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Kien NT, Hoa NP, Tung HH, Van den Broeck K, Wens J. Health-Related Quality of Life Among Type 2 Diabetes Patients With Depressive Symptoms in Vietnam. J Diabetes Res 2025; 2025:6992121. [PMID: 40190409 PMCID: PMC11971502 DOI: 10.1155/jdr/6992121] [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: 05/06/2024] [Accepted: 02/28/2025] [Indexed: 04/09/2025] Open
Abstract
Background: This study investigates the impact of Type 2 diabetes mellitus (T2DM) and depressive symptoms on the health-related quality of life (HRQoL) among patients at the Agricultural General Hospital in Hanoi, Vietnam. The research explores the interconnections between chronic physical conditions and mental health within a resource-constrained healthcare environment. Methods: A cross-sectional survey was conducted with 516 T2DM patients using the SF-36 to assess HRQoL and the PHQ-9 to measure depressive symptoms. The study examined the prevalence of depressive symptoms and their correlation with various HRQoL components. Results: Among the participants, 45.2% exhibited depressive symptoms from mild to severe levels. Significant disparities in HRQoL scores were observed, particularly in physical composite and overall quality of life scores between T2DM with and without depressive symptoms. Statistical analysis highlighted that depressive symptoms significantly diminish HRQoL, with the PHQ-9 scores serving as a robust predictor. Conclusion: The findings underscore the critical need for integrated care approaches that include mental health support for T2DM patients. Routine screening for depressive symptoms should be a component of diabetes management protocols to improve overall patient outcomes. Further longitudinal research is needed to confirm these findings and develop effective interventions.
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Affiliation(s)
- Nguyen Tran Kien
- Family Medicine Department, Hanoi Medical University, Hanoi, Vietnam
- Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
| | - Nguyen Phuong Hoa
- Family Medicine Department, Hanoi Medical University, Hanoi, Vietnam
| | - Ha Huu Tung
- General Hospital of Agriculture, Hanoi, Vietnam
| | - Kris Van den Broeck
- Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
| | - Johan Wens
- Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
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2
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Jadhav KK, Daouk J, Kurkinen K, Kraav SL, Eriksson P, Tolmunen T, Kanninen KM. Blood cytokines in major depressive disorder in drug-naïve adolescents: A systematic review and meta-analysis. J Affect Disord 2025; 372:48-55. [PMID: 39603515 DOI: 10.1016/j.jad.2024.11.071] [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: 09/06/2024] [Revised: 11/01/2024] [Accepted: 11/23/2024] [Indexed: 11/29/2024]
Abstract
BACKGROUND Major depressive disorder (MDD) is the most common mental health problem worldwide. Increased levels of inflammation are associated with MDD, though this relationship has been suggested to be bidirectional. The first incidence of a depressive episode usually occurs during adolescence. Hence, examining depressed, drug-naïve adolescents is important to understand the role of inflammation in the pathophysiology of MDD. Cytokines might play a crucial role in inflammation associated with MDD. Therefore, this article aims to investigate the changes in the levels of peripheral blood cytokines in adolescents with MDD. METHODS We conducted a systematic review and meta-analysis to assess the changes in peripheral blood cytokines in drug-naïve adolescents (10-18 years) with MDD. A comprehensive search across four databases was performed to identify original research articles. Studies in which the diagnosis of MDD was set by semi-structured interview were included. RESULTS Of 2291 articles, 12 met the inclusion criteria for the review, with seven suitable for meta-analysis & including up to five studies per cytokine. The meta-analysis revealed significant associations between tumor necrosis factor (TNF)-α (n = 222, Hedge's g = 0.51, p <0.01) and MDD in adolescents compared to healthy individuals. However, other blood cytokines, including interleukin (IL)-1β, IL-4, IL-6, IL-8, and interferon (IFN)-γ, did not significantly correlate with MDD in adolescents. CONCLUSION TNF-α was significantly elevated in drug-naïve adolescents with MDD. To further understand the role of TNF-α in MDD, a thorough investigation is required, taking into account the diversity, subtypes, chronicity, and severity of MDD.
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Affiliation(s)
- Kaustubh Kishor Jadhav
- A. I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
| | - Joud Daouk
- A. I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
| | - Karoliina Kurkinen
- Institute of Clinical Medicine, Department of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
| | - Siiri-Liisi Kraav
- Department of Social Sciences, Faculty of Social Sciences and Business Studies, University of Eastern Finland, Kuopio, Finland
| | - Päivi Eriksson
- Business School, Faculty of Social Sciences and Business Studies, University of Eastern Finland, Kuopio, Finland
| | - Tommi Tolmunen
- Institute of Clinical Medicine, Department of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland; Kuopio University Hospital, Department of Adolescent Psychiatry, Kuopio, Finland
| | - Katja M Kanninen
- A. I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
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Amato S, Arnold A. A Data-Informed Mathematical Model of Microglial Cell Dynamics During Ischemic Stroke in the Middle Cerebral Artery. Bull Math Biol 2025; 87:31. [PMID: 39847151 DOI: 10.1007/s11538-025-01412-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 01/06/2025] [Indexed: 01/24/2025]
Abstract
Neuroinflammation immediately follows the onset of ischemic stroke in the middle cerebral artery. During this process, microglial cells are activated in and recruited to the penumbra. Microglial cells can be activated into two different phenotypes: M1, which can worsen brain injury; or M2, which can aid in long-term recovery. In this study, we contribute a summary of experimental data on microglial cell counts in the penumbra following ischemic stroke induced by middle cerebral artery occlusion (MCAO) in mice and compile available data sets into a single set suitable for time series analysis. Further, we formulate a mathematical model of microglial cells in the penumbra during ischemic stroke due to MCAO. Through use of global sensitivity analysis and Markov Chain Monte Carlo (MCMC)-based parameter estimation, we analyze the effects of the model parameters on the number of M1 and M2 cells in the penumbra and fit identifiable parameters to the compiled experimental data set. We utilize results from MCMC parameter estimation to ascertain uncertainty bounds and forward predictions for the number of M1 and M2 microglial cells over time. Results demonstrate the significance of parameters related to M1 and M2 activation on the number of M1 and M2 microglial cells. Simulations further suggest that potential outliers in the observed data may be omitted and forecast predictions suggest a lingering inflammatory response.
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Affiliation(s)
- Sara Amato
- Bioinformatics and Computational Biology Program, Worcester Polytechnic Institute, Worcester, MA, USA
| | - Andrea Arnold
- Bioinformatics and Computational Biology Program, Worcester Polytechnic Institute, Worcester, MA, USA.
- Department of Mathematical Sciences, Worcester Polytechnic Institute, Worcester, MA, USA.
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Feng LS, Wang YM, Liu H, Ning B, Yu HB, Li SL, Wang YT, Zhao MJ, Ma J. Hyperactivity in the Hypothalamic-Pituitary-Adrenal Axis: An Invisible Killer for Anxiety and/or Depression in Coronary Artherosclerotic Heart Disease. J Integr Neurosci 2024; 23:222. [PMID: 39735967 DOI: 10.31083/j.jin2312222] [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: 07/15/2024] [Revised: 09/20/2024] [Accepted: 09/26/2024] [Indexed: 12/31/2024] Open
Abstract
The coexistence of anxiety or depression with coronary heart disease (CHD) is a significant clinical challenge in cardiovascular medicine. Recent studies have indicated that hypothalamic-pituitary-adrenal (HPA) axis activity could be a promising focus in understanding and addressing the development of treatments for comorbid CHD and anxiety or depression. The HPA axis helps to regulate the levels of inflammatory factors, thereby reducing oxidative stress damage, promoting platelet activation, and stabilizing gut microbiota, which enhance the survival and regeneration of neurons, endothelial cells, and other cell types, leading to neuroprotective and cardioprotective benefits. This review addresses the relevance of the HPA axis to the cardiovascular and nervous systems, as well as the latest research advancements regarding its mechanisms of action. The discussion includes a detailed function of the HPA axis in regulating the processes mentioned. Above all, it summarizes the therapeutic potential of HPA axis function as a biomarker for coronary atherosclerotic heart disease combined with anxiety or depression.
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Affiliation(s)
- Lan-Shuan Feng
- First Clinical Medical College, Shaanxi University of Chinese Medicine, 712046 Xianyang, Shaanxi, China
| | - Yi-Ming Wang
- First Clinical Medical College, Shaanxi University of Chinese Medicine, 712046 Xianyang, Shaanxi, China
| | - Huan Liu
- First Clinical Medical College, Shaanxi University of Chinese Medicine, 712046 Xianyang, Shaanxi, China
- The Department of Traditional Chinese Medicine, the First Affiliated Hospital of the Air Force Military Medical University, 710038 Xi'an, Shaanxi, China
| | - Bo Ning
- First Clinical Medical College, Shaanxi University of Chinese Medicine, 712046 Xianyang, Shaanxi, China
| | - Hu-Bin Yu
- First Clinical Medical College, Shaanxi University of Chinese Medicine, 712046 Xianyang, Shaanxi, China
| | - Shi-Lin Li
- First Clinical Medical College, Shaanxi University of Chinese Medicine, 712046 Xianyang, Shaanxi, China
| | - Yu-Ting Wang
- First Clinical Medical College, Shaanxi University of Chinese Medicine, 712046 Xianyang, Shaanxi, China
- Department of Cardiology, Affiliated Hospital of Shaanxi University of Chinese Medicine, 712000 Xianyang, Shaanxi, China
| | - Ming-Jun Zhao
- First Clinical Medical College, Shaanxi University of Chinese Medicine, 712046 Xianyang, Shaanxi, China
- Department of Cardiology, Affiliated Hospital of Shaanxi University of Chinese Medicine, 712000 Xianyang, Shaanxi, China
| | - Jing Ma
- First Clinical Medical College, Shaanxi University of Chinese Medicine, 712046 Xianyang, Shaanxi, China
- The Department of Traditional Chinese Medicine, the First Affiliated Hospital of the Air Force Military Medical University, 710038 Xi'an, Shaanxi, China
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5
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Cavaillon JM, Chaudry IH. Facing stress and inflammation: From the cell to the planet. World J Exp Med 2024; 14:96422. [PMID: 39713080 PMCID: PMC11551703 DOI: 10.5493/wjem.v14.i4.96422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 08/27/2024] [Accepted: 09/19/2024] [Indexed: 10/31/2024] Open
Abstract
As identified in 1936 by Hans Selye, stress is shaping diseases through the induction of inflammation. But inflammation display some yin yang properties. On one hand inflammation is merging with the innate immune response aimed to fight infectious or sterile insults, on the other hand inflammation favors chronic physical or psychological disorders. Nature has equipped the cells, the organs, and the individuals with mediators and mechanisms that allow them to deal with stress, and even a good stress (eustress) has been associated with homeostasis. Likewise, societies and the planet are exposed to stressful settings, but wars and global warming suggest that the regulatory mechanisms are poorly efficient. In this review we list some inducers of the physiological stress, psychologic stress, societal stress, and planetary stress, and mention some of the great number of parameters which affect and modulate the response to stress and render it different from an individual to another, from the cellular level to the societal one. The cell, the organ, the individual, the society, and the planet share many stressors of which the consequences are extremely interconnected ending in the domino effect and the butterfly effect.
