AUC = 0.882, 95 % CI = 0.775-0.988) had a higher accuracy in the diagnosis of SAE than CSF IL-6 (AUC = 0.824, 95 % CI = 0.686-0.961). Furthermore, we found that the IL-8 levels in CSF might not associated with Glasgow Coma Scale (GCS) scores of SAE patients. CONCLUSION IL-8 may be the key extracellular cytokine in the pathogenesis of SAE. Bioinformatics methods were used to explore the biomarkers of SAE and validated the results in clinical samples. Our findings indicate that the IL-8 in CSF might be the potential diagnostic biomarker and therapeutic target in SAE.
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Affiliation(s)
- Yingying Mao
- Department of General Practice, Liaocheng People's Hospital, No.67 West Dongchang Road, Liaocheng 252000, Shandong Province, China
| | - Amin Zhang
- Department of Pediatrics, Qilu Hospital of Shandong University, No.107 West Wenhua Road, Jinan 250012, Shandong Province, China
| | - Haitao Yang
- Department of General Practice, Liaocheng People's Hospital, No.67 West Dongchang Road, Liaocheng 252000, Shandong Province, China
| | - Chen Zhang
- Department of Pediatrics, Qilu Hospital of Shandong University, No.107 West Wenhua Road, Jinan 250012, Shandong Province, China.
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15
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Capogna E, Watne LO, Sørensen Ø, Guichelaar CJ, Idland AV, Halaas NB, Blennow K, Zetterberg H, Walhovd KB, Fjell AM, Vidal-Piñeiro D. Associations of neuroinflammatory IL-6 and IL-8 with brain atrophy, memory decline, and core AD biomarkers - in cognitively unimpaired older adults. Brain Behav Immun 2023; 113:56-65. [PMID: 37400002 DOI: 10.1016/j.bbi.2023.06.027] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 05/31/2023] [Accepted: 06/27/2023] [Indexed: 07/05/2023] Open
Abstract
Concentrations of pro-inflammatory cytokines -interleukin-6 (IL-6) and interleukin-8 (IL-8) - are increased with age and in Alzheimer's disease (AD). It is not clear whether concentrations of IL-6 and IL-8 in the central nervous system predict later brain and cognitive changes over time nor whether this relationship is mediated by core AD biomarkers. Here, 219 cognitively healthy older adults (62-91 years), with baseline cerebrospinal fluid (CSF) measures of IL-6 and IL-8 were followed over time - up to 9 years - with assessments that included cognitive function, structural magnetic resonance imaging, and CSF measurements of phosphorylated tau (p-tau) and amyloid-β (Aβ-42) concentrations (for a subsample). Higher baseline CSF IL-8 was associated with better memory performance over time in the context of lower levels of CSF p-tau and p-tau/Aβ-42 ratio. Higher CSF IL-6 was related to less CSF p-tau changes over time. The results are in line with the hypothesis suggesting that an up-regulation of IL-6 and IL-8 in the brain may play a neuroprotective role in cognitively healthy older adults with lower load of AD pathology.
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Affiliation(s)
- Elettra Capogna
- Centre for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Oslo, Norway.
| | - Leiv Otto Watne
- Department of Geriatric Medicine, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Campus Ahus, Oslo, Norway
| | - Øystein Sørensen
- Centre for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Oslo, Norway
| | - Carlijn Jamila Guichelaar
- Centre for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Oslo, Norway
| | - Ane Victoria Idland
- Oslo Delirium Research Group, Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway
| | - Nathalie Bodd Halaas
- Oslo Delirium Research Group, Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway
| | - Kaj Blennow
- Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
| | - Henrik Zetterberg
- Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK; UK Dementia Research Institute at UCL, London, UK; Hong Center for Neurodegenerative Diseases, Hong Kong, China; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
| | - Kristine Beate Walhovd
- Centre for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Oslo, Norway; Computational Radiology and Artificial Intelligence, Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway
| | - Anders Martin Fjell
- Centre for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Oslo, Norway; Computational Radiology and Artificial Intelligence, Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway
| | - Didac Vidal-Piñeiro
- Centre for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Oslo, Norway
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Carvalho T, Landim MG, Lima MLD, Bittar C, Faria BCDAO, Rahal P, de Lima MCF, Junior VFDV, Joanitti GA, Calmon MF. Synthesis of copaiba (Copaifera officinalis) oil nanoemulsion and the potential against Zika virus: An in vitro study. PLoS One 2023; 18:e0283817. [PMID: 37676868 PMCID: PMC10484457 DOI: 10.1371/journal.pone.0283817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 03/19/2023] [Indexed: 09/09/2023] Open
Abstract
Zika virus (ZIKV) has spread all over the world since its major outbreak in 2015. This infection has been recognized as a major global health issue due to the neurological complications related to ZIKV infection, such as Guillain-Barré Syndrome and Zika virus Congenital Syndrome. Currently, there are no vaccines or specific treatments for ZIKV infection, which makes the development of specific therapies for its treatment very important. Several studies have been developed to analyze the potential of compounds against ZIKV, with the aim of finding new promising treatments. Herein, we evaluate the ability of a copaiba (Copaifera officinalis) oil nanoemulsion (CNE) to inhibit ZIKV. First, the highest non-cytotoxic concentration of 180 μg/mL was chosen since this concentration maintains 80% cell viability up to 96h after treatment with CNE in VERO cells resulted from MTT assay. The intracellular uptake assay was performed, and confirmed the internalization of the nanoemulsion in cells at all times analyzed. VERO cells were infected with ZIKV and simultaneously treated with CNE and the nanoformulation without oil (ENE) at the highest non-toxic concentration. The results evaluated by plaque assay revealed a viral inhibition of 80% for CNE and 70% for ENE. A dose-dependence assay revealed that the CNE treatment demonstrated a dose-dependent response in the viral RNA levels, whereas all ENE tested concentrations exhibited a similar degree of reduction. Taken together, our results suggest CNE as a promising nano-sized platform to be further studied for antiviral treatments.
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Affiliation(s)
- Tamara Carvalho
- Department of Biology, São Paulo State University—UNESP, Rua Cristóvão Colombo, São José do Rio Preto, Brazil
| | - Marcela Guimarães Landim
- Laboratory of Bioactive Compounds and Nanobiotechnology (LBCNano), University of Brasilia, Campus Universitário – Centro Metropolitano, Ceilândia Sul, Brasília, Federal District, Brazil
- Post-Graduation Program in Nanoscience and Nanobiotechnology, Institute of Biological Sciences, University of Brasilia, Campus Universitário Darcy Ribeiro, Brasília, Brazil
| | - Maria Letícia Duarte Lima
- Department of Biology, São Paulo State University—UNESP, Rua Cristóvão Colombo, São José do Rio Preto, Brazil
| | - Cíntia Bittar
- Department of Biology, São Paulo State University—UNESP, Rua Cristóvão Colombo, São José do Rio Preto, Brazil
| | - Beatriz Carvalho de Araújo Oliveira Faria
- Laboratory of Bioactive Compounds and Nanobiotechnology (LBCNano), University of Brasilia, Campus Universitário – Centro Metropolitano, Ceilândia Sul, Brasília, Federal District, Brazil
- Post-Graduation Program in Nanoscience and Nanobiotechnology, Institute of Biological Sciences, University of Brasilia, Campus Universitário Darcy Ribeiro, Brasília, Brazil
| | - Paula Rahal
- Department of Biology, São Paulo State University—UNESP, Rua Cristóvão Colombo, São José do Rio Preto, Brazil
| | | | | | - Graziella Anselmo Joanitti
- Laboratory of Bioactive Compounds and Nanobiotechnology (LBCNano), University of Brasilia, Campus Universitário – Centro Metropolitano, Ceilândia Sul, Brasília, Federal District, Brazil
- Post-Graduation Program in Nanoscience and Nanobiotechnology, Institute of Biological Sciences, University of Brasilia, Campus Universitário Darcy Ribeiro, Brasília, Brazil
| | - Marilia Freitas Calmon
- Department of Biology, São Paulo State University—UNESP, Rua Cristóvão Colombo, São José do Rio Preto, Brazil
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Ferreira IA, Peixoto D, Losada AP, Quiroga MI, do Vale A, Costas B. Early innate immune responses in European sea bass ( Dicentrarchus labrax L.) following Tenacibaculum maritimum infection. Front Immunol 2023; 14:1254677. [PMID: 37731496 PMCID: PMC10507263 DOI: 10.3389/fimmu.2023.1254677] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 08/15/2023] [Indexed: 09/22/2023] Open
Abstract
Introduction The marine aquaculture industry has been witnessing a worldwide emergence of tenacibaculosis, a poorly understood bacterial disease caused by Tenacibaculum maritimum that affects commercially important fish. So far, knowledge on the T. maritimum virulence mechanisms is scarce and the pathogen-host interaction operating in tenacibaculosis remain to be disclosed. This study aimed at contributing to a better understanding of this disease, by evaluating the early innate immune response triggered in European sea bass (Dicentrarchus labrax) by a bath-challenge with T. maritimum. Methods Groups of sea bass were bath-challenged with T. maritimum (challenged fish) or mock-challenged. Undisturbed fish were used as controls (time 0). Samples of blood, liver and mucosal organs (skin, gills and posterior-intestine) were collected at 0 h (control) and at 6, 24, 48 and 72 h post-challenge (n=12). Mucosal organs were used for analyzing the expression of immune-related genes by RT-qPCR, as well as blood samples for assessing haematological and innate humoral parameters and liver for oxidative stress assessment. Results An increased expression of il-1β, il8, mmp9 and hamp1 was detected in all mucosal organs of infected fish when compared with control and mock-challenged fish, suggesting a pro-inflammatory response against T. maritimum transversal to all organs. The faster induction of these pro-inflammatory genes was observed in the gills. Regarding the systemic response, challenged fish presented neutrophilia, monocytosis, signs of anemia, and a decrease of bactericidal and lysozyme activities in plasma. Almost no variations were observed regarding hepatic oxidative stress. Discussion/Conclusions The present study suggests that T. maritimum induces a local innate immune response upon bath infection not only in the skin of European sea bass, but also in the gills and posterior-intestine, likely triggered by the T. maritimum's capacity to adhere, colonize and damage these organs that can function as entry ways to bacteria, leading ultimately to the seen host's systemic response.
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Affiliation(s)
- Inês A. Ferreira
- Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal
- Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto, Porto, Portugal
- Fish Immunology and Vaccinology Group, IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
| | - Diogo Peixoto
- Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal
- Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto, Porto, Portugal
| | - Ana Paula Losada
- Departamento de Anatomía, Produción Animal e Ciencias Clínicas Veterinarias, Facultade de Veterinaria, Universidade de Santiago de Compostela, Lugo, Spain
| | - María Isabel Quiroga
- Departamento de Anatomía, Produción Animal e Ciencias Clínicas Veterinarias, Facultade de Veterinaria, Universidade de Santiago de Compostela, Lugo, Spain
| | - Ana do Vale
- Fish Immunology and Vaccinology Group, IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
| | - Benjamín Costas
- Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal
- Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto, Porto, Portugal
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Eriksen E, Afanou AK, Straumfors A, Graff P. Bioaerosol-induced in vitro activation of toll-like receptors and inflammatory biomarker expression in waste workers. Int Arch Occup Environ Health 2023; 96:985-998. [PMID: 37243736 PMCID: PMC10361871 DOI: 10.1007/s00420-023-01984-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 05/15/2023] [Indexed: 05/29/2023]
Abstract
PURPOSE Occupational exposure to bioaerosols during waste handling remains a health concern for exposed workers. However, exposure-related health effects and underlying immunological mechanisms are still poorly described. METHODS The present study assessed the inflammatory potential of work-air samples (n = 56) in vitro and investigated biomarker expression in exposed workers (n = 69) compared to unexposed controls (n = 25). These quantitative results were compared to self-reported health conditions. RESULTS Personal air samples provoked an activation of TLR2 and TLR4 HEK reporter cells in one-third of all samples, indicating that the work environment contained ligands capable of inducing an immune response in vitro. Monocyte levels, as well as plasma biomarker levels, such as IL-1Ra, IL-18 and TNFα were significantly higher in exposed workers, compared to the control group when confounding factors such as BMI, sex, age and smoking habits were accounted for. Furthermore, a significant exposure-related increase in midweek IL-8 levels was measured among exposed workers. Tendencies of increased prevalence of health effects of the respiratory tract were identified in exposed workers. CONCLUSION Inhalable dust provoked TLR activation in vitro, indicating that an exposure-related immune response may be expected in susceptible workers. However, despite significant differences in inflammatory plasma biomarker levels between exposed and unexposed workers, prevalence of self-reported health effects did not differ between the groups. This may be due to the healthy worker effect, or other factors such as adequate use of personal protective respiratory devices or adaptation to the work environment with reduced activation of the immune system.