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Affiliation(s)
| | - Irshad H Chaudry
- Department of Surgery, University of Alabama Birmingham, Birmingham, AL 35294, United States
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Dani C, Tarchi L, Cassioli E, Rossi E, Merola GP, Ficola A, Cordasco VZ, Ricca V, Castellini G. A transdiagnostic and diagnostic-specific approach on inflammatory biomarkers in eating disorders: A meta-analysis and systematic review. Psychiatry Res 2024; 340:116115. [PMID: 39128168 DOI: 10.1016/j.psychres.2024.116115] [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: 04/16/2024] [Revised: 07/23/2024] [Accepted: 07/28/2024] [Indexed: 08/13/2024]
Abstract
Eating disorders (EDs) are severe mental illnesses with a multifactorial etiology and a chronic course. Among the biological factors related to pathogenesis and maintenance of EDs, inflammation acquired growing scientific interest. This study aimed to assess the inflammatory profile of EDs, focusing on anorexia nervosa, bulimia nervosa, and including for the first time binge eating disorder. A comprehensive research of existing literature identified 51 eligible studies for meta-analysis, comparing levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), osteoprotegerin (OPG), soluble receptor activator of nuclear factor kappa-B ligand (sRANKL), interleukin-1β (IL-1β), and interleukin-10 (IL-10) between patients with EDs and healthy controls (HCs). The systematic review explored other inflammatory biomarkers of interest, which did not meet the meta-analysis criteria. Results revealed significantly elevated levels of TNF-α, OPG, sRANKL, and IL-1β in patients with EDs compared to HCs. Additionally, the results highlighted the heterogeneity of inflammatory state among patients with EDs, emphasizing the need for further research into the association between inflammatory biomarkers and psychopathological correlates. This approach should transcend categorical diagnoses, enabling more precise subcategorizations of patients. Overall, this study contributed to the understanding of the inflammatory pathways involved in EDs, emphasizing potential implications for diagnosis, staging, and targeted interventions.
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Affiliation(s)
- Cristiano Dani
- Department of Health Sciences, University of Florence, Florence, Italy
| | - Livio Tarchi
- Department of Health Sciences, University of Florence, Florence, Italy
| | - Emanuele Cassioli
- Department of Health Sciences, University of Florence, Florence, Italy
| | - Eleonora Rossi
- Department of Health Sciences, University of Florence, Florence, Italy
| | | | - Arianna Ficola
- Department of Health Sciences, University of Florence, Florence, Italy
| | | | - Valdo Ricca
- Department of Health Sciences, University of Florence, Florence, Italy
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7
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Maldonado-García JL, Alvarez-Herrera S, Pérez-Sánchez G, Becerril-Villanueva E, Pavón L, Tesoro-Cruz E, Girón-Pérez MI, Hurtado-Alvarado G, Damián-Morales G, López-Santiago R, Moreno-Lafont MC. Concomitant Treatment with Doxycycline and Rifampicin in Balb/c Mice Infected with Brucella abortus 2308 Fails to Reduce Inflammation and Motor Disability. Pharmaceuticals (Basel) 2024; 17:638. [PMID: 38794208 PMCID: PMC11123987 DOI: 10.3390/ph17050638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 05/11/2024] [Accepted: 05/13/2024] [Indexed: 05/26/2024] Open
Abstract
Brucellosis is an infection widely distributed around the world, and in some countries it is considered a public health problem. Brucellosis causes insidious symptoms that make it difficult to diagnose. Infection can also trigger chronic pain and neuropsychiatric complications. Antibiotics are not always effective to eradicate infection, contributing to chronicity. We aimed to investigate the effects of antibiotic treatment on proinflammatory cytokines, neurotransmitters, corticosterone, and behavior in a murine model of infecrion of B. abortus strain 2308. Four study groups were created: (a) control; (b) antibiotic control; (c) infected with B. abortus 2308; and (d) infected and treated with rifampicin and doxycycline. We determined B. abortus 2308 colony-forming units (CFUs), the count of dendritic cells, and macrophages in the spleen; serum levels of cytokines and corticosterone; levels of serotonin, dopamine, epinephrine, and norepinephrine in the brain; and equilibrium, physical strength, anxiety, and hopelessness tests. The infected and treated mice group was compared with the control and infected mice to assess whether treatment is sufficient to recover neuroimmunoendocrine parameters. Our results showed that despite the treatment of brucellosis with rifampicin and doxycycline, antibiotic-treated mice showed a persistence of B. abortus 2308 CFUs, an increased count in macrophage number, and higher circulating levels of corticosterone. Furthermore, the levels of IL-12, IL-6, and TNF-α remained higher. We found a decrease in muscular strength and equilibrium concomitant to changes in neurotransmitters in the hippocampus, cerebellum, and frontal cortex. Our data suggest that the remaining bacterial load after antibiotic administration favors inflammatory, neurochemical, and behavioral alterations, partly explaining the widespread and paradoxical symptomatology experienced by patients with chronic brucellosis.
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Affiliation(s)
- José Luis Maldonado-García
- Laboratorio de Inmunología Celular, Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico; (J.L.M.-G.); (G.D.-M.); (R.L.-S.)
- Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04360, Mexico
| | - Samantha Alvarez-Herrera
- Laboratorio de Psicoinmunología, Dirección de Investigaciones en Neurociencias del Instituto Nacional de Psiquiatría Ramón de la Fuente, Mexico City 14370, Mexico; (S.A.-H.); (G.P.-S.); (E.B.-V.)
| | - Gilberto Pérez-Sánchez
- Laboratorio de Psicoinmunología, Dirección de Investigaciones en Neurociencias del Instituto Nacional de Psiquiatría Ramón de la Fuente, Mexico City 14370, Mexico; (S.A.-H.); (G.P.-S.); (E.B.-V.)
| | - Enrique Becerril-Villanueva
- Laboratorio de Psicoinmunología, Dirección de Investigaciones en Neurociencias del Instituto Nacional de Psiquiatría Ramón de la Fuente, Mexico City 14370, Mexico; (S.A.-H.); (G.P.-S.); (E.B.-V.)
| | - Lenin Pavón
- Laboratorio de Psicoinmunología, Dirección de Investigaciones en Neurociencias del Instituto Nacional de Psiquiatría Ramón de la Fuente, Mexico City 14370, Mexico; (S.A.-H.); (G.P.-S.); (E.B.-V.)
| | - Emiliano Tesoro-Cruz
- Unidad de Investigación Biomédica en Inmunología e Infectología, Hospital de Infectología, Centro Médico Nacional “La Raza”, IMSS, Mexico City 02990, Mexico;
| | | | - Gabriela Hurtado-Alvarado
- Departamento de Anatomía, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04360, Mexico;
| | - Gabriela Damián-Morales
- Laboratorio de Inmunología Celular, Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico; (J.L.M.-G.); (G.D.-M.); (R.L.-S.)
| | - Rubén López-Santiago
- Laboratorio de Inmunología Celular, Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico; (J.L.M.-G.); (G.D.-M.); (R.L.-S.)
| | - Martha C. Moreno-Lafont
- Laboratorio de Inmunología Celular, Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico; (J.L.M.-G.); (G.D.-M.); (R.L.-S.)
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8
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Windoloski KA, Janum S, Berg RMG, Olufsen MS. Characterization of differences in immune responses during bolus and continuous infusion endotoxin challenges using mathematical modelling. Exp Physiol 2024; 109:689-710. [PMID: 38466166 PMCID: PMC11061636 DOI: 10.1113/ep091552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 02/13/2024] [Indexed: 03/12/2024]
Abstract
Endotoxin administration is commonly used to study the inflammatory response, and though traditionally given as a bolus injection, it can be administered as a continuous infusion over multiple hours. Several studies hypothesize that the latter better represents the prolonged and pronounced inflammation observed in conditions like sepsis. Yet very few experimental studies have administered endotoxin using both strategies, leaving significant gaps in determining the underlying mechanisms responsible for their differing immune responses. We used mathematical modelling to analyse cytokine data from two studies administering a 2 ng kg-1 dose of endotoxin, one as a bolus and the other as a continuous infusion over 4 h. Using our model, we simulated the dynamics of mean and subject-specific cytokine responses as well as the response to long-term endotoxin administration. Cytokine measurements revealed that the bolus injection led to significantly higher peaks for interleukin (IL)-8, while IL-10 reaches higher peaks during continuous administration. Moreover, the peak timing of all measured cytokines occurred later with continuous infusion. We identified three model parameters that significantly differed between the two administration methods. Monocyte activation of IL-10 was greater during the continuous infusion, while tumour necrosis factor α $ {\alpha} $ and IL-8 recovery rates were faster for the bolus injection. This suggests that a continuous infusion elicits a stronger, longer-lasting systemic reaction through increased stimulation of monocyte anti-inflammatory mediator production and decreased recovery of pro-inflammatory catalysts. Furthermore, the continuous infusion model exhibited prolonged inflammation with recurrent peaks resolving within 2 days during long-term (20-32 h) endotoxin administration.