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Affiliation(s)
- Elke Eriksen
- STAMI, National Institute of Occupational Health, Gydas Vei 8, 0363, Oslo, Norway.
| | - Anani Komlavi Afanou
- STAMI, National Institute of Occupational Health, Gydas Vei 8, 0363, Oslo, Norway
| | - Anne Straumfors
- STAMI, National Institute of Occupational Health, Gydas Vei 8, 0363, Oslo, Norway
| | - Pål Graff
- STAMI, National Institute of Occupational Health, Gydas Vei 8, 0363, Oslo, Norway
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Montero DA, Vidal RM, Velasco J, George S, Lucero Y, Gómez LA, Carreño LJ, García-Betancourt R, O’Ryan M. Vibrio cholerae, classification, pathogenesis, immune response, and trends in vaccine development. Front Med (Lausanne) 2023; 10:1155751. [PMID: 37215733 PMCID: PMC10196187 DOI: 10.3389/fmed.2023.1155751] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 04/14/2023] [Indexed: 05/24/2023] Open
Abstract
Vibrio cholerae is the causative agent of cholera, a highly contagious diarrheal disease affecting millions worldwide each year. Cholera is a major public health problem, primarily in countries with poor sanitary conditions and regions affected by natural disasters, where access to safe drinking water is limited. In this narrative review, we aim to summarize the current understanding of the evolution of virulence and pathogenesis of V. cholerae as well as provide an overview of the immune response against this pathogen. We highlight that V. cholerae has a remarkable ability to adapt and evolve, which is a global concern because it increases the risk of cholera outbreaks and the spread of the disease to new regions, making its control even more challenging. Furthermore, we show that this pathogen expresses several virulence factors enabling it to efficiently colonize the human intestine and cause cholera. A cumulative body of work also shows that V. cholerae infection triggers an inflammatory response that influences the development of immune memory against cholera. Lastly, we reviewed the status of licensed cholera vaccines, those undergoing clinical evaluation, and recent progress in developing next-generation vaccines. This review offers a comprehensive view of V. cholerae and identifies knowledge gaps that must be addressed to develop more effective cholera vaccines.
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Affiliation(s)
- David A. Montero
- Departamento de Microbiología, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile
| | - Roberto M. Vidal
- Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
- Instituto Milenio de Inmunología e Inmunoterapia, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Juliana Velasco
- Unidad de Paciente Crítico, Clínica Hospital del Profesor, Santiago, Chile
- Programa de Formación de Especialista en Medicina de Urgencia, Universidad Andrés Bello, Santiago, Chile
| | - Sergio George
- Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Yalda Lucero
- Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
- Departamento de Pediatría y Cirugía Infantil, Hospital Dr. Roberto del Rio, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Leonardo A. Gómez
- Departamento de Microbiología, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile
| | - Leandro J. Carreño
- Instituto Milenio de Inmunología e Inmunoterapia, Facultad de Medicina, Universidad de Chile, Santiago, Chile
- Programa de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Richard García-Betancourt
- Programa de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Miguel O’Ryan
- Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
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20
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Agostinelli BG, Andia DC, Lima AF. Co-initiators of polymerization can modulate the inflammatory cytokine release without major cytotoxic effects in human dental pulp cells. J Biomed Mater Res B Appl Biomater 2023; 111:1112-1120. [PMID: 36598816 DOI: 10.1002/jbm.b.35218] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 11/16/2022] [Accepted: 12/23/2022] [Indexed: 01/05/2023]
Abstract
To evaluate the cytotoxicity of co-initiators of polymerization and its influence on cytokine release from human dental pulp cells (hDPCs). Cells were isolated from the dental pulp of sound human third molars. The co-initiators dimethylaminoethyl amine benzoate-(EDAB), 2-(dimethylamino)ethyl methacrylate (DMAEMA); 2-Ethylhexyl 4-(dimethylamino)benzoate (EHA) and bis(4-methyl phenyl)iodonium hexafluorophosphate (BPI) were diluted in dimethylsulfoxide (DMSO) at different concentrations. In this way, experimental groups and one control (without treatment) were obtained. hDPCs (10 × 104 cell per well) were seeded on 96 well plates and incubated at 37°C and 5% CO2 for 48 h. After this, the cells were exposed to different concentrations of co-initiators cited for 24 h. After this time, the culture medium was removed, and the mitochondrial metabolism was evaluated by MTT assay, cell death by flow cytometry, and cytokine released (IL-1β, IL6, IL-8, IL-10, and TNF-α) was analyzed by MAGPIX assay. The data were analyzed by ANOVA one-way and Tukey's test. EHA, DMAEMA, and EDAB did not reduce the mitochondrial metabolism. BPI presented high toxicity with remarkable reduction (80%) after exposure to 1 mM. The cell death of all test groups was similar to control. After 24 h treatment, the IL-8 was up-regulated by all compounds, while IL-6 was upregulated after exposure to EHA and downregulated after DMAEMA stimulation. BPI, EHA, EDAB, and DMAEMA can trigger an initial inflammatory response, upregulating the IL-8 secretion in hDPCs in a compound-concentration-dependent manner; however, this was not accompanied by major cytotoxic effects at cell death or mitochondrial-metabolism levels.
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Affiliation(s)
| | | | - Adriano F Lima
- Dental Research Division, Paulista University, Sao Paulo, Brazil
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21
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Thai THN, Nguyen HP, Nguyen THY, Nguyen TBH, Nguyen TH, Nguyen TMN, Ha TMT. Genetic diversity of the oipA gene among Helicobacter pylori isolates and clinical outcome in Vietnam. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2023; 112:105438. [PMID: 37105346 DOI: 10.1016/j.meegid.2023.105438] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Revised: 04/19/2023] [Accepted: 04/22/2023] [Indexed: 04/29/2023]
Abstract
Outer inflammatory protein A (OipA), which is encoded by the oipA gene, can induce interleukin-8 secretion in gastric epithelial cells. The functional status of the oipA gene is regulated by the slipped-strand mispairing mechanism based on the CT dinucleotide repeat number in the 5' region. This study aimed to investigate the oipA functional status ("on/off") of Helicobacter pylori (H. pylori) and its association with gastroduodenal diseases in southwestern Vietnam. The cross-sectional study was conducted on 173H. pylori isolates from 173 patients with gastroduodenal diseases. Sanger sequencing was used to determine the functional status of oipA. Multivariable logistic regression analysis was performed to identify the association between oipA status and gastroduodenal diseases. The oipA "on" status accounted for 96% of H. pylori isolates. Twenty-five CT repeat patterns of the oipA 5' signal region were observed, five of which were novel CT repeat patterns. The oipA "on" status was found in 100%, 97.8%, and 86.8% of H. pylori isolates from patients with peptic ulcer, precancerous lesions, and chronic gastritis, respectively (p < 0.01). The oipA "on" status was related to gastric precancerous lesions versus chronic gastritis (adjusted OR = 7.39, 95% CI: 1.35-40.59, p = 0.021) and peptic ulcers versus chronic gastritis (adjusted OR = 12.79, 95% CI: 1.19-1760.32, p = 0.033). Our data show a high prevalence of the oipA "on" status, which was associated with precancerous gastric lesions and peptic ulcers. Moreover, genetic diversity in the number and pattern of CT dinucleotide repeat of oipA among Vietnamese H. pylori strains was identified.
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Affiliation(s)
- Thi Hong Nhung Thai
- Department of Internal Medicine, University of Medicine and Pharmacy, Hue University, Hue, Viet Nam; Department of Internal Medicine, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho, Viet Nam
| | - Hong Phong Nguyen
- Department of Pathology and Forensic Medicine, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho, Viet Nam
| | - Thi Hai Yen Nguyen
- Department of Microbiology, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho, Viet Nam
| | - Thi Be Hai Nguyen
- Department of Microbiology, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho, Viet Nam
| | - Thai Hoa Nguyen
- Department of Internal Medicine, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho, Viet Nam
| | - Thi Mai Ngan Nguyen
- Department of Medical Genetics, University of Medicine and Pharmacy, Hue University, Hue, Viet Nam
| | - Thi Minh Thi Ha
- Department of Medical Genetics, University of Medicine and Pharmacy, Hue University, Hue, Viet Nam; Institute of Biomedicine, University of Medicine and Pharmacy, Hue University, Hue, Viet Nam.
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22
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Valmorbida A, Longo GZ, Nascimento GM, de Oliveira LL, de Moraes Trindade EBS. Association between cytokine levels and anthropometric measurements: a population-based study. Br J Nutr 2023; 129:1119-1126. [PMID: 35856255 DOI: 10.1017/s0007114522002148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Obesity is currently considered a public health problem with pandemic proportions and is associated with chronic low-grade inflammation, which can predispose to the development of several chronic diseases and metabolic complications. This cross-sectional population-based study, conducted with 743 Brazilian adults, aimed to evaluate the association between inflammatory cytokines with anthropometric measurements. Socio-demographic, anthropometric, behavioural and biochemical variables were collected. Multiple linear regression stratified by sex and adjusted for confounding factors was performed. In men, waist circumference (WC) was associated with IL-1β (3·52 pg/ml; 95 % CI 0·60, 6·45), IL-6 (6·35 pg/ml; 95 % CI 0·35, 12·34), IL-8 (8·77 pg/ml; 95 % CI 2·37, 15·17), IL-10 (3·09 pg/ml; 95 % CI 0·56, 5·61), IL12p70 (8·31 pg/ml; 95 % CI 3·11, 13·52) and TNF-α (4·22 pg/ml; 95 % CI 0·20, 10·48). Waist:height ratio was associated with IL-6 (3·21 pg/ml; 95 % CI 0·02, 6·39). BMI was associated with IL-1β (1·50 pg/ml; 95 % CI 0·46, 2·34), IL-6 (2·97 pg/ml; 95 % CI 0·78, 5·16), IL-8 (4·48 pg/ml; 95 % CI 2·21, 6·75), IL-10 (1·31 pg/ml; 95 % CI 0·30, 2·31), IL-12p70 (3·59 pg/ml; 95 % CI 1·24, 5·95) and TNF-α (2·00 pg/ml; 95 % CI 0·81, 3·19). In women, WC was associated with IL-6 (5·10 pg/ml; 95 % CI 0·68, 9·51) and IL-10 (4·16 pg/ml; 95 % CI 1·26, 7·06). BMI was associated with IL-6 (2·67 pg/ml; 95 % CI 0·34, 4·99), and WHR was associated with TNF-α (2·84 pg/ml; 95 % IC 0·86-6·54). The results highlight the importance of anthropometric assessment in clinical practice and the need to develop public policies and interventions to reduce the prevalence of obesity and, consequently, of inflammation and possible metabolic complications.
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Affiliation(s)
- Aline Valmorbida
- Graduate Program in Nutrition, Federal University of Santa Catarina, Florianópolis, Brazil
| | - Giana Zarbato Longo
- Graduate Program in Nutrition, Federal University of Santa Catarina, Florianópolis, Brazil
- Department of Nutrition, Federal University of Santa Catarina, Florianópolis, Brazil
| | | | | | - Erasmo Benicio Santos de Moraes Trindade
- Graduate Program in Nutrition, Federal University of Santa Catarina, Florianópolis, Brazil
- Department of Nutrition, Federal University of Santa Catarina, Florianópolis, Brazil
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23
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Ding Y, Yang Y, Xue L. Immune cells and their related genes provide a new perspective on the common pathogenesis of ankylosing spondylitis and inflammatory bowel diseases. Front Immunol 2023; 14:1137523. [PMID: 37063924 PMCID: PMC10101339 DOI: 10.3389/fimmu.2023.1137523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 03/21/2023] [Indexed: 04/03/2023] Open
Abstract
BackgroundThe close relationship between ankylosing spondylitis (AS) and inflammatory bowel diseases (IBD) has been supported by many aspects, including but not limited to clinical manifestations, epidemiology and pathogenesis. Some evidence suggests that immune cells actively participated in the pathogenesis of both diseases. However, information on which cells are primarily involved in this process and how these cells mobilize, migrate and interact is still limited.MethodsDatasets were downloaded from Gene Expression Omnibus (GEO) database. Common differentially expressed genes (coDEGs) were identified by package “limma”. The protein-protein interaction (PPI) network and Weighted Gene Co-Expression Network Analysis (WGCNA) were used to analyze the interactions between coDEGs. KEGG pathway enrichment analysis and inverse cumulative distribution function were applied to identify common differential pathways, while Gene Set Enrichment Analysis (GSEA) was used to confirm the significance. Correlation analysis between coDEGs and immune cells led to the identification of critical immune-cell-related coDEGs. The diagnostic models were established based on least absolute shrinkage and selection operator (LASSO) regression, while receiver operating characteristic (ROC) analysis was used to identify the ability of the model. Validation datasets were imported to demonstrate the significant association of coDEGs with specific immune cells and the capabilities of the diagnostic model.ResultsIn total, 67 genes were up-regulated and 185 genes were down-regulated in both diseases. Four down-regulated pathways and four up-regulated pathways were considered important. Up-regulated coDEGs were firmly associated with neutrophils, while down-regulated genes were significantly associated with CD8+ T−cells and CD4+ T−cells in both AS and IBD datasets. Five up-regulated and six down-regulated key immue-cell-related coDEGs were identified. Diagnostic models based on key immue-cell-related coDEGs were established and tested. Validation datasets confirmed the significance of the correlation between coDEGs and specific immune cells.ConclusionThis study provides fresh insights into the co-pathogenesis of AS and IBD. It is proposed that neutrophils and T cells may be actively involved in this process, however, in opposite ways. The immue-cell-related coDEGs, revealed in this study, may be relevant to their regulation, although relevant research is still lacking.