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Affiliation(s)
| | - Susanne Janum
- Frederiksberg and Bispebjerg HospitalsFrederiksbergDenmark
- Department of Biomedical SciencesUniversity of CopenhagenCopenhagenDenmark
| | - Ronan M. G. Berg
- Department of Biomedical SciencesUniversity of CopenhagenCopenhagenDenmark
- Department of Clinical Physiology and Nuclear Medicine and, Centre for Physical Activity ResearchCopenhagen University HospitalCopenhagenDenmark
- Neurovascular Research LaboratoryUniversity of South WalesPontypriddUK
| | - Mette S. Olufsen
- Department of MathematicsNorth Carolina State UniversityRaleighNorth CarolinaUSA
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Kouba BR, de Araujo Borba L, Borges de Souza P, Gil-Mohapel J, Rodrigues ALS. Role of Inflammatory Mechanisms in Major Depressive Disorder: From Etiology to Potential Pharmacological Targets. Cells 2024; 13:423. [PMID: 38474387 PMCID: PMC10931285 DOI: 10.3390/cells13050423] [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: 01/18/2024] [Revised: 02/20/2024] [Accepted: 02/26/2024] [Indexed: 03/14/2024] Open
Abstract
The involvement of central and peripheral inflammation in the pathogenesis and prognosis of major depressive disorder (MDD) has been demonstrated. The increase of pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, IL-18, and TNF-α) in individuals with depression may elicit neuroinflammatory processes and peripheral inflammation, mechanisms that, in turn, can contribute to gut microbiota dysbiosis. Together, neuroinflammation and gut dysbiosis induce alterations in tryptophan metabolism, culminating in decreased serotonin synthesis, impairments in neuroplasticity-related mechanisms, and glutamate-mediated excitotoxicity. This review aims to highlight the inflammatory mechanisms (neuroinflammation, peripheral inflammation, and gut dysbiosis) involved in the pathophysiology of MDD and to explore novel anti-inflammatory therapeutic approaches for this psychiatric disturbance. Several lines of evidence have indicated that in addition to antidepressants, physical exercise, probiotics, and nutraceuticals (agmatine, ascorbic acid, and vitamin D) possess anti-inflammatory effects that may contribute to their antidepressant properties. Further studies are necessary to explore the therapeutic benefits of these alternative therapies for MDD.
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Affiliation(s)
- Bruna R. Kouba
- Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil; (B.R.K.); (L.d.A.B.); (P.B.d.S.)
| | - Laura de Araujo Borba
- Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil; (B.R.K.); (L.d.A.B.); (P.B.d.S.)
| | - Pedro Borges de Souza
- Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil; (B.R.K.); (L.d.A.B.); (P.B.d.S.)
| | - Joana Gil-Mohapel
- Island Medical Program, Faculty of Medicine, University of British Columbia, Victoria, BC V8P 5C2, Canada
- Division of Medical Sciences, University of Victoria, Victoria, BC V8P 5C2, Canada
| | - Ana Lúcia S. Rodrigues
- Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil; (B.R.K.); (L.d.A.B.); (P.B.d.S.)
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10
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Mosili P, Mkhize BC, Sibiya NH, Ngubane PS, Khathi A. Review of the direct and indirect effects of hyperglycemia on the HPA axis in T2DM and the co-occurrence of depression. BMJ Open Diabetes Res Care 2024; 12:e003218. [PMID: 38413177 PMCID: PMC10900365 DOI: 10.1136/bmjdrc-2022-003218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 03/24/2023] [Indexed: 02/29/2024] Open
Abstract
Type 2 diabetes mellitus (T2DM) is characterized by persistent hyperglycemia which is further associated with hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Several studies have shown that HPA axis hyperactivity is heightened in the chronic hyperglycemic state with severe hyperglycemic events more likely to result in a depressive disorder. The HPA axis is also regulated by the immune system. Upon stress, under homeostatic conditions, the immune system is activated via the sympatho-adrenal-medullary axis resulting in an immune response which secretes proinflammatory cytokines. These cytokines aid in the activation of the HPA axis during stress. However, in T2DM, where there is persistent hyperglycemia, the immune system is dysregulated resulting in the elevated concentrations of these cytokines. The HPA axis, already activated by the hyperglycemia, is further activated by the cytokines which all contribute to a diagnosis of depression in patients with T2DM. However, the onset of T2DM is often preceded by pre-diabetes, a reversible state of moderate hyperglycemia and insulin resistance. Complications often seen in T2DM have been reported to begin in the pre-diabetic state. While the current management strategies have been shown to ameliorate the moderate hyperglycemic state and decrease the risk of developing T2DM, research is necessary for clinical studies to profile these direct effects of moderate hyperglycemia in pre-diabetes on the HPA axis and the indirect effects moderate hyperglycemia may have on the HPA axis by investigating the components of the immune system that play a role in regulating this pathway.
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Affiliation(s)
- Palesa Mosili
- Human Physiology, University of KwaZulu-Natal College of Health Sciences, Durban, KwaZulu-Natal, South Africa
| | - Bongeka Cassandra Mkhize
- Human Physiology, University of KwaZulu-Natal College of Health Sciences, Durban, KwaZulu-Natal, South Africa
| | | | - Phikelelani Sethu Ngubane
- Human Physiology, University of KwaZulu-Natal College of Health Sciences, Durban, KwaZulu-Natal, South Africa
| | - Andile Khathi
- Human Physiology, University of KwaZulu-Natal College of Health Sciences, Durban, KwaZulu-Natal, South Africa
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11
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Bonanno M, Papa D, Cerasa A, Maggio MG, Calabrò RS. Psycho-Neuroendocrinology in the Rehabilitation Field: Focus on the Complex Interplay between Stress and Pain. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:285. [PMID: 38399572 PMCID: PMC10889914 DOI: 10.3390/medicina60020285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 02/02/2024] [Accepted: 02/06/2024] [Indexed: 02/25/2024]
Abstract
Chronic stress and chronic pain share neuro-anatomical, endocrinological, and biological features. However, stress prepares the body for challenging situations or mitigates tissue damage, while pain is an unpleasant sensation due to nociceptive receptor stimulation. When pain is chronic, it might lead to an allostatic overload in the body and brain due to the chronic dysregulation of the physiological systems that are normally involved in adapting to environmental challenges. Managing stress and chronic pain (CP) in neurorehabilitation presents a significant challenge for healthcare professionals and researchers, as there is no definitive and effective solution for these issues. Patients suffering from neurological disorders often complain of CP, which significantly reduces their quality of life. The aim of this narrative review is to examine the correlation between stress and pain and their potential negative impact on the rehabilitation process. Moreover, we described the most relevant interventions used to manage stress and pain in the neurological population. In conclusion, this review sheds light on the connection between chronic stress and chronic pain and their impact on the neurorehabilitation pathway. Our results emphasize the need for tailored rehabilitation protocols to effectively manage pain, improve treatment adherence, and ensure comprehensive patient care.
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Affiliation(s)
- Mirjam Bonanno
- IRCCS Centro Neurolesi Bonino-Pulejo, 98124 Messina, Italy; (M.B.); (R.S.C.)
| | - Davide Papa
- International College of Osteopathic Medicine, 20092 Cinisello Balsamo, Italy;
| | - Antonio Cerasa
- S’Anna Institute, 88900 Crotone, Italy;
- Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), 98164 Messina, Italy
- Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
| | - Maria Grazia Maggio
- IRCCS Centro Neurolesi Bonino-Pulejo, 98124 Messina, Italy; (M.B.); (R.S.C.)
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Chen J, Zhao BC, Dai XY, Xu YR, Kang JX, Li JL. Drinking alkaline mineral water confers diarrhea resistance in maternally separated piglets by maintaining intestinal epithelial regeneration via the brain-microbe-gut axis. J Adv Res 2023; 52:29-43. [PMID: 36539076 PMCID: PMC10555785 DOI: 10.1016/j.jare.2022.12.008] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 11/29/2022] [Accepted: 12/14/2022] [Indexed: 12/23/2022] Open
Abstract
INTRODUCTION Diarrhea has the fourth-highest mortality rate of all diseases and causes a large number of infant deaths each year. The maternally separated (MS) piglet (newly weaned piglet) is an excellent model to investigate the treatment of diarrhea in infants. Drinking alkaline mineral water has the potential to be therapeutic in gastrointestinal disorders, particularly diarrhea, but the supporting evidence from system studies and the mechanisms involved have yet to be reported. OBJECTIVES This study aims to determine whether drinking alkaline mineral water confers diarrhea resistance in MS piglets under weaning stress and what the fundamental mechanisms involved are. METHODS MS piglets were used to create a stress-induced intestinal disorder-diarrhea susceptibility model. A total of 240 MS piglets were randomly divided into two groups (6 pens/group and 20 piglets/pen). IPEC-J2 cell line was used for in vitro evaluation. An alkaline mineral complex (AMC) water was employed, and its effect on the hypothalamus-pituitary-adrenocortical (HPA) axis, gut microbes, gut morphology, and intestinal epithelial cell (IEC) proliferation and differentiation were investigated using a variety of experimental methodology. RESULTS AMC water reduced diarrhea rate in MS piglets by inhibiting the HPA axis, ameliorating gut microbiota structure, and stimulating IEC proliferation and differentiation. Apparently, the brain-microbe-gut axis is linked with AMC water conferring diarrhea resistance in piglets. Mechanistically, AMC water decreased stress hormones (COR and Hpt) secretion by suppressing HPA axis, which then increased the abundance of beneficial gut microbes; accordingly, maintained the proliferation of IEC and promoted the differentiation of intestinal stem cells (ISC) into goblet cell and Paneth cell by activating the Wnt/β-catenin signaling pathway. In the absence of gut microbiota (in vitro), AMC activated the LPS-induced Wnt/β-catenin signaling inhibition in IPEC-J2 cells and significantly increased the number of Lgr5 + cells, whereas had no effect on IPEC-J2 differentiation. CONCLUSION Drinking alkaline mineral water confers diarrhea resistance in MS piglets by maintaining intestinal epithelial regeneration via the brain-microbe-gut axis; thus, this study provides a potential prevention strategy for young mammals at risk of diarrhea.