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24
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Zhang Y, Wang J, Ye Y, Zou Y, Chen W, Wang Z, Zou Z. Peripheral cytokine levels across psychiatric disorders: A systematic review and network meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry 2023; 125:110740. [PMID: 36893912 DOI: 10.1016/j.pnpbp.2023.110740] [Citation(s) in RCA: 44] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Revised: 02/27/2023] [Accepted: 03/04/2023] [Indexed: 03/11/2023]
Abstract
Immune dysregulated cytokine production is involved in mental diseases. However, the results are inconsistent and the pattern of cytokine alterations has not been compared across disorders. We performed a network impact analysis of cytokine levels for different psychiatric disorders including schizophrenia, major depressive disorder, bipolar disorder, panic disorder, post-traumatic stress disorder and obsessive compressive disorder to evaluate their clinical impact across conditions. Studies were identified by searching the electronic databases up to 31/05/2022. A total of eight cytokines, together with (high-sensitivity) C-reactive proteins (hsCRP/CRP) were included in the network meta-analysis. The levels of proinflammatory cytokines, hsCRP/CRP and interleukin 6 (IL-6) were significantly increased in patients with psychiatric disorders when compared to controls. IL-6 showed no significant difference among comparisons between disorders according to the network meta-analysis. Interleukin 10 (IL-10) is significantly increased in patients with bipolar disorder compared to major depressive disorder. Further, the level of interleukin-1 beta (IL-1β) was significantly increased in major depressive disorder as compared to bipolar disorder. The level of interleukin 8 (IL-8) varied among these psychiatric disorders based on the network meta-analysis result. Overall, abnormal cytokine levels were found in psychiatric disorders, and some of the cytokines displayed differential characteristics in these disorders, especially IL-8, pointing to a role as potential biomarkers for general and differential diagnosis.
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Affiliation(s)
- Yuan Zhang
- Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China
| | | | - Yu Ye
- Sichuan Provincial Center for Mental Health, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China
| | - Yazhu Zou
- Sichuan Provincial Center for Mental Health, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China
| | - Wei Chen
- Sichuan Provincial Center for Mental Health, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China
| | - Zuxing Wang
- Sichuan Provincial Center for Mental Health, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China
| | - Zhili Zou
- Sichuan Provincial Center for Mental Health, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China; Key Laboratory of psychosomatic medicine, Chinese Academy of Medical Sciences, Chengdu, Sichuan, China.
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25
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Santos CNO, Magalhães LS, Fonseca ABDL, Bispo AJB, Porto RLS, Alves JC, Dos Santos CA, de Carvalho JV, da Silva AM, Teixeira MM, de Almeida RP, Dos Santos PL, de Jesus AR. Association between genetic variants in TREM1, CXCL10, IL4, CXCL8 and TLR7 genes with the occurrence of congenital Zika syndrome and severe microcephaly. Sci Rep 2023; 13:3466. [PMID: 36859461 PMCID: PMC9975867 DOI: 10.1038/s41598-023-30342-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 02/21/2023] [Indexed: 03/03/2023] Open
Abstract
Congenital Zika syndrome (CZS) is a cluster of malformations induced by Zika virus (ZIKV) infection and the underline mechanisms involved in its occurrence are yet not fully understood. Along with epidemiological and environmental factors, the genetic host factors are suggested as important to the CZS occurrence and development, however, few studies have evaluated this. This study enrolled a total of 245 individuals in a case-control association study compound a cohort of high specific interest constituted by 75 mothers who had delivered CZS infants, their 76 infants, and 47 mothers that had delivered healthy infants, and their 47 infants. Sixteen single-nucleotide polymorphisms on TREM1, CXCL10, IL4, CXCL8, TLR3, TLR7, IFNR1, CXCR1, IL10, CCR2 and CCR5 genes were genotyped to investigate their association as risk factors to CZS. The results show an association between C allele at TREM1 rs2234246 and C allele at IL4 rs224325 in mothers infected with ZIKV during pregnancy, with the increased susceptibility to CZS occurrence in their infants and the SNP CXCL8 rs4073 and the G allele at CXCL10 rs4508917 with presence of CZS microcephaly in the infants. Furthermore, the T allele at CXCL8 rs4073 and TRL7 rs179008 SNPs were associated with the severity of microcephaly in children with CZS. These results suggest that these polymorphisms in genes of innate immune responses addressed here are associated to increased risk of occurrence and severity of CZS in pregnant mothers infected with ZIKV and their CZS infants.
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Affiliation(s)
- Camilla Natália Oliveira Santos
- Immunology and Molecular Biology Laboratory and Graduate Program in Health Sciences, University Hospital of Federal University of Sergipe, Aracaju, Brazil.
| | - Lucas Sousa Magalhães
- Immunology and Molecular Biology Laboratory and Graduate Program in Health Sciences, University Hospital of Federal University of Sergipe, Aracaju, Brazil
- Sector of Parasitology and Pathology, Biological and Health Sciences Institute, Federal University of Alagoas, Maceió, Brazil
| | | | | | | | - Juliana Cardoso Alves
- Immunology and Molecular Biology Laboratory and Graduate Program in Health Sciences, University Hospital of Federal University of Sergipe, Aracaju, Brazil
| | | | | | - Angela Maria da Silva
- Immunology and Molecular Biology Laboratory and Graduate Program in Health Sciences, University Hospital of Federal University of Sergipe, Aracaju, Brazil
- Department of Medicine of University Hospital, Federal University of Sergipe, Aracaju, Brazil
| | | | - Roque Pacheco de Almeida
- Immunology and Molecular Biology Laboratory and Graduate Program in Health Sciences, University Hospital of Federal University of Sergipe, Aracaju, Brazil
- Department of Medicine of University Hospital, Federal University of Sergipe, Aracaju, Brazil
| | - Priscila Lima Dos Santos
- Immunology and Molecular Biology Laboratory and Graduate Program in Health Sciences, University Hospital of Federal University of Sergipe, Aracaju, Brazil
| | - Amélia Ribeiro de Jesus
- Immunology and Molecular Biology Laboratory and Graduate Program in Health Sciences, University Hospital of Federal University of Sergipe, Aracaju, Brazil
- Department of Medicine of University Hospital, Federal University of Sergipe, Aracaju, Brazil
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26
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Cai Y, Zhu ZH, Li RH, Yin XY, Chen RF, Man LJ, Hou WL, Zhu HL, Wang J, Zhang H, Jia QF, Hui L. Association between increased serum interleukin-8 levels and improved cognition in major depressive patients with SSRIs. BMC Psychiatry 2023; 23:122. [PMID: 36823619 PMCID: PMC9948487 DOI: 10.1186/s12888-023-04616-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 02/19/2023] [Indexed: 02/25/2023] Open
Abstract
BACKGROUND The effect of neuroinflammatory cytokines on cognitive deficits in patients with major depressive disorder (MDD) can be altered by selective serotonin reuptake inhibitors (SSRIs). This study aimed to examine serum interleukin-8 (IL-8) levels, cognitive function, and their associations in MDD patients with SSRIs. METHODS Thirty SSRI-treated MDD patients and 101 healthy controls were recruited for this study. We examined cognitive performance using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum IL-8 levels using the Human Inflammatory Cytokine Cytometric Bead Array in both cases and controls. RESULTS The RBANS test scores were significantly lower in MDD patients with SSRIs than in healthy controls after controlling for covariates (all p < 0.001). Serum levels of IL-8 were higher in MDD patients with SSRIs than in healthy controls after adjusting for covariates (F = 3.82, p = 0.05). Serum IL-8 levels were positively correlated with sub-scores of delayed memory (r = 0.37, p = 0.04) and visuospatial/constructional (r = 0.43, p = 0.02) in MDD patients with SSRIs but not in in healthy controls (delayed memory score: r = -0.12, p = 0.24; visuospatial/constructional score: r = 0.02, p = 0.81). CONCLUSIONS Our findings suggested that increased serum IL-8 level might not only be involved in the MDD psychopathology or the use of SSRIs but also correspond to improving MDD delayed memory and visuospatial/constructional function.
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Affiliation(s)
- Yuan Cai
- grid.268099.c0000 0001 0348 3990School of Mental Health, Wenzhou Medical University, Wenzhou, 325035 Zhejiang People’s Republic of China ,grid.263761.70000 0001 0198 0694Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow University, No. 11 Guangqian Road, Suzhou, 215137 Jiangsu People’s Republic of China
| | - Zhen Hua Zhu
- grid.263761.70000 0001 0198 0694Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow University, No. 11 Guangqian Road, Suzhou, 215137 Jiangsu People’s Republic of China
| | - Rong Hua Li
- grid.263761.70000 0001 0198 0694Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow University, No. 11 Guangqian Road, Suzhou, 215137 Jiangsu People’s Republic of China
| | - Xu Yuan Yin
- grid.263761.70000 0001 0198 0694Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow University, No. 11 Guangqian Road, Suzhou, 215137 Jiangsu People’s Republic of China
| | - Ru Feng Chen
- grid.263761.70000 0001 0198 0694Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow University, No. 11 Guangqian Road, Suzhou, 215137 Jiangsu People’s Republic of China
| | - Li Juan Man
- grid.263761.70000 0001 0198 0694Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow University, No. 11 Guangqian Road, Suzhou, 215137 Jiangsu People’s Republic of China
| | - Wen Long Hou
- grid.263761.70000 0001 0198 0694Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow University, No. 11 Guangqian Road, Suzhou, 215137 Jiangsu People’s Republic of China
| | - Hong Liang Zhu
- grid.263761.70000 0001 0198 0694Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow University, No. 11 Guangqian Road, Suzhou, 215137 Jiangsu People’s Republic of China
| | - Jing Wang
- grid.263761.70000 0001 0198 0694Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow University, No. 11 Guangqian Road, Suzhou, 215137 Jiangsu People’s Republic of China
| | - Huiping Zhang
- grid.189504.10000 0004 1936 7558Departments of Psychiatry and Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118-2526 USA
| | - Qiu Fang Jia
- Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow University, No. 11 Guangqian Road, Suzhou, 215137, Jiangsu, People's Republic of China.
| | - Li Hui
- School of Mental Health, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, People's Republic of China. .,Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow University, No. 11 Guangqian Road, Suzhou, 215137, Jiangsu, People's Republic of China.
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27
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Costa A, van der Stelt I, Reynés B, Konieczna J, Fiol M, Keijer J, Palou A, Romaguera D, van Schothorst EM, Oliver P. Whole-Genome Transcriptomics of PBMC to Identify Biomarkers of Early Metabolic Risk in Apparently Healthy People with Overweight-Obesity and in Normal-Weight Subjects. Mol Nutr Food Res 2023; 67:e2200503. [PMID: 36564895 DOI: 10.1002/mnfr.202200503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
SCOPE Peripheral blood mononuclear cells (PBMC) provide a useful and minimally invasive source of biomarkers. Here to identify PBMC transcriptomic biomarkers predictive of metabolic impairment related to increased adiposity is aimed. METHODS AND RESULTS The study analyzed the global PBMC transcriptome in metabolically healthy (normoglycemic) volunteers with overweight-obesity (OW-OB, n = 12), and in subjects with metabolically obese normal-weight (MONW, n = 5) phenotype, in comparison to normal-weight (NW, n = 12) controls. The study identifies 1072 differentially expressed genes (DEGs) in OW-OB versus NW and 992 in MONW versus NW. Hierarchical clustering of the top 100 DEGs clearly distinguishes OW-OB and MONW from NW. Remarkably, the OW-OB and MONW phenotypes share 257 DEGs regulated in the same direction. The top up-regulated gene CXCL8, coding for interleukin 8, with a role in obesity-related pathologies, is of special interest as a potential marker for predicting increased metabolic risk. CXCL8 expression is increased mainly in the MONW group and correlated directly with C-reactive protein levels. CONCLUSIONS PBMC gene expression analysis of CXCL8 or a pool of DEGs may be used to identify early metabolic risk in an apparently healthy population regardless of their BMI, i.e., subjects with OW-OB or MONW phenotype and to apply adequate and personalized nutritional preventive strategies.