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Affiliation(s)
- Jian Chen
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China
| | - Bi-Chen Zhao
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China
| | - Xue-Yan Dai
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China
| | - Ya-Ru Xu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China
| | - Jian-Xun Kang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China
| | - Jin-Long Li
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin 150030, PR China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin 150030, PR China.
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Chen J, Xu XW, Kang JX, Zhao BC, Xu YR, Li JL. Metasilicate-based alkaline mineral water confers diarrhea resistance in maternally separated piglets via the microbiota-gut interaction. Pharmacol Res 2023; 187:106580. [PMID: 36436708 DOI: 10.1016/j.phrs.2022.106580] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/19/2022] [Accepted: 11/23/2022] [Indexed: 11/26/2022]
Abstract
Stress or stress-induced intestinal disturbances, especially diarrhea, are the main triggers for inflammatory bowel disease and irritable bowel syndrome. Diarrhea and intestinal inflammatory disease afflict patients around the world, and it has become a huge burden on the global health care system. Drinking sodium metasilicate-based alkaline mineral water (SM-based AMW) exerts a potential therapeutic effect in gastrointestinal disorders, including gut inflammation, and diarrhea, but the supportive evidence on animal studies and mechanism involved remain unreported. The maternally separated (MS) piglet (Newly weaned piglet) is an excellent model to investigate the treatment of diarrhea in infant. This study aims to determine whether drinking SM-based AMW confers diarrhea resistance in maternally separated (MS) piglets under weaning stress and what the underlying mechanisms are involved. 240 newly weaned piglets were randomly divided into the Control group and the sodium metasilicate pentahydrate (SMP) group. A decreased diarrhea incidence was observed in SMP treatment piglets. The intestine injury and activated stress hormones (COR and ACTH) induced by weaning was alleviated by SM-based AMW. This may be related to the improvement of intestinal microflora structure and function by SMP, especially the increase of s_copri abundance. Meanwhile, SMP maintained the integrity of the duodenal mucus barrier in MS piglets. Importantly, by targeting NF-κB inhibition via the microbiota-gut interaction, SM-based AMW alleviated intestinal inflammation, maintained fluid homeostasis by modulating aquaporins and fluid transporter expression, and enhanced barrier integrity by suppressing MLCK/p-MLC signaling. Therefore, drinking metasilicate-based alkaline mineral water confers diarrhea resistance in MS piglets via the microbiota-gut interaction.
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Affiliation(s)
- Jian Chen
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China
| | - Xiang-Wen Xu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China
| | - Jian-Xun Kang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China
| | - Bi-Chen Zhao
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China
| | - Ya-Ru Xu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China
| | - Jin-Long Li
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin 150030, PR China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin 150030, PR China.
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14
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Walker JJ, Romanò N. Fast dynamics in the HPA axis: Insight from mathematical and experimental studies. CURRENT OPINION IN ENDOCRINE AND METABOLIC RESEARCH 2022; 27:100403. [PMID: 36632146 PMCID: PMC9823091 DOI: 10.1016/j.coemr.2022.100403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
The activity of the hypothalamic-pituitary-adrenal (HPA) axis is characterised by complex dynamics spanning several timescales. This ranges from slow circadian rhythms in blood hormone concentration to faster ultradian pulses of hormone secretion and even more rapid oscillations in electrical and calcium activity in neuroendocrine cells of the hypothalamus and pituitary gland. Here, we focus on the system's oscillations on the short timescale. We highlight some of the mathematical modelling and experimental work that has been carried out to characterise the mechanisms regulating this highly dynamic mode of neuroendocrine signalling and discuss some future directions that may be explored to enhance understanding of HPA function.
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Affiliation(s)
- Jamie J. Walker
- Department of Mathematics and Statistics, Faculty of Environment, Science and Economy, University of Exeter, UK,Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, UK,Corresponding author: Walker, Jamie J
| | - Nicola Romanò
- Centre for Discovery Brain Sciences, University of Edinburgh, UK,Corresponding author: Romanò, Nicola twitter icon
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15
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Parker C, Nelson E, Zhang T. VeVaPy, a Python Platform for Efficient Verification and Validation of Systems Biology Models with Demonstrations Using Hypothalamic-Pituitary-Adrenal Axis Models. ENTROPY (BASEL, SWITZERLAND) 2022; 24:1747. [PMID: 36554152 PMCID: PMC9777964 DOI: 10.3390/e24121747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 11/21/2022] [Accepted: 11/24/2022] [Indexed: 06/17/2023]
Abstract
In order for mathematical models to make credible contributions, it is essential for them to be verified and validated. Currently, verification and validation (V&V) of these models does not meet the expectations of the system biology and systems pharmacology communities. Partially as a result of this shortfall, systemic V&V of existing models currently requires a lot of time and effort. In order to facilitate systemic V&V of chosen hypothalamic-pituitary-adrenal (HPA) axis models, we have developed a computational framework named VeVaPy-taking care to follow the recommended best practices regarding the development of mathematical models. VeVaPy includes four functional modules coded in Python, and the source code is publicly available. We demonstrate that VeVaPy can help us efficiently verify and validate the five HPA axis models we have chosen. Supplied with new and independent data, VeVaPy outputs objective V&V benchmarks for each model. We believe that VeVaPy will help future researchers with basic modeling and programming experience to efficiently verify and validate mathematical models from the fields of systems biology and systems pharmacology.
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Affiliation(s)
- Christopher Parker
- Department of Pharmacology & Systems Physiology, College of Medicine, University of Cincinnati, Cincinnati, OH 45221, USA
| | - Erik Nelson
- Department of Psychiatry & Behavioral Neuroscience, College of Medicine, University of Cincinnati, Cincinnati, OH 45221, USA
| | - Tongli Zhang
- Department of Pharmacology & Systems Physiology, College of Medicine, University of Cincinnati, Cincinnati, OH 45221, USA
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16
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Fong TCT, Ho RTH, Yau JCY. Longitudinal associations between salivary cortisol to C-reactive protein ratios and psychological well-being in Chinese adults. Psychoneuroendocrinology 2022; 143:105824. [PMID: 35689984 DOI: 10.1016/j.psyneuen.2022.105824] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 06/01/2022] [Accepted: 06/02/2022] [Indexed: 11/17/2022]
Abstract
BACKGROUND Salivary C-reactive protein (CRP) could be a viable biomarker of inflammation and has been associated with stress outcomes. The hypothalamic-pituitary-adrenal axis can modulate stress-related inflammation. This study aimed to evaluate the interaction effects of immune-endocrine markers on psychological outcomes. METHODS The study participants were 52 healthy Chinese adults who collected 10 saliva samples over 2 consecutive days at baseline. The participants completed validated measures on anxiety, depression, positive affect, and sleep disturbance at baseline and 1 month later. The stability and diurnal patterns of salivary cortisol and CRP were investigated via paired t-tests and repeated-measures analyses of variance. Regression analysis was used to examine the longitudinal associations between immune-endocrine markers and their interactions (cortisol [Cort]: morning CRP [CRPmorn] and Cort:CRPeven) and psychological measures. RESULTS Salivary cortisol and CRP displayed satisfactory stability over 2 consecutive days and diurnal patterns of abrupt and gradual decline during the day, respectively. Controlling for baseline psychological measures and confounding variables, Cortmorn and diurnal cortisol slope was significantly and negatively associated with anxiety symptoms and positive affect 1 month later, respectively. Cort:CRPeven and Cort:CRPmorn was significantly and positively associated with depressive symptoms and sleep disturbance 1 month later, respectively. CONCLUSION These findings offer initial support for the prognostic utility of salivary cortisol and CRP and their balance as determinants of psychological health in healthy adults.
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Affiliation(s)
- Ted C T Fong
- Centre on Behavioral Health, The University of Hong Kong, Hong Kong
| | - Rainbow T H Ho
- Centre on Behavioral Health, The University of Hong Kong, Hong Kong; Dept of Social Work & Social Administration, The University of Hong Kong, Hong Kong.
| | - Joshua C Y Yau
- Centre on Behavioral Health, The University of Hong Kong, Hong Kong
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17
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Zavala E. Misaligned hormonal rhythmicity: Mechanisms of origin and their clinical significance. J Neuroendocrinol 2022; 34:e13144. [PMID: 35514212 PMCID: PMC9286602 DOI: 10.1111/jne.13144] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 03/29/2022] [Accepted: 04/16/2022] [Indexed: 12/05/2022]
Abstract
Rhythmic hormonal secretion is key for sustaining health. While a central pacemaker in the hypothalamus is the main driver of circadian periodicity, many hormones oscillate with different frequencies and amplitudes. These rhythms carry information about healthy physiological functions, while at the same time they must be able to respond to external cues and maintain their robustness against severe perturbations. Since endocrine disruptions can lead to hormonal misalignment and disease, understanding the clinical significance of these rhythms can help support diagnosis and disease management. While the misalignment of dynamic hormone profiles can be quantitatively analysed though statistical and computational techniques, mathematical modelling can provide fundamental understanding about the mechanisms underpinning endocrine rhythms, particularly around the question of what makes them robust to some perturbations but fragile to others. In this study, I will review the key challenges of understanding hormonal rhythm misalignment from a mathematical perspective, including their causes and clinical significance. By reviewing modelling examples of coupled endocrine axes, I will address the question of how perturbations in one endocrine axis propagate to another, leading to the more complex issue of disentangling the contribution of each endocrine system to a robust dynamic environment.