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Affiliation(s)
- Andrea Costa
- Nutrigenomics, Biomarkers and Risk Evaluation (NuBE) group, University of the Balearic Islands (UIB), Palma, Mallorca, 07122, Spain.,Health Research Institute of the Balearic Islands (IdISBa), Palma, Mallorca, 07010, Spain.,CIBER of Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, 28029, Spain
| | - Inge van der Stelt
- Human and Animal Physiology, Wageningen University, Wageningen, 6708, The Netherlands
| | - Bàrbara Reynés
- Nutrigenomics, Biomarkers and Risk Evaluation (NuBE) group, University of the Balearic Islands (UIB), Palma, Mallorca, 07122, Spain.,Health Research Institute of the Balearic Islands (IdISBa), Palma, Mallorca, 07010, Spain.,CIBER of Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, 28029, Spain
| | - Jadwiga Konieczna
- Health Research Institute of the Balearic Islands (IdISBa), Palma, Mallorca, 07010, Spain.,CIBER of Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, 28029, Spain.,Research Group on Nutritional Epidemiology & Cardiovascular Physiopathology (NUTRECOR), University Hospital Son Espases (HUSE), Palma, Mallorca, 07120, Spain
| | - Miquel Fiol
- Health Research Institute of the Balearic Islands (IdISBa), Palma, Mallorca, 07010, Spain.,CIBER of Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, 28029, Spain.,Research Group on Nutritional Epidemiology & Cardiovascular Physiopathology (NUTRECOR), University Hospital Son Espases (HUSE), Palma, Mallorca, 07120, Spain
| | - Jaap Keijer
- Human and Animal Physiology, Wageningen University, Wageningen, 6708, The Netherlands
| | - Andreu Palou
- Nutrigenomics, Biomarkers and Risk Evaluation (NuBE) group, University of the Balearic Islands (UIB), Palma, Mallorca, 07122, Spain.,Health Research Institute of the Balearic Islands (IdISBa), Palma, Mallorca, 07010, Spain.,CIBER of Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, 28029, Spain
| | - Dora Romaguera
- Health Research Institute of the Balearic Islands (IdISBa), Palma, Mallorca, 07010, Spain.,CIBER of Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, 28029, Spain.,Research Group on Nutritional Epidemiology & Cardiovascular Physiopathology (NUTRECOR), University Hospital Son Espases (HUSE), Palma, Mallorca, 07120, Spain
| | | | - Paula Oliver
- Nutrigenomics, Biomarkers and Risk Evaluation (NuBE) group, University of the Balearic Islands (UIB), Palma, Mallorca, 07122, Spain.,Health Research Institute of the Balearic Islands (IdISBa), Palma, Mallorca, 07010, Spain.,CIBER of Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, 28029, Spain
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Jin Z, Li S, Li R, Song X, Zhang S, Sun Y, Tao F, Wan Y. Gender- and age-specific associations of childhood maltreatment with peripheral serum inflammatory cytokines in middle school students. Front Immunol 2023; 14:1067291. [PMID: 36798120 PMCID: PMC9927207 DOI: 10.3389/fimmu.2023.1067291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 01/19/2023] [Indexed: 02/04/2023] Open
Abstract
Background The impact of childhood maltreatment on multiple inflammatory cytokines among middle school students remains to be elucidated. This study aimed to examine the associations of different types of childhood maltreatment with peripheral serum inflammatory cytokines (interleukin-10, interleukin-1β, interleukin-6, interleukin-8, and tumor necrosis factor-α) in middle school students, and to explore the differences in these associations between boys and girls and between late (≥15 and<20 years) and early (≥11 and <15 years) adolescence. Methods A total of 1122 students were recruited from a boarding middle school. Each participant was asked to respond to a detailed questionnaire on childhood maltreatment, from whom one blood sample was drawn via venous blood. Results In the overall sample there was no association between childhood maltreatment and peripheral serum inflammatory cytokines; (2) emotional abuse was significantly correlated with IL-1β only in girls (B = -0.16; 95% CI, -0.28~-0.03; p = 0.06); (3) in late adolescence, emotional abuse, emotional neglect, and childhood maltreatment had marked link with IL-8 (B = 0.39; 95%CI, 0.16~0.63; p = 0.01; B =0.20; 95% CI, 0.04~0.37; p = 0.08; B = 0.50; 95% CI, 0.18~0.82; p = 0.01, respectively). Conclusion These findings also strengthened an inference regarding the effects of childhood maltreatment on inflammation of students in late adolescence.
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Affiliation(s)
- Zhengge Jin
- Department of Maternal, Child & Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- Anhui Provincial Key Laboratory of Population Health & Aristogenics, Hefei, Anhui, China
| | - Shuqin Li
- Department of Maternal, Child & Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- Anhui Provincial Key Laboratory of Population Health & Aristogenics, Hefei, Anhui, China
| | - Ruoyu Li
- Department of Maternal, Child & Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- Anhui Provincial Key Laboratory of Population Health & Aristogenics, Hefei, Anhui, China
| | - Xianbing Song
- Department of Human Anatomy, Histology & Embryology, Anhui Medical College, Hefei, Anhui, China
| | - Shichen Zhang
- Department of Maternal, Child & Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- Anhui Provincial Key Laboratory of Population Health & Aristogenics, Hefei, Anhui, China
| | - Ying Sun
- Department of Maternal, Child & Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- Anhui Provincial Key Laboratory of Population Health & Aristogenics, Hefei, Anhui, China
| | - Fangbiao Tao
- Department of Maternal, Child & Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- Anhui Provincial Key Laboratory of Population Health & Aristogenics, Hefei, Anhui, China
| | - Yuhui Wan
- Department of Maternal, Child & Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- Anhui Provincial Key Laboratory of Population Health & Aristogenics, Hefei, Anhui, China
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Ernst MK, Evans ST, Techner JM, Rothbaum RM, Christensen LF, Onay UV, Biyashev D, Demczuk MM, Nguyen CV, Honda KS, McCormick TS, Tsoi LC, Gudjonsson JE, Cooper KD, Lu KQ. Vitamin D3 and deconvoluting a rash. JCI Insight 2023; 8:e163789. [PMID: 36692020 PMCID: PMC9977299 DOI: 10.1172/jci.insight.163789] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 11/30/2022] [Indexed: 01/25/2023] Open
Abstract
BACKGROUNDAdverse drug reactions are unpredictable immunologic events presenting frequent challenges to clinical management. Systemically administered cholecalciferol (vitamin D3) has immunomodulatory properties. In this randomized, double-blinded, placebo-controlled interventional trial of healthy human adults, we investigated the clinical and molecular immunomodulatory effects of a single high dose of oral vitamin D3 on an experimentally induced chemical rash.METHODSSkin inflammation was induced with topical nitrogen mustard (NM) in 28 participants. Participant-specific inflammatory responses to NM alone were characterized using clinical measures, serum studies, and skin tissue analysis over the next week. All participants underwent repeat NM exposure to the opposite arm and then received placebo or 200,000 IU cholecalciferol intervention. The complete rash reaction was followed by multi-omic analysis, clinical measures, and serum studies over 6 weeks.RESULTSCholecalciferol mitigated acute inflammation in all participants and achieved 6 weeks of durable responses. Integrative analysis of skin and blood identified an unexpected divergence in response severity to NM, corroborated by systemic neutrophilia and significant histopathologic and clinical differences. Multi-omic and pathway analyses revealed a 3-biomarker signature (CCL20, CCL2, CXCL8) unique to exaggerated responders that is suppressed by cholecalciferol and implicates IL-17 signaling involvement.CONCLUSIONHigh-dose systemic cholecalciferol may be an effective treatment for severe reactions to topical chemotherapy. Our findings have broad implications for cholecalciferol as an antiinflammatory intervention against the development of exaggerated immune responses.TRIAL REGISTRATIONclinicaltrials.gov (NCT02968446).FUNDINGNIH and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS; grants U01AR064144, U01AR071168, P30 AR075049, U54 AR079795, and P30 AR039750 (CWRU)).
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Affiliation(s)
- Madison K. Ernst
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Spencer T. Evans
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Jose-Marc Techner
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Robert M. Rothbaum
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Luisa F. Christensen
- Department of Dermatology, University Hospitals Cleveland Medical Center, Case Western Reserve University & Veterans Affairs Medical Center, Cleveland, Ohio, USA
| | - Ummiye Venus Onay
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Dauren Biyashev
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Michael M. Demczuk
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Cuong V. Nguyen
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Kord S. Honda
- Department of Dermatology, University Hospitals Cleveland Medical Center, Case Western Reserve University & Veterans Affairs Medical Center, Cleveland, Ohio, USA
| | - Thomas S. McCormick
- Department of Dermatology, University Hospitals Cleveland Medical Center, Case Western Reserve University & Veterans Affairs Medical Center, Cleveland, Ohio, USA
| | - Lam C. Tsoi
- Department of dermatology, University of Michigan, Ann Arbor, Michigan, USA
| | | | - Kevin D. Cooper
- Department of Dermatology, University Hospitals Cleveland Medical Center, Case Western Reserve University & Veterans Affairs Medical Center, Cleveland, Ohio, USA
| | - Kurt Q. Lu
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
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Cao XS, Zheng WQ, Hu ZD. Diagnostic value of soluble biomarkers for parapneumonic pleural effusion. Crit Rev Clin Lab Sci 2023; 60:233-247. [PMID: 36593742 DOI: 10.1080/10408363.2022.2158779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Parapneumonic pleural effusion (PPE) is a common complication in patients with pneumonia. Timely and accurate diagnosis of PPE is of great value for its management. Measurement of biomarkers in circulating and pleural fluid have the advantages of easy accessibility, short turn-around time, objectiveness and low cost and thus have utility for PPE diagnosis and stratification. To date, many biomarkers have been reported to be of value for the management of PPE. Here, we review the values of pleural fluid and circulating biomarkers for the diagnosis and stratification PPE. The biomarkers discussed are C-reactive protein, procalcitonin, presepsin, soluble triggering receptor expressed on myeloid cells 1, lipopolysaccharide-binding protein, inflammatory markers, serum amyloid A, soluble urokinase plasminogen activator receptor, matrix metalloproteinases, pentraxin-3 and cell-free DNA. We found that none of the available biomarkers has adequate performance for diagnosing and stratifying PPE. Therefore, further work is needed to identify and validate novel biomarkers, and their combinations, for the management of PPE.
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Affiliation(s)
- Xi-Shan Cao
- Department of Laboratory Medicine, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Wen-Qi Zheng
- Department of Laboratory Medicine, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Zhi-De Hu
- Department of Laboratory Medicine, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
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Stuqui B, Provazzi PJS, Lima MLD, Cabral ÁS, Leonel ECR, Candido NM, Taboga SR, da Silva MG, Lima FDO, Melli PPDS, Quintana SM, Calmon MDF, Rahal P. Condyloma acuminata: An evaluation of the immune response at cellular and molecular levels. PLoS One 2023; 18:e0284296. [PMID: 37053156 PMCID: PMC10101375 DOI: 10.1371/journal.pone.0284296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 03/28/2023] [Indexed: 04/14/2023] Open
Abstract
Condyloma acuminata (CA) is a benign proliferative disease mainly affecting in non-keratinized epithelia. Most cases of CA are caused by low-risk human papillomavirus (HPV), mainly HPV 6 and 11. The aim of the current study was to highlight the candidate genes and pathways associated with immune alterations in individuals who did not spontaneously eliminate the virus and, thus, develop genital warts. Paraffin-embedded condyloma samples (n = 56) were analyzed by immunohistochemistry using antibodies against CD1a, FOXP3, CD3, CD4, CD8, and IFN-γ. The immunomarkers were chosen based on the evaluation of the innate and adaptive immune pathways using qPCR analysis of 92 immune-related genes, applying a TaqMan Array Immune Response assay in HPV 6 or HPV 11 positive samples (n = 27). Gene expression analysis revealed 31 differentially expressed genes in CA lesions. Gene expression validation revealed upregulation of GZMB, IFNG, IL12B, and IL8 and downregulation of NFATC4 and IL7 in CA samples. Immunohistochemical analysis showed increased FOXP3, IFN-γ, CD1a, and CD4 expression in CA than in the control tissue samples. In contrast, CD3 and CD8 expression was decreased in CA lesion samples. Increased levels of pro-inflammatory cytokines in HPV-positive patients compared with HPV-negative patients seem to reflect the elevated immunogenicity of HPV-positive CA lesions. Host defense against HPV begins during the early stages of the innate immune response and is followed by activation of T lymphocytes, which are mainly represented by CD4+ and regulatory T cells. The low CD8+ T cell count in CA may contribute to this recurrent behavior. Additional studies are needed to elucidate the mechanism of host defense against HPV infection in CA.
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Affiliation(s)
- Bruna Stuqui
- Department of Biology, São Paulo State University, São José do Rio Preto, São Paulo, Brazil
| | | | | | - Ágata Silva Cabral
- Department of Biology, São Paulo State University, São José do Rio Preto, São Paulo, Brazil
| | | | - Natalia Maria Candido
- Department of Biology, São Paulo State University, São José do Rio Preto, São Paulo, Brazil
| | | | | | | | | | - Silvana Maria Quintana
- Department of Gynecology and Obstetrics, Ribeirāo Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | | | - Paula Rahal
- Department of Biology, São Paulo State University, São José do Rio Preto, São Paulo, Brazil
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Pawłowska M, Mila-Kierzenkowska C, Boraczyński T, Boraczyński M, Szewczyk-Golec K, Sutkowy P, Wesołowski R, Budek M, Woźniak A. The Influence of Ambient Temperature Changes on the Indicators of Inflammation and Oxidative Damage in Blood after Submaximal Exercise. Antioxidants (Basel) 2022; 11:2445. [PMID: 36552653 PMCID: PMC9774713 DOI: 10.3390/antiox11122445] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 12/05/2022] [Accepted: 12/09/2022] [Indexed: 12/14/2022] Open
Abstract
Physical activity has a positive effect on human health and well-being, but intense exercise can cause adverse changes in the organism, leading to the development of oxidative stress and inflammation. The aim of the study was to determine the effect of short-term cold water immersion (CWI) and a sauna bath as methods of postexercise regeneration on the indicators of inflammation and oxidative damage in the blood of healthy recreational athletes. Forty-five male volunteers divided into two groups: 'winter swimmers' who regularly use winter baths (n = 22, average age 43.2 ± 5.9 years) and 'novices' who had not used winter baths regularly before (n = 23, mean age 25 ± 4.8 years) participated in the study. The research was divided into two experiments, differing in the method of postexercise regeneration used, CWI (Experiment I) and a sauna bath (Experiment II). During Experiment I, the volunteers were subjected to a 30-min aerobic exercise, combined with a 20-min rest at room temperature (RT-REST) or a 20-min rest at room temperature with an initial 3-min 8 °C water bath (CWI-REST). During the Experiment II, the volunteers were subjected to the same aerobic exercise, followed by a RT-REST or a sauna bath (SAUNA-REST). The blood samples were taken before physical exercise (control), immediately after exercise and 20 min after completion of regeneration. The concentrations of selected indicators of inflammation, including interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 8 (IL-8), interleukin 10 (IL-10), transforming growth factor β1 (TGF-β1) and tumor necrosis factor α (TNF-α), as well as the activity of indicators of oxidative damage: α1-antitrypsin (AAT) and lysosomal enzymes, including arylsulfatase A (ASA), acid phosphatase (AcP) and cathepsin D (CTS D), were determined. CWI seems to be a more effective post-exercise regeneration method to reduce the inflammatory response compared to a sauna bath. A single sauna bath is associated with the risk of proteolytic tissue damage, but disturbances of cellular homeostasis are less pronounced in people who regularly use cold water baths than in those who are not adapted to thermal stress.
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Affiliation(s)
- Marta Pawłowska
- Department of Medical Biology and Biochemistry, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 87-100 Toruń, Poland
| | - Celestyna Mila-Kierzenkowska
- Department of Medical Biology and Biochemistry, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 87-100 Toruń, Poland
| | - Tomasz Boraczyński
- Department of Health Sciences, Olsztyn University College, 10-283 Olsztyn, Poland
| | - Michał Boraczyński
- Department of Health Sciences, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland
| | - Karolina Szewczyk-Golec
- Department of Medical Biology and Biochemistry, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 87-100 Toruń, Poland
| | - Paweł Sutkowy
- Department of Medical Biology and Biochemistry, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 87-100 Toruń, Poland
| | - Roland Wesołowski
- Department of Medical Biology and Biochemistry, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 87-100 Toruń, Poland
| | - Marlena Budek
- Department of Medical Biology and Biochemistry, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 87-100 Toruń, Poland
| | - Alina Woźniak
- Department of Medical Biology and Biochemistry, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 87-100 Toruń, Poland
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Boosting Lung Accumulation Of Gallium With Inhalable Nano-Embedded Microparticles For The Treatment Of Bacterial Pneumonia. Int J Pharm 2022; 629:122400. [DOI: 10.1016/j.ijpharm.2022.122400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 11/07/2022] [Accepted: 11/09/2022] [Indexed: 11/14/2022]
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Viksne RJ, Sumeraga G, Pilmane M. Characterization of Cytokines and Proliferation Marker Ki-67 in Chronic Rhinosinusitis with Recurring Nasal Polyps. Adv Respir Med 2022; 90:451-466. [PMID: 36285981 PMCID: PMC9717322 DOI: 10.3390/arm90050053] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 09/18/2022] [Accepted: 10/03/2022] [Indexed: 05/10/2025]
Abstract
BACKGROUND Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammation of the mucosa of the nose and paranasal sinuses with the presence of polyps, affecting between 2.7% and 4.4% of the population. Cytokine analysis has become important in research on inflammatory mechanisms in CRSwNP. Therefore, our aim is to investigate the complex appearance, relative distribution, and interlinks of IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, and Ki-67 in CRSwNP. METHODS Samples of nasal polyps were obtained from 19 patients with previously diagnosed CRSwNP and the recurrence of polyps after previous surgeries. The control group consisted of samples from 17 otherwise healthy individuals with isolated nasal septum deviations. Tissues were stained for previously mentioned cytokines and Ki-67 immunohistochemically. RESULTS Polyp samples showed an increased presence of cytokines in subepithelial connective tissue and a decreased appearance in epithelium when compared to controls. There were several very strong, strong, and moderate correlations among factors. CONCLUSIONS IL-6 strongly correlates with other cytokines as well as with the proliferation marker Ki-67, which suggests significant stimulation of this regulatory cytokine and its possible involvement in the pathogenesis of recurrent nasal polyps. IL-4, IL-7, IL-10, and IL-12 correlate with Ki-67, which suggests the possible involvement of these cytokines in tissue cell proliferation in the case of recurrent nasal polyps.
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Affiliation(s)
- Rudolfs Janis Viksne
- Department of Otorhinolaryngology, Riga Stradins University, Pilsonu Street 13, LV-1002 Riga, Latvia
- Daugavpils Regional Hospital, Vasarnicu Street 20, LV-5417 Daugavpils, Latvia
| | - Gunta Sumeraga
- Department of Otorhinolaryngology, Riga Stradins University, Pilsonu Street 13, LV-1002 Riga, Latvia
- Pauls Stradins Clinical University Hospital, Pilsonu Street 13, LV-1002 Riga, Latvia
| | - Mara Pilmane
- Institute of Anatomy and Anthropology, Riga Stradins University, Kronvalda Boulevard 9, LV-1010 Riga, Latvia
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Lan X, Wang C, Li W, Chao Z, Lao G, Wu K, Li G, Ning Y, Zhou Y. The association between overweight/obesity and poor cognitive function is mediated by inflammation in patients with major depressive disorder. J Affect Disord 2022; 313:118-125. [PMID: 35777493 DOI: 10.1016/j.jad.2022.06.073] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 05/27/2022] [Accepted: 06/23/2022] [Indexed: 01/10/2023]
Abstract
BACKGROUND Cognitive dysfunction is a common and core feature of major depressive disorder (MDD). Evidences exerted a potentially harmful role of obesity and higher peripheral levels of inflammation in cognitive function, but few studies have explored whether markers of peripheral inflammation might mediate the association between overweight/obesity and deficits in cognitive function. Our study aimed to examine the cognitive function in MDD patients and clarify the effects of overweight/obesity and inflammatory cytokines on cognitive dysfunction in this population. METHOD We used a cross-sectional design in this study. A total of 265 patients with MDD were enrolled and divided into underweight, normal weight and overweight/obese groups. The MATRICS Consensus Cognitive Battery (MCCB) was administered to measure the cognition. Plasma levels of nineteen cytokines were measured using high sensitivity multiplex bead-based assays. RESULTS We found overweight/obese MDD patients associated with higher plasma levels of tumor necrosis factor (TNF)-α, interleukin (IL)-8, and macrophage inflammatory protein (MIP)-1β and worse performance in speed of processing and working memory. The mediation analysis found higher levels of IL-8 (direct: β = -0.591 (95 % Confidence Interval (CI): -1.0 to -0.2), P = 0.002; indirect: β = 0.060 (95 % CI.: 0.0-0.2), P = 0.032) and TNF-α (direct: β = -0.589 (95 % CI.: -1.0 to -0.2), P = 0.002; indirect: β = 0.059 (95 % CI.: 0.1-0.2), P = 0.037) were associated with more deficits in speed of processing, and partially mediated the relationship between body mass index and speed of processing. CONCLUSION Our results suggest that elevated inflammation might be one biological mechanism underlying the link between higher body mass and deficits in processing speed in patients with MDD.
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Affiliation(s)
- Xiaofeng Lan
- The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China
| | - Chengyu Wang
- The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China
| | - Weicheng Li
- The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China
| | - Ziyuan Chao
- The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China
| | - Guohui Lao
- The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China
| | - Kai Wu
- The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China; School of Biomedical Sciences and Engineering, South china University of Technology, Guangzhou International Campus, Guangzhou, China
| | - Guixiang Li
- Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou, China
| | - Yuping Ning
- The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China; The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Yanling Zhou
- The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China.
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Joo MS, Choi KM, Kang G, Woo WS, Kim KH, Sohn MY, Son HJ, Han HJ, Choi HS, Kim DH, Park CI. Red sea bream interleukin (IL)-1β and IL-8 expression, subcellular localization, and antiviral activity against red sea bream iridovirus (RSIV). FISH & SHELLFISH IMMUNOLOGY 2022; 128:360-370. [PMID: 35868476 DOI: 10.1016/j.fsi.2022.07.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 07/08/2022] [Accepted: 07/13/2022] [Indexed: 06/15/2023]
Abstract
Interleukin-1 beta (IL-1β) is transcribed by monocytes, macrophages, and dendritic cells in response to activation of toll-like receptors (TLRs) by pathogen-associated molecular patterns (PAMPs) or cytokine signalling and causes a rapid inflammatory response to infection. IL-8, also known as chemokine C-X-C motif ligand (CXCL)-8, is regulated by IL-1β and affects the chemotaxis of macrophages and neutrophils upon pathogen infection. In healthy red sea bream, rsbIL-1β is most highly distributed in the liver, and rsbIL-8 is most highly distributed in the head kidney. In response to RSIV infection, rsbIL-1β and rsbIL-8 mRNA are significantly upregulated in the kidney and spleen. This may be because the primary infection targets of RSIV are the kidney and spleen. In the gills, both genes were significantly upregulated at 7 days after RSIV infection and may be accompanied by a cytokine storm. In the liver, both genes were significantly downregulated at most observation points, which may be because the immune cells such as macrophages and dendritic cells expressing rsbIL-1β or rsbIL-8 migrated to other tissues because the degree of RSIV infection was relatively low. Using a GFP fusion protein, it was confirmed that rsbIL-1β and rsbIL-8 were localized to the cytoplasm of Pagrus major fin (PMF) cells. RsbIL-1β overexpression induced the expression of interferon gamma (IFN-γ), myxovirus-resistance protein (Mx) 1, IL-8, IL-10, TNF-α, and MyD88, while rsbIL-8 overexpression induced the expression of IFN-γ, Mx1, rsbIL-1β and TNF-α. In addition, overexpression of both genes significantly reduced the genome copies of RSIV and significantly reduced the viral titers. Therefore, rsbIL-1β and rsbIL-8 in red sea bream play an antiviral role against RSIV through their normal signalling.