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Affiliation(s)
- Eder Zavala
- Centre for Systems Modelling & Quantitative BiomedicineUniversity of BirminghamEdgbastonUK
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18
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Daniels J, Aldous A, Pyra M, Xia Y, Juzumaite M, Jais M, Simmens S, Murphy K, Taylor TN, Kassaye S, Benning L, Cohen MH, Weber KM, Ghosh M. Lifetime sexual violence exposure in women compromises systemic innate immune mediators associated with HIV pathogenesis: A cross-sectional analysis. WOMEN'S HEALTH (LONDON, ENGLAND) 2022; 18:17455057221099486. [PMID: 35579000 PMCID: PMC9118419 DOI: 10.1177/17455057221099486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVES Violence and HIV/AIDS syndemic highly prevalent among women impairs HIV prevention efforts. Prolonged exposure to violence results in physical trauma and psychological distress. Building on previous findings regarding genital immune dysregulation following sexual abuse exposure, we investigate here whether systemic changes occur as well. METHODS Using the Women's Interagency HIV Study repository, 77 women were stratified by HIV serostatus and categorized into four subgroups: (1) no sexual abuse history and lower depression score (Control); (2) no sexual abuse history but higher depression score (Depression); (3) high sexual abuse exposure and lower depression score (Abuse); (4) high sexual abuse exposure and higher depression score (Abuse + Depression). Inflammation-associated immune biomarkers (TNF-α, IL-6, IL-1α, IL-1β, TGF-β, MIP-3α, IP-10, MCP-1, and Cathepsin-B) and anti-inflammatory/anti-HIV biomarkers (Secretory leukocyte protease inhibitor, Elafin, human beta-defensin-2 (HBD-2), alpha-defensins 1-3, Thrombospondin, Serpin-A1, and Cystatin-C) were measured in plasma using enzyme-linked immunosorbent assay. Within each HIV serostatus, differences in biomarker levels between subgroups were evaluated with Kruskal-Wallis and Dunn's test with Bonferroni correction. Spearman correlations between biomarkers were assessed for each subgroup. RESULTS Compared to the Control and Depression groups, Abuse + Depression was associated with significantly higher levels of chemokines MIP-3α and IP-10 (p < 0.01) and lower levels of inflammatory cytokine IL-1β (p < 0.01) in the HIV-uninfected population. Human beta-defensin-2 was lowest in the Abuse + Depression group (p < 0.05 versus Depression). By contrast, among HIV-infected, Abuse and Abuse + Depression were associated with lower levels of MIP-3α (p < 0.05 versus Control) and IP-10 (p < 0.05, Abuse versus Control). Inflammatory cytokine IL-6 was higher in both Abuse groups (p < 0.05 versus Control), while Elafin was lowest in the Abuse + Depression group (p < 0.01 versus Depression). CONCLUSION We report compromised plasma immune responses that parallel previous findings in the genital mucosa, based on sexual abuse and HIV status. Systemic biomarkers may indicate trauma exposure and impact risk of HIV acquisition/transmission.
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Affiliation(s)
- Jason Daniels
- Department of Epidemiology, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA
| | - Annette Aldous
- Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA
| | - Maria Pyra
- The Chicago Center for HIV Elimination, The University of Chicago, Chicago, IL, USA
| | - Yu Xia
- Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA
| | - Monika Juzumaite
- Department of Epidemiology, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA
| | - Mariel Jais
- Department of Epidemiology, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA
| | - Samuel Simmens
- Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA
| | - Kerry Murphy
- Albert Einstein College of Medicine—Montefiore Medical Center, Bronx, NY, USA
| | - Tonya N Taylor
- SUNY Downstate Medical Center, The State University of New York, Brooklyn, NY, USA
| | - Seble Kassaye
- Georgetown University Medical Center, Washington, DC, USA
| | - Lorie Benning
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Mardge H Cohen
- Cook County Health and Hospitals System, Hektoen Institute of Medicine, Chicago, IL, USA
| | - Kathleen M Weber
- Cook County Health and Hospitals System, Hektoen Institute of Medicine, Chicago, IL, USA
| | - Mimi Ghosh
- Department of Epidemiology, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA,Mimi Ghosh, Department of Epidemiology, Milken Institute School of Public Health, The George Washington University, Washington, DC 20052, USA.
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Galvis D, Zavala E, Walker JJ, Upton T, Lightman SL, Angelini GD, Evans J, Rogers CA, Phillips K, Gibbison B. Modelling the dynamic interaction of systemic inflammation and the hypothalamic-pituitary-adrenal (HPA) axis during and after cardiac surgery. J R Soc Interface 2022; 19:20210925. [PMID: 35472267 PMCID: PMC9042572 DOI: 10.1098/rsif.2021.0925] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Major surgery and critical illness produce a potentially life-threatening systemic inflammatory response. The hypothalamic-pituitary-adrenal (HPA) axis is one of the key physiological systems that counterbalances this systemic inflammation through changes in adrenocorticotrophic hormone (ACTH) and cortisol. These hormones normally exhibit highly correlated ultradian pulsatility with an amplitude modulated by circadian processes. However, these dynamics are disrupted by major surgery and critical illness. In this work, we characterize the inflammatory, ACTH and cortisol responses of patients undergoing cardiac surgery and show that the HPA axis response can be classified into one of three phenotypes: single-pulse, two-pulse and multiple-pulse dynamics. We develop a mathematical model of cortisol secretion and metabolism that predicts the physiological mechanisms responsible for these different phenotypes. We show that the effects of inflammatory mediators are important only in the single-pulse pattern in which normal pulsatility is lost-suggesting that this phenotype could be indicative of the greatest inflammatory response. Investigating whether and how these phenotypes are correlated with clinical outcomes will be critical to patient prognosis and designing interventions to improve recovery.
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Affiliation(s)
- Daniel Galvis
- Centre for Systems Modelling and Quantitative Biomedicine (SMQB), University of Birmingham, Edgbaston B15 2TT, UK
| | - Eder Zavala
- Centre for Systems Modelling and Quantitative Biomedicine (SMQB), University of Birmingham, Edgbaston B15 2TT, UK
| | - Jamie J Walker
- Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol BS1 3NY, UK.,College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter EX4 4QD, UK
| | - Thomas Upton
- Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol BS1 3NY, UK
| | - Stafford L Lightman
- Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol BS1 3NY, UK
| | - Gianni D Angelini
- Bristol Heart Institute, Bristol Medical School, University of Bristol, Bristol BS1 3NY, UK
| | - Jon Evans
- Bristol Trials Centre, Bristol Medical School, University of Bristol, Bristol BS2 8HW, UK
| | - Chris A Rogers
- Bristol Trials Centre, Bristol Medical School, University of Bristol, Bristol BS2 8HW, UK
| | - Kirsty Phillips
- Department of Pathology, University Hospitals Bristol NHS Foundation Trust, Bristol BS2 8HW, UK
| | - Ben Gibbison
- Department of Anaesthesia, Bristol Medical School, University of Bristol, Bristol BS2 8HW, UK
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Grindstaff JL, Beaty LE, Ambardar M, Luttbeg B. Integrating theoretical and empirical approaches for a robust understanding of endocrine flexibility. J Exp Biol 2022; 225:274311. [PMID: 35258612 PMCID: PMC8987727 DOI: 10.1242/jeb.243408] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
There is growing interest in studying hormones beyond single 'snapshot' measurements, as recognition that individual variation in the endocrine response to environmental change may underlie many rapid, coordinated phenotypic changes. Repeated measures of hormone levels in individuals provide additional insight into individual variation in endocrine flexibility - that is, how individuals modulate hormone levels in response to the environment. The ability to quickly and appropriately modify phenotype is predicted to be favored by selection, especially in unpredictable environments. The need for repeated samples from individuals can make empirical studies of endocrine flexibility logistically challenging, but methods based in mathematical modeling can provide insights that circumvent these challenges. Our Review introduces and defines endocrine flexibility, reviews existing studies, makes suggestions for future empirical work, and recommends mathematical modeling approaches to complement empirical work and significantly advance our understanding. Mathematical modeling is not yet widely employed in endocrinology, but can be used to identify innovative areas for future research and generate novel predictions for empirical testing.
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Affiliation(s)
| | - Lynne E Beaty
- School of Science, Penn State Erie - The Behrend College, Erie, PA 16563, USA
| | - Medhavi Ambardar
- Department of Biological Sciences, Fort Hays State University, Hays, KS 67601, USA
| | - Barney Luttbeg
- Department of Integrative Biology, Oklahoma State University, OK 74078, USA
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21
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Gil NL, Azevedo GA, Balbino AM, Silva MM, Carvalho MHC, Akamine EH, Keller AC, Landgraf RG, Landgraf MA. Intrauterine growth restriction leads to a high-corticosterone producing offspring: An implication for pulmonary infection susceptibility. Life Sci 2021; 281:119764. [PMID: 34186045 DOI: 10.1016/j.lfs.2021.119764] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 06/15/2021] [Accepted: 06/22/2021] [Indexed: 11/28/2022]
Abstract
AIMS Although intrauterine growth restriction (IUGR) impairs immune system homeostasis and lung development, its relationship with the susceptibility to pulmonary infections remains unclear. Thus, this study aimed to investigate the impact of IUGR on acute lung inflammatory response induced by bacterial stimulus. MATERIALS AND METHODS Pregnant female Wistar rats were subjected to 50% caloric-protein food restriction during gestation. To mimic bacterial lung infection, adult male offspring (12 weeks old) were challenged with a single lipopolysaccharide (LPS) intranasal instillation, and 6 h later, we assessed the acute inflammatory response. Normal birth weight (NBW) animals represent the control group. KEY FINDINGS LPS instillation increased the protein levels in the airways of both the NBW and low birth weight (LBW) groups, indicating vascular leakage. LBW animals exhibited a lower number of neutrophils, reduced production of interleukin-6 and macrophage-inflammatory protein-2 and decreased upregulation of intercellular adhesion molecule-1 gene expression in lung tissues. Further analysis revealed that the LBW group produced lower levels of prostaglandin-E2 and failed to secrete leukotriene-B4 upon LPS stimulation, which correlated with impaired cyclooxygenase-2 and 5-lipoxygenase expression. These results were probably associated with their inability to upregulate the expression of Toll-like receptor-4 and downstream signaling proteins, such as nuclear factor kappa-B, in the lungs. The LBW group also exhibited abnormal airway thickening and high corticosterone levels under basal conditions. SIGNIFICANCE This study suggests that IUGR-induced foetal programming in LBW offspring threatens HPA axis physiology and corticosterone biodisponibility, and impairs the innate response to bacterial antigens, increasing future susceptibility to pulmonary infection.