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Affiliation(s)
- Min-Soo Joo
- Department of Marine Biology & Aquaculture, Institute of Marine Industry, College of Marine Science, Gyeongsang National University, 455, Tongyeong, 650-160, Republic of Korea
| | - Kwang-Min Choi
- Department of Marine Biology & Aquaculture, Institute of Marine Industry, College of Marine Science, Gyeongsang National University, 455, Tongyeong, 650-160, Republic of Korea
| | - Gyoungsik Kang
- Department of Marine Biology & Aquaculture, Institute of Marine Industry, College of Marine Science, Gyeongsang National University, 455, Tongyeong, 650-160, Republic of Korea
| | - Won-Sik Woo
- Department of Marine Biology & Aquaculture, Institute of Marine Industry, College of Marine Science, Gyeongsang National University, 455, Tongyeong, 650-160, Republic of Korea
| | - Kyung-Ho Kim
- Department of Marine Biology & Aquaculture, Institute of Marine Industry, College of Marine Science, Gyeongsang National University, 455, Tongyeong, 650-160, Republic of Korea
| | - Min-Young Sohn
- Department of Marine Biology & Aquaculture, Institute of Marine Industry, College of Marine Science, Gyeongsang National University, 455, Tongyeong, 650-160, Republic of Korea
| | - Ha-Jeong Son
- Department of Marine Biology & Aquaculture, Institute of Marine Industry, College of Marine Science, Gyeongsang National University, 455, Tongyeong, 650-160, Republic of Korea
| | - Hyun-Ja Han
- Pathology Research Division, National Institute of Fisheries Science, 408-1 Sirang-ri, Gijang-up, Gijang-gun, Busan, 46083, Republic of Korea
| | - Hye-Sung Choi
- Pathology Research Division, National Institute of Fisheries Science, 408-1 Sirang-ri, Gijang-up, Gijang-gun, Busan, 46083, Republic of Korea
| | - Do-Hyung Kim
- Department of Aquatic Life Medicine, College of Fisheries Science, Pukyong National University, 45, Yongso-ro, Nam-Gu, Busan, Republic of Korea.
| | - Chan-Il Park
- Department of Marine Biology & Aquaculture, Institute of Marine Industry, College of Marine Science, Gyeongsang National University, 455, Tongyeong, 650-160, Republic of Korea.
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Upadhyay TK, Trivedi R, Khan F, Pandey P, Sharangi AB, Goel H, Saeed M, Park MN, Kim B. Potential Therapeutic Role of Mesenchymal-Derived Stem Cells as an Alternative Therapy to Combat COVID-19 through Cytokines Storm. Cells 2022; 11:2686. [PMID: 36078094 PMCID: PMC9455060 DOI: 10.3390/cells11172686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 08/20/2022] [Accepted: 08/25/2022] [Indexed: 01/08/2023] Open
Abstract
Medical health systems continue to be challenged due to newly emerging COVID-19, and there is an urgent need for alternative approaches for treatment. An increasing number of clinical observations indicate cytokine storms to be associated with COVID-19 severity and also to be a significant cause of death among COVID-19 patients. Cytokine storm involves the extensive proliferative and hyperactive activity of T and macrophage cells and the overproduction of pro-inflammatory cytokines. Stem cells are the type of cell having self-renewal properties and giving rise to differentiated cells. Currently, stem cell therapy is an exciting and promising therapeutic approach that can treat several diseases that were considered incurable in the past. It may be possible to develop novel methods to treat various diseases by identifying stem cells' growth and differentiation factors. Treatment with mesenchymal stem cells (MSCs) in medicine is anticipated to be highly effective. The present review article is organized to put forward the positive arguments and implications in support of mesenchymal stem cell therapy as an alternative therapy to cytokine storms, to combat COVID-19. Using the immunomodulatory potential of the MSCs, it is possible to fight against COVID-19 and counterbalance the cytokine storm.
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Affiliation(s)
- Tarun Kumar Upadhyay
- Department of Biotechnology, Parul Institute of Applied Sciences and Animal Cell Culture and Immunobiochemistry Lab, Centre of Research for Development, Parul University, Vadodara 391760, India
| | - Rashmi Trivedi
- Department of Biotechnology, Parul Institute of Applied Sciences and Animal Cell Culture and Immunobiochemistry Lab, Centre of Research for Development, Parul University, Vadodara 391760, India
| | - Fahad Khan
- Department of Biotechnology, Noida Institute of Engineering & Technology, Greater Noida 201306, India
| | - Pratibha Pandey
- Department of Biotechnology, Noida Institute of Engineering & Technology, Greater Noida 201306, India
| | - Amit Baran Sharangi
- Department of Plantation, Spices, Medicinal & Aromatic Crops, BCKV-Agricultural University, Mohanpur 741252, India
| | - Harsh Goel
- Department of Laboratory Oncology, All India Institute of Medical Sciences, New Delhi 110023, India
| | - Mohd Saeed
- Department of Biology, College of Sciences, University of Hail, Hail 34464, Saudi Arabia
| | - Moon Nyeo Park
- Department of Korean Medicine, Kyung Hee University, Seoul 05254, Korea
| | - Bonglee Kim
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea
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Effects of Periodontal Treatment on Levels of Proinflammatory Cytokines in Patients with Chronic Periodontitis: A Meta-Analysis. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:9349598. [PMID: 35928974 PMCID: PMC9345718 DOI: 10.1155/2022/9349598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 07/06/2022] [Accepted: 07/09/2022] [Indexed: 11/18/2022]
Abstract
Background During the progression of chronic periodontitis (CP), changes in the levels of inflammatory factors are detected in serum and gingival sulcus fluid (GCF). The aim of this meta-analysis was to systematically evaluate the effect of periodontal treatment on GCF and serum proinflammatory cytokines (IL-6, TNF-α, and IL-8) in patients with CP. Methods Literature searches were performed through PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang Database. Randomized controlled trials comparing cytokine levels in periodontal treatment (experimental group) and control group between 2015 and 2020 were included. Results There were a total of 13 studies included with 1220 patients. There were 630 cases in the experimental group and 590 cases in the control group. The meta-analysis showed that IL-6 levels in the GCF (SMD = −2.88, 95% CI (-3.68, -2.09), P < 0.001) and serum (SMD = −1.27, 95% CI (-1.72, -0.81), P < 0.001) were significantly lower in the experimental group compared with those before treatment. In addition, IL-8 levels in the GCF (SMD = −2.08, 95% CI (-3.40, -0.76), P < 0.001) and serum (SMD = −1.73, 95% CI (-2.76, -0.70), P < 0.001) were decreased after periodontal treatment, but more than that, a decrease was observed in TNF-α levels of GCF (SMD = −3.98, 95% CI (-5.23, -2.73), P < 0.001) and serum (SMD = −1.80, 95% CI (-3.16, -0.45), P < 0.001) after treatment. Conclusion After periodontal therapy, the proinflammatory cytokines in the GCF and serum of patients with CP were significantly decreased compared with those before treatment, and the efficacy was remarkable.
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Guo S, Zhang E, Zhang B, Liu Q, Meng Z, Li Z, Wang C, Gong Z, Wu Y. Identification of Key Non-coding RNAs and Transcription Factors in Calcific Aortic Valve Disease. Front Cardiovasc Med 2022; 9:826744. [PMID: 35845040 PMCID: PMC9276990 DOI: 10.3389/fcvm.2022.826744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 06/01/2022] [Indexed: 11/25/2022] Open
Abstract
Background Calcific aortic valve disease (CAVD) is one of the most frequently occurring valvular heart diseases among the aging population. Currently, there is no known pharmacological treatment available to delay or reverse CAVD progression. The regulation of gene expression could contribute to the initiation, progression, and treatment of CAVD. Non-coding RNAs (ncRNAs) and transcription factors play essential regulatory roles in gene expression in CAVD; thus, further research is urgently needed. Materials and Methods The gene-expression profiles of GSE51472 and GSE12644 were obtained from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) were identified in each dataset. A protein-protein-interaction (PPI) network of DEGs was then constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins database, and functional modules were analyzed with ClusterOne plugin in Cytoscape. Furthermore, Gene Ontology-functional annotation and Kyoto Encyclopedia of Genes and Genomes-pathway analysis were conducted for each functional module. Most crucially, ncRNAs and transcription factors acting on each functional module were separately identified using the RNAInter and TRRUST databases. The expression of predicted transcription factors and key genes was validated using GSE51472 and GSE12644. Furthermore, quantitative real-time PCR (qRT-PCR) experiments were performed to validate the differential expression of most promising candidates in human CAVD and control samples. Results Among 552 DEGs, 383 were upregulated and 169 were downregulated. In the PPI network, 15 functional modules involving 182 genes and proteins were identified. After hypergeometric testing, 45 ncRNAs and 33 transcription factors were obtained. Among the predicted transcription factors, CIITA, HIF1A, JUN, POU2F2, and STAT6 were differentially expressed in both the training and validation sets. In addition, we found that key genes, namely, CD2, CD86, CXCL8, FCGR3B, GZMB, ITGB2, LY86, MMP9, PPBP, and TYROBP were also differentially expressed in both the training and validation sets. Among the most promising candidates, differential expressions of ETS1, JUN, NFKB1, RELA, SP1, STAT1, ANCR, and LOC101927497 were identified via qRT-PCR experiments. Conclusion In this study, we identified functional modules with ncRNAs and transcription factors involved in CAVD pathogenesis. The current results suggest candidate molecules for further research on CAVD.
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Rogal J, Roosz J, Teufel C, Cipriano M, Xu R, Eisler W, Weiss M, Schenke‐Layland K, Loskill P. Autologous Human Immunocompetent White Adipose Tissue-on-Chip. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2022; 9:e2104451. [PMID: 35466539 PMCID: PMC9218765 DOI: 10.1002/advs.202104451] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 03/03/2022] [Indexed: 05/07/2023]
Abstract
Obesity and associated diseases, such as diabetes, have reached epidemic proportions globally. In this era of "diabesity", white adipose tissue (WAT) has become a target of high interest for therapeutic strategies. To gain insights into mechanisms of adipose (patho-)physiology, researchers traditionally relied on animal models. Leveraging Organ-on-Chip technology, a microphysiological in vitro model of human WAT is introduced: a tailored microfluidic platform featuring vasculature-like perfusion that integrates 3D tissues comprising all major WAT-associated cellular components (mature adipocytes, organotypic endothelial barriers, stromovascular cells including adipose tissue macrophages) in an autologous manner and recapitulates pivotal WAT functions, such as energy storage and mobilization as well as endocrine and immunomodulatory activities. A precisely controllable bottom-up approach enables the generation of a multitude of replicates per donor circumventing inter-donor variability issues and paving the way for personalized medicine. Moreover, it allows to adjust the model's degree of complexity via a flexible mix-and-match approach. This WAT-on-Chip system constitutes the first human-based, autologous, and immunocompetent in vitro adipose tissue model that recapitulates almost full tissue heterogeneity and can become a powerful tool for human-relevant research in the field of metabolism and its associated diseases as well as for compound testing and personalized- and precision medicine applications.
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Affiliation(s)
- Julia Rogal
- Department for Microphysiological Systems, Institute of Biomedical EngineeringEberhard Karls University TübingenÖsterbergstr. 3Tübingen72074Germany
- Fraunhofer Institute for Interfacial Engineering and Biotechnology IGBNobelstr. 12Stuttgart70569Germany
| | - Julia Roosz
- NMI Natural and Medical Sciences Institute at the University of TübingenMarkwiesenstr. 55Reutlingen72770Germany
| | - Claudia Teufel
- Department for Microphysiological Systems, Institute of Biomedical EngineeringEberhard Karls University TübingenÖsterbergstr. 3Tübingen72074Germany
| | - Madalena Cipriano
- Department for Microphysiological Systems, Institute of Biomedical EngineeringEberhard Karls University TübingenÖsterbergstr. 3Tübingen72074Germany
- 3R‐Center for In vitro Models and Alternatives to Animal TestingEberhard Karls University TübingenÖsterbergstr. 3Tübingen72074Germany
| | - Raylin Xu
- Fraunhofer Institute for Interfacial Engineering and Biotechnology IGBNobelstr. 12Stuttgart70569Germany
- Harvard Medical School (HMS)25 Shattuck StBostonMA02115USA
| | - Wiebke Eisler
- Clinic for PlasticReconstructiveHand and Burn SurgeryBG Trauma CenterEberhard Karls University TübingenSchnarrenbergstraße 95Tübingen72076Germany
| | - Martin Weiss
- NMI Natural and Medical Sciences Institute at the University of TübingenMarkwiesenstr. 55Reutlingen72770Germany
- Department of Women's HealthEberhard Karls University TübingenCalwerstrasse 7Tübingen72076Germany
| | - Katja Schenke‐Layland
- NMI Natural and Medical Sciences Institute at the University of TübingenMarkwiesenstr. 55Reutlingen72770Germany
- Department of Medicine/CardiologyCardiovascular Research LaboratoriesDavid Geffen School of Medicine at UCLA675 Charles E. Young Drive South, MRL 3645Los AngelesCA90095USA
- Cluster of Excellence iFIT (EXC2180) “Image‐Guided and Functionally Instructed Tumor Therapies”Eberhard Karls University TuebingenRöntgenweg 11Tuebingen72076Germany
- Department for Medical Technologies and Regenerative MedicineInstitute of Biomedical EngineeringEberhard Karls University TübingenSilcherstr. 7/1Tübingen72076Germany
| | - Peter Loskill
- Department for Microphysiological Systems, Institute of Biomedical EngineeringEberhard Karls University TübingenÖsterbergstr. 3Tübingen72074Germany
- NMI Natural and Medical Sciences Institute at the University of TübingenMarkwiesenstr. 55Reutlingen72770Germany
- 3R‐Center for In vitro Models and Alternatives to Animal TestingEberhard Karls University TübingenÖsterbergstr. 3Tübingen72074Germany
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Paul P, Kaul R, Abdellatif B, Arabi M, Upadhyay R, Saliba R, Sebah M, Chaari A. The Promising Role of Microbiome Therapy on Biomarkers of Inflammation and Oxidative Stress in Type 2 Diabetes: A Systematic and Narrative Review. Front Nutr 2022; 9:906243. [PMID: 35711547 PMCID: PMC9197462 DOI: 10.3389/fnut.2022.906243] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 04/08/2022] [Indexed: 12/12/2022] Open
Abstract
Background One in 10 adults suffer from type 2 diabetes (T2D). The role of the gut microbiome, its homeostasis, and dysbiosis has been investigated with success in the pathogenesis as well as treatment of T2D. There is an increasing volume of literature reporting interventions of pro-, pre-, and synbiotics on T2D patients. Methods Studies investigating the effect of pro-, pre-, and synbiotics on biomarkers of inflammation and oxidative stress in T2D populations were extracted from databases such as PubMed, Scopus, Web of Science, Embase, and Cochrane from inception to January 2022. Results From an initial screening of 5,984 hits, 47 clinical studies were included. Both statistically significant and non-significant results have been compiled, analyzed, and discussed. We have found various promising pro-, pre-, and synbiotic formulations. Of these, multistrain/multispecies probiotics are found to be more effective than monostrain interventions. Additionally, our findings show resistant dextrin to be the most promising prebiotic, followed closely by inulin and oligosaccharides. Finally, we report that synbiotics have shown excellent effect on markers of oxidative stress and antioxidant enzymes. We further discuss the role of metabolites in the resulting effects in biomarkers and ultimately pathogenesis of T2D, bring attention toward the ability of such nutraceuticals to have significant role in COVID-19 therapy, and finally discuss few ongoing clinical trials and prospects. Conclusion Current literature of pro-, pre- and synbiotic administration for T2D therapy is promising and shows many significant results with respect to most markers of inflammation and oxidative stress.
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Affiliation(s)
- Pradipta Paul
- Division of Medical Education, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
| | - Ridhima Kaul
- Division of Medical Education, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
| | - Basma Abdellatif
- Division of Medical Education, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
| | - Maryam Arabi
- Division of Premedical Education, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
| | - Rohit Upadhyay
- Department of Medicine—Nephrology and Hypertension, Tulane University, School of Medicine, New Orleans, LA, United States
| | - Reya Saliba
- Distributed eLibrary, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
| | - Majda Sebah
- Division of Premedical Education, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
| | - Ali Chaari
- Division of Premedical Education, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
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Lan C, Chen S, Jiang S, Lei H, Cai Z, Huang X. Different expression patterns of inflammatory cytokines induced by lipopolysaccharides from Escherichia coli or Porphyromonas gingivalis in human dental pulp stem cells. BMC Oral Health 2022; 22:121. [PMID: 35413908 PMCID: PMC9004173 DOI: 10.1186/s12903-022-02161-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 04/07/2022] [Indexed: 12/19/2022] Open
Abstract
Background Lipopolysaccharide (LPS) is one of the leading causes of pulpitis. The differences in establishing an in vitro pulpitis model by using different lipopolysaccharides (LPSs) are unknown. This study aimed to determine the discrepancy in the ability to induce the expression of inflammatory cytokines and the underlying mechanism between Escherichia coli (E. coli) and Porphyromonas gingivalis (P. gingivalis) LPSs in human dental pulp stem cells (hDPSCs).
Material and methods Quantitative real-time polymerase chain reaction (QRT-PCR) was used to evaluate the mRNA levels of inflammatory cytokines including IL-6, IL-8, COX-2, IL-1β, and TNF-α expressed by hDPSCs at each time point. ELISA was used to assess the interleukin-6 (IL-6) protein level. The role of toll-like receptors (TLR)2 and TLR4 in the inflammatory response in hDPSCs initiated by LPSs was assessed by QRT-PCR and flow cytometry. Results The E. coli LPS significantly enhanced the mRNA expression of inflammatory cytokines and the production of the IL-6 protein (p < 0.05) in hDPSCs. The peaks of all observed inflammation mediators’ expression in hDPSCs were reached 3–12 h after stimulation by 1 μg/mL E. coli LPS. E. coli LPS enhanced the TLR4 expression (p < 0.05) but not TLR2 in hDPSCs, whereas P. gingivalis LPS did not affect TLR2 or TLR4 expression in hDPSCs. The TLR4 inhibitor pretreatment significantly inhibited the gene expression of inflammatory cytokines upregulated by E. coli LPS (p < 0.05). Conclusion Under the condition of this study, E. coli LPS but not P. gingivalis LPS is effective in promoting the expression of inflammatory cytokines by hDPSCs. E. coli LPS increases the TLR4 expression in hDPSCs. P. gingivalis LPS has no effect on TLR2 or TLR4 expression in hDPSCs. Supplementary Information The online version contains supplementary material available at 10.1186/s12903-022-02161-x.
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Affiliation(s)
- Chunhua Lan
- Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Zhong Road, Fuzhou, 350002, China.,Institute of Stomatology & Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
| | - Shuai Chen
- Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Zhong Road, Fuzhou, 350002, China.,Institute of Stomatology & Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
| | - Shan Jiang
- Southern Medical University, Shenzhen Stomatology Hospital (Pingshan), Shenzhen, China
| | - Huaxiang Lei
- Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Zhong Road, Fuzhou, 350002, China.,Institute of Stomatology & Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
| | - Zhiyu Cai
- Department of Stomatology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Xiaojing Huang
- Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Zhong Road, Fuzhou, 350002, China. .,Institute of Stomatology & Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China.
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Soltani Khaboushan A, Yazdanpanah N, Rezaei N. Neuroinflammation and Proinflammatory Cytokines in Epileptogenesis. Mol Neurobiol 2022; 59:1724-1743. [PMID: 35015252 DOI: 10.1007/s12035-022-02725-6] [Citation(s) in RCA: 118] [Impact Index Per Article: 39.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 12/30/2021] [Indexed: 02/06/2023]
Abstract
Increasing evidence corroborates the fundamental role of neuroinflammation in the development of epilepsy. Proinflammatory cytokines (PICs) are crucial contributors to the inflammatory reactions in the brain. It is evidenced that epileptic seizures are associated with elevated levels of PICs, particularly interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), which underscores the impact of neuroinflammation and PICs on hyperexcitability of the brain and epileptogenesis. Since the pathophysiology of epilepsy is unknown, determining the possible roles of PICs in epileptogenesis could facilitate unraveling the pathophysiology of epilepsy. About one-third of epileptic patients are drug-resistant, and existing treatments only resolve symptoms and do not inhibit epileptogenesis; thus, treatment of epilepsy is still challenging. Accordingly, understanding the function of PICs in epilepsy could provide us with promising targets for the treatment of epilepsy, especially drug-resistant type. In this review, we outline the role of neuroinflammation and its primary mediators, including IL-1β, IL-1α, IL-6, IL-17, IL-18, TNF-α, and interferon-γ (IFN-γ) in the pathophysiology of epilepsy. Furthermore, we discuss the potential therapeutic targeting of PICs and cytokine receptors in the treatment of epilepsy.
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Affiliation(s)
- Alireza Soltani Khaboushan
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Niloufar Yazdanpanah
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
- Children's Medical Center Hospital, Dr. Qarib St, Keshavarz Blvd, 14194, Tehran, Iran.
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Liu H, Sun J, Li M, Cai W, Chen Y, Liu Y, Huang H, Xie Z, Zeng W, Xi L. Molecular Characteristics of Regional Chromoblastomycosis in Guangdong, China: Epidemiological, Clinical, Antifungal Susceptibility, and Serum Cytokine Profiles of 45 Cases. Front Cell Infect Microbiol 2022; 12:810604. [PMID: 35252030 PMCID: PMC8894709 DOI: 10.3389/fcimb.2022.810604] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Accepted: 01/24/2022] [Indexed: 11/20/2022] Open
Abstract
Chromoblastomycosis (CBM) is a chronic disease caused by several species of dematiaceous fungi. In this study, a regional collection of 45 CBM cases was conducted in Guangdong, China, a hyper-endemic area of CBM. Epidemiology findings indicated that the mean age of cases was 61.38 ± 11.20 years, long duration ranged from 3 months to 30 years, and the gender ratio of male to female was 4.6:1. Thirteen cases (29%) declared underlying diseases. Verrucous form was the most common clinical manifestation (n = 19, 42%). Forty-five corresponding clinical strains were isolated, and 28 of them (62%) were identified as F. monophora; the remaining 17 (38%) were identified as F. nubica through ITS rDNA sequence analysis. Antifungal susceptibility tests in vitro showed low MICs in azoles (PCZ 0.015–0.25 μg/ml, VCZ 0.015–0.5 μg/ml, and ITZ 0.03–0.5 μg/ml) and TRB (0.015–1 μg/ml). Itraconazole combined with terbinafine was the main therapeutic strategy used for 31 of 45 cases, and 68% (n = 21) of them improved or were cured. Cytokine profile assays indicated upregulation of IL-4, IL-7, IL-15, IL-11, and IL-17, while downregulation of IL-1RA, MIP-1β, IL-8, and IL-16 compared to healthy donors (p < 0.05). The abnormal cytokine profiles indicated impaired immune response to eliminate fungus in CBM cases, which probably contributed to the chronic duration of this disease. In conclusion, we investigated the molecular epidemiological, clinical, and laboratory characteristics of CBM in Guangdong, China, which may assist further clinical therapy, as well as fundamental pathogenesis studies of CBM.
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Affiliation(s)
- Hongfang Liu
- Dermatology Hospital, Southern Medical University, Guangzhou, China
- Guangdong Dermatology Hospital of Anhui Medical University, Guangzhou, China
| | - Jiufeng Sun
- Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China
| | - Minying Li
- Dermatology Hospital, Southern Medical University, Guangzhou, China
| | - Wenying Cai
- Sun Yat-sen Memorial Hospital of Zhongshan University, Guangzhou, China
| | - Yangxia Chen
- Dermatology Hospital, Southern Medical University, Guangzhou, China
| | - Yinghui Liu
- Dermatology Hospital, Southern Medical University, Guangzhou, China
| | - Huan Huang
- Dermatology Hospital, Southern Medical University, Guangzhou, China
| | - Zhenmou Xie
- Dermatology Hospital, Southern Medical University, Guangzhou, China
| | - Weiying Zeng
- Dermatology Hospital, Southern Medical University, Guangzhou, China
| | - Liyan Xi
- Dermatology Hospital, Southern Medical University, Guangzhou, China
- Sun Yat-sen Memorial Hospital of Zhongshan University, Guangzhou, China
- Department of Dermatology and Venerology, Guangzhou First People’s Hospital, Guangzhou, China
- *Correspondence: Liyan Xi,
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Skibinska M, Rajewska-Rager A, Dmitrzak-Weglarz M, Kapelski P, Lepczynska N, Kaczmarek M, Pawlak J. Interleukin-8 and tumor necrosis factor-alpha in youth with mood disorders-A longitudinal study. Front Psychiatry 2022; 13:964538. [PMID: 36032249 PMCID: PMC9403049 DOI: 10.3389/fpsyt.2022.964538] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 07/25/2022] [Indexed: 11/13/2022] Open
Abstract
Bipolar disorder (BD) is one of the most disabling psychiatric illnesses. Over half of BD patients experienced early onset of the disease, and in most cases, it begins with a depressed mood episode. Up to 50% of adolescents initially diagnosed with major depressive disorder (MDD) convert to bipolar spectrum disorder. Diagnostic tools or biomarkers to facilitate the prediction of diagnosis conversion from MDD to BD are still lacking. Our study aimed to find biomarkers of diagnosis conversion in young patients with mood disorders. We performed a 2-year follow-up study on 69 adolescent patients diagnosed with MDD or BD. The control group consisted of 31 healthy youths. We monitored diagnosis change from MDD to BD. Impulsiveness was assessed using Barratt Impulsiveness Scale (BIS-11) and defense mechanisms using Defense Style Questionnaire (DSQ-40). According to the immunological hypothesis of mood disorders, we investigated baseline cytokines levels either in depressive or hypomanic/manic episodes. We correlated interleukin 8 (IL-8) and Tumor Necrosis Factor-alpha (TNF-alpha) levels with clinical factors. We detected higher IL-8 and TNF-alpha in patients in hypomanic/manic compared to depressed episodes. We found correlations of cytokine levels with immature defense style. We did not discover predictors of diagnosis conversion from MDD to BD.