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Affiliation(s)
- Noemi L Gil
- Department of Pharmaceuticals Sciences, Universidade Federal de São Paulo-campus Diadema, Diadema, SP, Brazil
| | - Gabriela A Azevedo
- Department of Pharmaceuticals Sciences, Universidade Federal de São Paulo-campus Diadema, Diadema, SP, Brazil
| | - Aleksandro M Balbino
- Department of Pharmaceuticals Sciences, Universidade Federal de São Paulo-campus Diadema, Diadema, SP, Brazil
| | - Marina M Silva
- Department of Pharmaceuticals Sciences, Universidade Federal de São Paulo-campus Diadema, Diadema, SP, Brazil
| | | | - Eliana H Akamine
- Department of Pharmacology, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Alexandre C Keller
- Department of Microbiology, Immunology and Parasitology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Richardt G Landgraf
- Department of Pharmaceuticals Sciences, Universidade Federal de São Paulo-campus Diadema, Diadema, SP, Brazil.
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22
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Malek H, Ebadzadeh MM, Safabakhsh R, Razavi A. Mathematical analysis of the role of pituitary-adrenal interactions in ultradian rhythms of the HPA axis. Comput Biol Med 2021; 135:104580. [PMID: 34166879 DOI: 10.1016/j.compbiomed.2021.104580] [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: 12/31/2020] [Revised: 06/09/2021] [Accepted: 06/12/2021] [Indexed: 11/29/2022]
Abstract
The hypothalamic-pituitary-adrenal (HPA) axis is a biological system in the human body that plays an important role in controlling stress and regulating various physiological elements, including the immune system, emotions, and moods in tense situations. Over the past two decades, several ordinary or delay differential equations models of the HPA axis have been proposed. In the majority of studies presented so far, corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol are among the main variables employed to build the HPA axis models. In the present study, based on a previously introduced hypothesis which asserts that ultradian rhythms in the HPA axis are produced by the pituitary-adrenal network alone and these rhythms can endure in the absence of CRH secretion, a simple two-dimensional delayed dynamical model of the HPA axis based on only ACTH and cortisol is introduced. The model is shown to be able to capture the ultradian (low frequency) rhythms of ACTH and cortisol released into the bloodstream. By mathematical analysis of the model using the Hopf bifurcation theorem, it is also demonstrated how oscillating solutions can emerge. Also, the model employs physiologically reasonable parameter values to exhibit how in the absence of CRH secretion, a simple model of the pituitary-adrenal interaction can be used to produce ultradian rhythms of both cortisol and ACTH hormones.
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Affiliation(s)
- Hamed Malek
- Faculty of Computer Science and Engineering, Shahid Beheshti University, Tehran, Iran.
| | | | - Reza Safabakhsh
- Computer and Information Technology Engineering Department, Amirkabir University of Technology, Tehran, Iran
| | - Alireza Razavi
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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23
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Amato S, Arnold A. Modeling Microglia Activation and Inflammation-Based Neuroprotectant Strategies During Ischemic Stroke. Bull Math Biol 2021; 83:72. [PMID: 33982158 DOI: 10.1007/s11538-021-00905-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 04/26/2021] [Indexed: 11/28/2022]
Abstract
Neural inflammation immediately follows the onset of ischemic stroke. During this process, microglial cells can be activated into two different phenotypes: the M1 phenotype, which can worsen brain injury by producing pro-inflammatory cytokines; or the M2 phenotype, which can aid in long term recovery by producing anti-inflammatory cytokines. In this study, we formulate a nonlinear system of differential equations to model the activation of microglia post-ischemic stroke, which includes bidirectional switching between the microglia phenotypes, as well as the interactions between these cells and the cytokines that they produce. Further, we explore neuroprotectant-based modeling strategies to suppress the activation of the detrimental M1 phenotype, while promoting activation of the beneficial M2 phenotype. Through use of global sensitivity techniques, we analyze the effects of the model parameters on the ratio of M1 to M2 microglia and the total number of activated microglial cells in the system over time. Results demonstrate the significance of bidirectional microglia phenotype switching on the ratio of M1 to M2 microglia, in both the absence and presence of neuroprotectant terms. Simulations further suggest that early inhibition of M1 activation and support of M2 activation leads to a decreased minimum ratio of M1 to M2 microglia and allows for a larger number of M2 than M1 cells for a longer time period.
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Affiliation(s)
- Sara Amato
- Department of Mathematical Sciences, Worcester Polytechnic Institute, Worcester, MA, USA
| | - Andrea Arnold
- Department of Mathematical Sciences, Worcester Polytechnic Institute, Worcester, MA, USA.
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24
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Baranova J, Dragunas G, Botellho MCS, Ayub ALP, Bueno-Alves R, Alencar RR, Papaiz DD, Sogayar MC, Ulrich H, Correa RG. Autism Spectrum Disorder: Signaling Pathways and Prospective Therapeutic Targets. Cell Mol Neurobiol 2021; 41:619-649. [PMID: 32468442 PMCID: PMC11448616 DOI: 10.1007/s10571-020-00882-7] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 05/16/2020] [Indexed: 12/11/2022]
Abstract
The Autism Spectrum Disorder (ASD) consists of a prevalent and heterogeneous group of neurodevelopmental diseases representing a severe burden to affected individuals and their caretakers. Despite substantial improvement towards understanding of ASD etiology and pathogenesis, as well as increased social awareness and more intensive research, no effective drugs have been successfully developed to resolve the main and most cumbersome ASD symptoms. Hence, finding better treatments, which may act as "disease-modifying" agents, and novel biomarkers for earlier ASD diagnosis and disease stage determination are needed. Diverse mutations of core components and consequent malfunctions of several cell signaling pathways have already been found in ASD by a series of experimental platforms, including genetic associations analyses and studies utilizing pre-clinical animal models and patient samples. These signaling cascades govern a broad range of neurological features such as neuronal development, neurotransmission, metabolism, and homeostasis, as well as immune regulation and inflammation. Here, we review the current knowledge on signaling pathways which are commonly disrupted in ASD and autism-related conditions. As such, we further propose ways to translate these findings into the development of genetic and biochemical clinical tests for early autism detection. Moreover, we highlight some putative druggable targets along these pathways, which, upon further research efforts, may evolve into novel therapeutic interventions for certain ASD conditions. Lastly, we also refer to the crosstalk among these major signaling cascades as well as their putative implications in therapeutics. Based on this collective information, we believe that a timely and accurate modulation of these prominent pathways may shape the neurodevelopment and neuro-immune regulation of homeostatic patterns and, hopefully, rescue some (if not all) ASD phenotypes.
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Affiliation(s)
- Juliana Baranova
- Department of Biochemistry, Chemistry Institute, University of São Paulo, Avenida Professor Lineu Prestes 748, Butantã, São Paulo, SP, 05508-000, Brazil
| | - Guilherme Dragunas
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Avenida Professor Lineu Prestes 1524, Butantã, São Paulo, SP, 05508-000, Brazil
| | - Mayara C S Botellho
- Department of Biochemistry, Chemistry Institute, University of São Paulo, Avenida Professor Lineu Prestes 748, Butantã, São Paulo, SP, 05508-000, Brazil
| | - Ana Luisa P Ayub
- Department of Pharmacology, Federal University of São Paulo, Rua Pedro de Toledo 669, Vila Clementino, São Paulo, SP, 04039-032, Brazil
| | - Rebeca Bueno-Alves
- Department of Biochemistry, Chemistry Institute, University of São Paulo, Avenida Professor Lineu Prestes 748, Butantã, São Paulo, SP, 05508-000, Brazil
| | - Rebeca R Alencar
- Department of Biochemistry, Chemistry Institute, University of São Paulo, Avenida Professor Lineu Prestes 748, Butantã, São Paulo, SP, 05508-000, Brazil
| | - Debora D Papaiz
- Department of Pharmacology, Federal University of São Paulo, Rua Pedro de Toledo 669, Vila Clementino, São Paulo, SP, 04039-032, Brazil
| | - Mari C Sogayar
- Department of Biochemistry, Chemistry Institute, University of São Paulo, Avenida Professor Lineu Prestes 748, Butantã, São Paulo, SP, 05508-000, Brazil
- Cell and Molecular Therapy Center, School of Medicine, University of São Paulo, Rua Pangaré 100 (Edifício NUCEL), Butantã, São Paulo, SP, 05360-130, Brazil
| | - Henning Ulrich
- Department of Biochemistry, Chemistry Institute, University of São Paulo, Avenida Professor Lineu Prestes 748, Butantã, São Paulo, SP, 05508-000, Brazil
| | - Ricardo G Correa
- NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA.
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25
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Nobile B, Durand M, Olié E, Guillaume S, Molès JP, Haffen E, Courtet P. The Anti-inflammatory Effect of the Tricyclic Antidepressant Clomipramine and Its High Penetration in the Brain Might Be Useful to Prevent the Psychiatric Consequences of SARS-CoV-2 Infection. Front Pharmacol 2021; 12:615695. [PMID: 33767623 PMCID: PMC7985338 DOI: 10.3389/fphar.2021.615695] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 02/04/2021] [Indexed: 12/12/2022] Open
Abstract
At the time of writing (December 2020), coronavirus disease 2019 (COVID-19) has already caused more than one million deaths worldwide, and therefore, it is imperative to find effective treatments. The “cytokine storm” induced by Severe Acute Respiratory Syndrome-Coronavirus type 2 (SARS-CoV-2) is a good target to prevent disease worsening, as indicated by the results obtained with tocilizumab and dexamethasone. SARS-CoV-2 can also invade the brain and cause neuro-inflammation with dramatic neurological manifestations, such as viral encephalitis. This could lead to potentially incapacitating long-term consequences, such as the development of psychiatric disorders, as previously observed with SARS-CoV. Several pathways/mechanisms could explain the link between viral infection and development of psychiatric diseases, especially neuro-inflammation induced by SARS-CoV-2. Therefore, it is important to find molecules with anti-inflammatory properties that penetrate easily into the brain. For instance, some antidepressants have anti-inflammatory action and pass easily through the blood brain barrier. Among them, clomipramine has shown very strong anti-inflammatory properties in vitro, in vivo (animal models) and human studies, especially in the brain. The aim of this review is to discuss the potential application of clomipramine to prevent post-infectious mental complications. Repositioning and testing antidepressants for COVID-19 management could help to reduce peripheral and especially central inflammation and to prevent the acute and particularly the long-term consequences of SARS-CoV-2 infection.
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Affiliation(s)
- B Nobile
- Department of Emergency Psychiatry and Acute Care, CHU Montpellier, Montpellier, France.,IGF, Univ. Montpellier, CNRS, INSERM, Montpellier, France
| | - M Durand
- Pathogenesis and Control of Chronic Infection, University of Montpellier, INSERM, EFS; CHU Montpellier, Montpellier, France
| | - E Olié
- Department of Emergency Psychiatry and Acute Care, CHU Montpellier, Montpellier, France.,IGF, Univ. Montpellier, CNRS, INSERM, Montpellier, France.,FondaMental Foundation, Créteil, France
| | - S Guillaume
- Department of Emergency Psychiatry and Acute Care, CHU Montpellier, Montpellier, France.,IGF, Univ. Montpellier, CNRS, INSERM, Montpellier, France.,FondaMental Foundation, Créteil, France
| | - J P Molès
- Pathogenesis and Control of Chronic Infection, University of Montpellier, INSERM, EFS; CHU Montpellier, Montpellier, France
| | - E Haffen
- FondaMental Foundation, Créteil, France.,Service de Psychiatrie de l'Adulte, CIC-1431 INSERM, CHU de Besançon, Laboratoire de Neurosciences, Université de Franche-Comté, Besancon, France
| | - P Courtet
- Department of Emergency Psychiatry and Acute Care, CHU Montpellier, Montpellier, France.,IGF, Univ. Montpellier, CNRS, INSERM, Montpellier, France.,FondaMental Foundation, Créteil, France
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26
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Arbel R, Segel-Karpas D, Chopik W. Optimism, pessimism, and health biomarkers in older couples. Br J Health Psychol 2020; 25:1055-1073. [PMID: 32914524 DOI: 10.1111/bjhp.12466] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 07/21/2020] [Accepted: 07/27/2020] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Studies have demonstrated the importance of optimism in predicting perceived general health. However, the handful of studies focusing on cardiovascular biomarkers show inconsistent effects. Additionally, no study examined whether spousal levels of optimism and pessimism affect an individual's biological markers of cardiovascular health. Thus, our objectives were to examine whether partners' optimism and pessimism affect individual biological markers, differentiating between between-dyad associations and within-dyad predictive processes. METHODS Three waves of the Health and Retirement Study collected in 2006, 2010, and 2014 were used to test actor and partner effects of optimism and pessimism on C-reactive protein (CRP) and high-density lipoprotein. Multilevel longitudinal actor-partner models were used to examine the contribution of a partner's optimism and pessimism to each biomarker, adjusting for respondent's age, sex, depression, body mass index, daily activity levels, and a summary score of respondent's doctor-diagnosed chronic conditions. RESULTS Partners' pessimism and optimism levels were moderately associated. Results for within-person effects were all non-significant, both within and across waves. Associations at the between-person level were also non-significant, with the exception of a positive association between husbands' pessimism and their own CRP, and husbands' optimism and their wives' CRP. CONCLUSIONS Results suggest that optimism and pessimism may not play a pertinent role in within variability of biomarkers of cardiovascular diseases and have a minor role in predicting to between-person variability of biomarkers of cardiovascular diseases.
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Affiliation(s)
- Reout Arbel
- Department of Counseling and Human Development, The Faculty of Education, University of Haifa, Israel
| | | | - William Chopik
- Department of Psychology, Michigan State University, East Lansing, Michigan, USA
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27
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Tallon J, Browning B, Couenne F, Bordes C, Venet F, Nony P, Gueyffier F, Moucadel V, Monneret G, Tayakout-Fayolle M. Dynamical modeling of pro- and anti-inflammatory cytokines in the early stage of septic shock. In Silico Biol 2020; 14:101-121. [PMID: 32597796 PMCID: PMC7505012 DOI: 10.3233/isb-200474] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
A dynamical model of the pathophysiological behaviors of IL18 and IL10 cytokines with their receptors is tested against data for the case of early sepsis. The proposed approach considers the surroundings (organs and bone marrow) and the different subsystems (cells and cyctokines). The interactions between blood cells, cytokines and the surroundings are described via mass balances. Cytokines are adsorbed onto associated receptors at the cell surface. The adsorption is described by the Langmuir model and gives rise to the production of more cytokines and associated receptors inside the cell. The quantities of pro and anti-inflammatory cytokines present in the body are combined to give global information via an inflammation level function which describes the patient’s state. Data for parameter estimation comes from the Sepsis 48 H database. Comparisons between patient data and simulations are presented and are in good agreement. For the IL18/IL10 cytokine pair, 5 key parameters have been found. They are linked to pro-inflammatory IL18 cytokine and show that the early sepsis is driven by components of inflammatory character.
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Affiliation(s)
- J Tallon
- Université Claude Bernard Lyon 1, CNRS, LAGEPP UMR 5007, Villeurbanne, France
| | - B Browning
- Université Claude Bernard Lyon 1, CNRS, LAGEPP UMR 5007, Villeurbanne, France
| | - F Couenne
- Université Claude Bernard Lyon 1, CNRS, LAGEPP UMR 5007, Villeurbanne, France
| | - C Bordes
- Université Claude Bernard Lyon 1, CNRS, LAGEPP UMR 5007, Villeurbanne, France
| | - F Venet
- Hospices Civils de Lyon, LYON Cedex 03 - France
| | - P Nony
- Université Claude Bernard Lyon 1, CNRS, LBBE UMR 5558, Lyon, France
| | - F Gueyffier
- Université Claude Bernard Lyon 1, CNRS, LBBE UMR 5558, Lyon, France
| | | | - G Monneret
- Hospices Civils de Lyon, LYON Cedex 03 - France
| | - M Tayakout-Fayolle
- Université Claude Bernard Lyon 1, CNRS, LAGEPP UMR 5007, Villeurbanne, France
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28
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Chaves RDC, Mallmann ASV, de Oliveira NF, Capibaribe VCC, da Silva DMA, Lopes IS, Valentim JT, Barbosa GR, de Carvalho AMR, Fonteles MMDF, Gutierrez SJC, Barbosa Filho JM, de Sousa FCF. The neuroprotective effect of Riparin IV on oxidative stress and neuroinflammation related to chronic stress-induced cognitive impairment. Horm Behav 2020; 122:104758. [PMID: 32304685 DOI: 10.1016/j.yhbeh.2020.104758] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Revised: 04/08/2020] [Accepted: 04/10/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND Cognitive impairment is identified as one of the diagnostic criteria for major depressive disorder and can extensively affect the quality of life of patients. Based on these findings, this study aimed to investigate the possible effects of Riparin IV (Rip IV) on cognitive impairment induced by chronic administration of corticosterone in mice. METHODS Female Swiss mice were divided into four groups: control (Control), corticosterone (Cort), Riparin IV (Cort + Rip IV), and Fluvoxamine (Cort + Flu). Three groups were administered corticosterone (20 mg/kg) subcutaneously during the 22-day study, while the control group received only vehicle. After the 14th day, the groups were administered medications: Riparin IV (Rip IV), fluvoxamine (Flu), or distilled water, by gavage, 1 h after the subcutaneous injections. After treatment, mice underwent behavioral testing, and brain areas were removed for oxidative stress and cytokine content assays. RESULTS The results revealed that Cort-treated mice developed a cognitive impairment and exhibited a neuroinflammatory profile with an oxidative load and Th1/Th2 cytokine imbalance. Rip IV treatment significantly ameliorated the cognitive deficit induced by Cort and displayed a neuroprotective effect. CONCLUSION The antidepressant-like ability of Rip IV treatment against chronic Cort-induced stress may be due to its potential to mitigate inflammatory damage and oxidative stress. The antioxidant and anti-inflammatory effect observed indicates Rip IV as a possible drug for antidepressant treatment of non-responsive patients with severe and cognitive symptoms.