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Affiliation(s)
- Maria Skibinska
- Protein Biomarkers Unit, Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland.,Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland
| | | | | | - Pawel Kapelski
- Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland
| | - Natalia Lepczynska
- Department of Child and Adolescent Psychiatry, Poznan University of Medical Sciences, Poznan, Poland
| | - Mariusz Kaczmarek
- Department of Cancer Immunology, Poznan University of Medical Sciences, Poznan, Poland
| | - Joanna Pawlak
- Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland
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Zhu ZH, Song XY, Man LJ, Chen P, Tang Z, Li RH, Ji CF, Dai NB, Liu F, Wang J, Zhang J, Jia QF, Hui L. Comparisons of Serum Interleukin-8 Levels in Major Depressive Patients With Drug-Free Versus SSRIs Versus Healthy Controls. Front Psychiatry 2022; 13:858675. [PMID: 35492731 PMCID: PMC9046727 DOI: 10.3389/fpsyt.2022.858675] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 03/14/2022] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE The interleukin-8 (IL-8) has been reported to play an important role in depression, which might be modulated by the selective serotonin reuptake inhibitors (SSRIs). Thus, the aim of this study was to investigate serum IL-8 levels, depressive symptom, and their associations in drug-free MDD patients, MDD patients with SSRIs, and healthy controls (HCs). METHODS Fifty-seven drug-free MDD patients (male/female = 35/22, mean age: 39.24 years), 30 MDD patients with SSRIs (male/female = 11/19, mean age: 39.73 years), and 101 HCs (male/female = 52/49, mean age: 37.38 years) were recruited in this cross-sectional study. Serum IL-8 levels and depressive symptom were assessed using the Flow Cytometer and Hamilton Depression Scale (HAMD). The analysis of variance was used for the comparison between groups. The relationship between serum log10 IL-8 levels and HAMD score was analyzed by Pearson correlation. RESULTS Serum log10IL-8 levels were lower in all patients than HCs after controlling for covariates (F = 4.86, p = 0.03). There was significant difference in serum Log10IL-8 levels among three groups after controlling for covariates (F = 14.63, p < 0.001). Serum Log10IL-8 levels in drug-free patients were lower compared to HCs (F = 19.38, p < 0.001) or patients with SSRIs (F = 21.89, p < 0.001) after controlling for covariates. However, there was not difference in serum log10IL-8 levels between patients with SSRIs and HCs after controlling for covariates. Moreover, serum Log10IL-8 levels were negatively correlated with HAMD score in all patients (r = -0.37, p = 0.02). Also, serum Log10IL-8 levels were negatively correlated with HAMD score in drug-free patients (r = -0.74, p = 0.01), but not in patients with SSRIs. CONCLUSION Our data supported that the decline in serum IL-8 levels was association with depression. Moreover, the SSRIs might modulate increased serum IL-8 levels of depression.
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Affiliation(s)
- Zhen Hua Zhu
- Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow University, Suzhou, China
| | - Xiao Ying Song
- Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow University, Suzhou, China
| | - Li Juan Man
- Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow University, Suzhou, China
| | - Peng Chen
- Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow University, Suzhou, China
| | - Zhen Tang
- Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow University, Suzhou, China
| | - Rong Hua Li
- Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow University, Suzhou, China
| | - Cai Fang Ji
- Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow University, Suzhou, China
| | - Ning Bin Dai
- Suzhou Center for Disease Prevention and Control, Suzhou, China
| | - Fang Liu
- Suzhou Center for Disease Prevention and Control, Suzhou, China
| | - Jing Wang
- Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow University, Suzhou, China
| | - Jianping Zhang
- Department of Psychiatry, Weill Cornell Medical College, Cornell University, New York, NY, United States
| | - Qiu Fang Jia
- Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow University, Suzhou, China
| | - Li Hui
- Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Medical College of Soochow University, Suzhou, China
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Affiliation(s)
- Yong-Ku Kim
- Department of Psychiatry, Korea University College of Medicine, Korea University Ansan Hospital, Ansan city, Republic of Korea.
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Hasankhani A, Bahrami A, Sheybani N, Fatehi F, Abadeh R, Ghaem Maghami Farahani H, Bahreini Behzadi MR, Javanmard G, Isapour S, Khadem H, Barkema HW. Integrated Network Analysis to Identify Key Modules and Potential Hub Genes Involved in Bovine Respiratory Disease: A Systems Biology Approach. Front Genet 2021; 12:753839. [PMID: 34733317 PMCID: PMC8559434 DOI: 10.3389/fgene.2021.753839] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 09/28/2021] [Indexed: 12/11/2022] Open
Abstract
Background: Bovine respiratory disease (BRD) is the most common disease in the beef and dairy cattle industry. BRD is a multifactorial disease resulting from the interaction between environmental stressors and infectious agents. However, the molecular mechanisms underlying BRD are not fully understood yet. Therefore, this study aimed to use a systems biology approach to systematically evaluate this disorder to better understand the molecular mechanisms responsible for BRD. Methods: Previously published RNA-seq data from whole blood of 18 healthy and 25 BRD samples were downloaded from the Gene Expression Omnibus (GEO) and then analyzed. Next, two distinct methods of weighted gene coexpression network analysis (WGCNA), i.e., module-trait relationships (MTRs) and module preservation (MP) analysis were used to identify significant highly correlated modules with clinical traits of BRD and non-preserved modules between healthy and BRD samples, respectively. After identifying respective modules by the two mentioned methods of WGCNA, functional enrichment analysis was performed to extract the modules that are biologically related to BRD. Gene coexpression networks based on the hub genes from the candidate modules were then integrated with protein-protein interaction (PPI) networks to identify hub-hub genes and potential transcription factors (TFs). Results: Four significant highly correlated modules with clinical traits of BRD as well as 29 non-preserved modules were identified by MTRs and MP methods, respectively. Among them, two significant highly correlated modules (identified by MTRs) and six nonpreserved modules (identified by MP) were biologically associated with immune response, pulmonary inflammation, and pathogenesis of BRD. After aggregation of gene coexpression networks based on the hub genes with PPI networks, a total of 307 hub-hub genes were identified in the eight candidate modules. Interestingly, most of these hub-hub genes were reported to play an important role in the immune response and BRD pathogenesis. Among the eight candidate modules, the turquoise (identified by MTRs) and purple (identified by MP) modules were highly biologically enriched in BRD. Moreover, STAT1, STAT2, STAT3, IRF7, and IRF9 TFs were suggested to play an important role in the immune system during BRD by regulating the coexpressed genes of these modules. Additionally, a gene set containing several hub-hub genes was identified in the eight candidate modules, such as TLR2, TLR4, IL10, SOCS3, GZMB, ANXA1, ANXA5, PTEN, SGK1, IFI6, ISG15, MX1, MX2, OAS2, IFIH1, DDX58, DHX58, RSAD2, IFI44, IFI44L, EIF2AK2, ISG20, IFIT5, IFITM3, OAS1Y, HERC5, and PRF1, which are potentially critical during infection with agents of bovine respiratory disease complex (BRDC). Conclusion: This study not only helps us to better understand the molecular mechanisms responsible for BRD but also suggested eight candidate modules along with several promising hub-hub genes as diagnosis biomarkers and therapeutic targets for BRD.
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Affiliation(s)
- Aliakbar Hasankhani
- Department of Animal Science, College of Agriculture and Natural Resources, University of Tehran, Karaj, Iran
| | - Abolfazl Bahrami
- Department of Animal Science, College of Agriculture and Natural Resources, University of Tehran, Karaj, Iran
- Nuclear Agriculture Research School, Nuclear Science and Technology Research Institute, Karaj, Iran
| | - Negin Sheybani
- Department of Animal and Poultry Science, College of Aburaihan, University of Tehran, Tehran, Iran
| | - Farhang Fatehi
- Department of Animal Science, College of Agriculture and Natural Resources, University of Tehran, Karaj, Iran
| | - Roxana Abadeh
- Department of Animal Science, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | | | | | - Ghazaleh Javanmard
- Department of Animal Science, College of Agriculture and Natural Resources, University of Tehran, Karaj, Iran
| | - Sadegh Isapour
- Department of Animal Science, College of Agriculture and Natural Resources, University of Tehran, Karaj, Iran
| | - Hosein Khadem
- Department of Agronomy and Plant Breeding, University of Tehran, Karaj, Iran
| | - Herman W. Barkema
- Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada
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Lee SA, Liu F, Yun DY, Riordan SM, Tay ACY, Liu L, Lee CS, Zhang L. Campylobacter concisus upregulates PD-L1 mRNA expression in IFN-γ sensitized intestinal epithelial cells and induces cell death in esophageal epithelial cells. J Oral Microbiol 2021; 13:1978732. [PMID: 34552702 PMCID: PMC8451702 DOI: 10.1080/20002297.2021.1978732] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 08/20/2021] [Accepted: 09/06/2021] [Indexed: 12/23/2022] Open
Abstract
Introduction: Campylobacter concisus is an oral bacterium that is associated with inflammatory bowel disease (IBD) and Barrett's esophagus (BE). Programmed cell death ligand-1 (PD-L1) is an immune checkpoint protein that is used by tumor cells for immune evasion and has increased expression in patients with IBD and BE. We examined whether C. concisus upregulates PD-L1 expression in intestinal and esophageal epithelial cells. Methods: Human intestinal epithelial HT-29 cells and esophageal epithelial FLO-1 cells with and without interferon (IFN)-γ sensitization were incubated with C. concisus strains. The level of PD-L1 mRNA was quantified using quantitative real-time PCR. Cytokines were measured using Enzyme-Linked Immunosorbent Assay (ELISA). Apoptosis of HT-29 and FLO-1 cells were measured using caspase 3/7 assay. Results: We found that intestinal epithelial cells with IFN-γ sensitization incubated with C. concisus significantly upregulated PD-L1 expression and significantly increased the production of interleukin (IL)-8. Whereas, PD-L1 expression was significantly inhibited in IFN-γ sensitized FLO-1 cells incubated with C. concisus strains. Furthermore, FLO-1 cells with and without IFN-γ sensitization incubated with C. concisus strains both had significantly higher levels of cell death. Conclusion: C. concisushas the potential to cause damage to both intestinal and esophageal epithelial cells, however, with different pathogenic effects.
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Affiliation(s)
- Seul A Lee
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Fang Liu
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Doo Young Yun
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Stephen M Riordan
- Gastrointestinal and Liver Unit,Prince of Wales Hospital, University of New South Wales, Sydney, Australia
| | - Alfred Chin Yen Tay
- Helicobacter Research Laboratory, Marshall Centre for Infectious Diseases Research and Training, School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia
| | - Lu Liu
- School of Medical Sciences, University of New South Wales, Sydney, Australia
| | - Cheok Soon Lee
- School of Medicine, Western Sydney University, Sydney, Australia
- South Western Sydney Clinical School, University of New South Wales, Sydney, Australia
- Central Clinical School, University of Sydney, Sydney, Australia
- Department of Anatomical Pathology, Liverpool Hospital, Sydney, Australia
| | - Li Zhang
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
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Anti-Oxidative and Immune Regulatory Responses of THP-1 and PBMC to Pulsed EMF Are Field-Strength Dependent. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18189519. [PMID: 34574442 PMCID: PMC8471206 DOI: 10.3390/ijerph18189519] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 09/07/2021] [Accepted: 09/08/2021] [Indexed: 12/26/2022]
Abstract
Innate immune cells react to electromagnetic fields (EMF) by generating reactive oxygen species (ROS), crucial intracellular messengers. Discrepancies in applied parameters of EMF studies, e.g., flux densities, complicate direct comparison of downstream anti-oxidative responses and immune regulatory signaling. We therefore compared the impact of different EMF flux densities in human leukemic THP1 cells and peripheral blood mononuclear cells (PBMC) of healthy donors to additionally consider a potential disparate receptivity based on medical origin. ROS levels increased in THP1 cells stimulated with lipopolysaccharide (LPS) after one hour of EMF exposure. Moreover, weak EMF mitigated the depletion of the reducing agent NAD(P)H in THP1. Neither of these effects occurred in PBMC. Landscaping transcriptional responses to varied EMF revealed elevation of the anti-oxidative enzymes PRDX6 (2-fold) and DHCR24 (6-fold) in THP1, implying involvement in lipid metabolism. Furthermore, our study confirmed anti-inflammatory effects of EMF by 6-fold increased expression of IL10. Strikingly, THP1 responded to weak EMF, while PBMC were primarily affected by strong EMF, yet with severe cellular stress and enhanced rates of apoptosis, indicated by HSP70 and caspase 3 (CASP3). Taken together, our results emphasize an altered susceptibility of immune cells of different origin and associate EMF-related effects with anti-inflammatory signaling and lipid metabolism.
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