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Affiliation(s)
- Raquell de Castro Chaves
- Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Auriana Serra Vasconcelos Mallmann
- Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Natália Ferreira de Oliveira
- Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Victor Celso Cavalcanti Capibaribe
- Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Daniel Moreira Alves da Silva
- Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Iardja Stéfane Lopes
- Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - José Tiago Valentim
- Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Giovanna Riello Barbosa
- Multi-User Facility, Drug Research and Development Center, Federal University of Ceará, Brazil
| | - Alyne Mara Rodrigues de Carvalho
- Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | | | - Stanley Juan Chavez Gutierrez
- Laboratory of Pharmaceutical Chemistry, Department of Biochemistry and Pharmacology, Federal University of Piauí, Teresina, Piauí, Brazil
| | - José Maria Barbosa Filho
- Laboratory of Pharmaceutical Technology, Department of Pharmaceutical Science, Federal University of Paraiba, João Pessoa, Paraiba, Brazil
| | - Francisca Cléa Florenço de Sousa
- Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
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29
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Oh J, Kim DH, Kim GY, Park EJ, Ryu JH, Jung JW, Park SJ, Kim GW, Lee S. Hydrangeae Dulcis Folium Attenuates Physical Stress by Supressing ACTH-Induced Cortisol in Zebrafish. Chin J Integr Med 2019; 26:130-137. [DOI: 10.1007/s11655-019-3204-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/31/2018] [Indexed: 12/11/2022]
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30
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Desgeorges T, Caratti G, Mounier R, Tuckermann J, Chazaud B. Glucocorticoids Shape Macrophage Phenotype for Tissue Repair. Front Immunol 2019; 10:1591. [PMID: 31354730 PMCID: PMC6632423 DOI: 10.3389/fimmu.2019.01591] [Citation(s) in RCA: 71] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Accepted: 06/25/2019] [Indexed: 12/16/2022] Open
Abstract
Inflammation is a complex process which is highly conserved among species. Inflammation occurs in response to injury, infection, and cancer, as an allostatic mechanism to return the tissue and to return the organism back to health and homeostasis. Excessive, or chronic inflammation is associated with numerous diseases, and thus strategies to combat run-away inflammation is required. Anti-inflammatory drugs were therefore developed to switch inflammation off. However, the inflammatory response may be beneficial for the organism, in particular in the case of sterile tissue injury. The inflammatory response can be divided into several parts. The first step is the mounting of the inflammatory reaction itself, characterized by the presence of pro-inflammatory cytokines, and the infiltration of immune cells into the injured area. The second step is the resolution phase, where immune cells move toward an anti-inflammatory phenotype and decrease the secretion of pro-inflammatory cytokines. The last stage of inflammation is the regeneration process, where the tissue is rebuilt. Innate immune cells are major actors in the inflammatory response, of which, macrophages play an important role. Macrophages are highly sensitive to a large number of environmental stimuli, and can adapt their phenotype and function on demand. This change in phenotype in response to the environment allow macrophages to be involved in all steps of inflammation, from the first mounting of the pro-inflammatory response to the post-damage tissue repair.
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Affiliation(s)
- Thibaut Desgeorges
- Institut NeuroMyoGène, Université Claude Bernard Lyon 1, Univ Lyon, CNRS UMR 5310, INSERM U1217, Lyon, France
| | - Giorgio Caratti
- Institute of Comparative Molecular Endocrinology, University of Ulm, Ulm, Germany
| | - Rémi Mounier
- Institut NeuroMyoGène, Université Claude Bernard Lyon 1, Univ Lyon, CNRS UMR 5310, INSERM U1217, Lyon, France
| | - Jan Tuckermann
- Institute of Comparative Molecular Endocrinology, University of Ulm, Ulm, Germany
| | - Bénédicte Chazaud
- Institut NeuroMyoGène, Université Claude Bernard Lyon 1, Univ Lyon, CNRS UMR 5310, INSERM U1217, Lyon, France
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31
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Tsyglakova M, McDaniel D, Hodes GE. Immune mechanisms of stress susceptibility and resilience: Lessons from animal models. Front Neuroendocrinol 2019; 54:100771. [PMID: 31325456 DOI: 10.1016/j.yfrne.2019.100771] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Revised: 06/17/2019] [Accepted: 07/09/2019] [Indexed: 12/12/2022]
Abstract
Stress has an impact on the brain and the body. A growing literature demonstrates that feedback between the peripheral immune system and the brain contributes to individual differences in the behavioral response to stress. Here we examine preclinical literature to demonstrate a holistic vision of risk and resilience to stress. We identify a variety of cellular, cytokine and molecular mechanisms in adult animals that act in concert to produce a stress susceptible individual response. We discuss how cross talk between immune cells in the brain and in the periphery act together to increase permeability across the blood brain barrier or block it, resulting in susceptible or stress resilient phenotype. These preclinical studies have importance for understanding how individual differences in the immune response to stress may be contributing to mood related disorders such as depression, anxiety and posttraumatic stress disorders.
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Affiliation(s)
- Mariya Tsyglakova
- School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA; Graduate Program in Translational Biology, Medicine and Health, Virginia Tech, Blacksburg, VA, USA
| | - Dylan McDaniel
- School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
| | - Georgia E Hodes
- School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
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32
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Nowakowski S, Matthews KA, von Känel R, Hall MH, Thurston RC. Sleep characteristics and inflammatory biomarkers among midlife women. Sleep 2019; 41:4956860. [PMID: 29617910 DOI: 10.1093/sleep/zsy049] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2017] [Accepted: 02/12/2018] [Indexed: 12/19/2022] Open
Abstract
Study Objectives Research suggests that sleep disturbances are associated with elevated levels of inflammation. Some evidence indicates that women may be particularly vulnerable; increased levels of inflammatory biomarkers with sleep disturbances are primarily observed among women. Midlife, which encompasses the menopause transition, is typically reported as a time of poor sleep. We tested whether poorer objectively measured sleep characteristics were related to a poorer inflammatory profile in midlife women. Methods Two hundred ninety-five peri- and postmenopausal women aged 40-60 completed 3 days of wrist actigraphy, physiologic hot flash monitoring, questionnaires (e.g. Berlin sleep apnea risk questionnaire], and a blood draw for the assessment of inflammatory markers, including C-reactive protein (CRP), interleukin-6 (IL-6), and von Willebrand factor (VWF) antigen. Associations of objective (actigraphy) sleep with inflammatory markers were tested in regression models. Sleep efficiency was inverse log transformed. Covariates included age, race/ethnicity, education, body mass index, sleep apnea risk, homeostatic model assessment (a measure of insulin resistance), systolic blood pressure, low-density lipoprotein cholesterol, and physical activity. Results In separate models controlling for age, race/ethnicity, and education, lower sleep efficiency was associated with higher IL-6 [b(SE) = .02 (.10), p = .003] and VWF [b(SE) = .02 (.08), p = .002]. More minutes awake after sleep onset was associated with higher VWF [b(SE) = .12 (.06), p = .01]. Findings persisted in multivariable models. Conclusions Lower sleep efficiency and more minutes awake after sleep onset were independently associated with higher circulating levels of VWF. Lower sleep efficiency was associated with higher circulating levels of IL-6. These findings suggest that sleep disturbances are associated with greater circulating inflammation in midlife women.
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Affiliation(s)
- Sara Nowakowski
- Department of Obstetrics & Gynecology, University of Texas Medical Branch, Galveston, TX.,Department of Psychiatry & Behavioral Sciences, University of Texas Medical Branch, Galveston, TX
| | - Karen A Matthews
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA.,Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA.,Department of Psychology, University of Pittsburgh, Pittsburgh, PA
| | - Roland von Känel
- Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Martica H Hall
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA.,Department of Psychology, University of Pittsburgh, Pittsburgh, PA
| | - Rebecca C Thurston
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA.,Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA.,Department of Psychology, University of Pittsburgh, Pittsburgh, PA
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33
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Yu H, Zhang F, Guan X. Baicalin reverse depressive-like behaviors through regulation SIRT1-NF-kB signaling pathway in olfactory bulbectomized rats. Phytother Res 2019; 33:1480-1489. [PMID: 30848526 DOI: 10.1002/ptr.6340] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2018] [Revised: 02/02/2019] [Accepted: 02/15/2019] [Indexed: 11/08/2022]
Abstract
Depression is a common and detrimental illness that affects up to 120 million people worldwide. The present study was designed to evaluate the antidepressant-like effects and mechanisms of baicalin on olfactory bulbectomized model of depression. Baicalin treatment (20 and 40 mg/kg) significantly reversed the abnormal levels of sucrose consumption, open field test, and forced swimming test. Treatments with baicalin reversed the olfactory bulbectomized-induced alterations of serum corticosterone levels to a great extent. Our results further demonstrated that baicalin administration negatively regulated the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF-α) in the hippocampus and hypothalamus. Furthermore, baicalin regulated Sirtuin 1 (SIRT1) and decreased the levels of p65 acetylation (ac-p65) in the hippocampus and hypothalamus. Moreover, in lipopolysaccharides-induced BV-2 cells, the levels of inflammatory factors (IL-1β), p65 acetylation at lysine 310, and SIRT1 expression were different in the group treated with both baicalin and nicotinamide compared with the group treated with baicalin, which suggests that baicalin regulates SIRT1 and thereby inhibits p65 acetylation. In summary, administration of baicalin reduces the levels of pro-inflammatory cytokines, possibly through regulation of SIRT1-NF-kB pathway. Our findings suggest a support into the potential of baicalin in therapeutic effect for depression.
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Affiliation(s)
- Haiyang Yu
- School of Pharmaceutical Sciences, Taishan Medical University, Taian, China.,Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, New York
| | - Fangfang Zhang
- School of Pharmaceutical Sciences, Taishan Medical University, Taian, China
| | - Xidong Guan
- School of Pharmaceutical Sciences, Taishan Medical University, Taian, China
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Immune system modelling in case of a septic shock. ACTA ACUST UNITED AC 2019. [DOI: 10.1016/b978-0-12-818634-3.50183-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register]
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Stanojević A, Marković VM, Čupić Ž, Kolar-Anić L, Vukojević V. Advances in mathematical modelling of the hypothalamic–pituitary–adrenal (HPA) axis dynamics and the neuroendocrine response to stress. Curr Opin Chem Eng 2018. [DOI: 10.1016/j.coche.2018.04.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Pro-inflammatory Cytokines and Oxidized Low-Density-Lipoprotein in Patients With Fibromyalgia. Arch Rheumatol 2018; 34:123-129. [PMID: 31497758 DOI: 10.5606/archrheumatol.2019.6733] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Accepted: 05/05/2018] [Indexed: 12/24/2022] Open
Abstract
Objectives This study aims to evaluate the differences in serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), (IL-8), and oxidized low-density lipoprotein (Ox-LDL) between female fibromyalgia (FM) patients and healthy females and also to examine a possible relationship between the cytokines/biomarker and the severity of pain and clinical features of FM. Patients and methods This case-control study included 48 female patients (mean age 26.51±6.98 years; range, 18 to 50 years) who were diagnosed with FM according to the American College of Rheumatology criteria and 43 healthy female subjects (mean age 23.93±4.22 years; range, 18 to 50 years). Serum levels of TNF-α, IL-1β, IL-8, and Ox-LDL were measured by enzyme-linked immunosorbent assay in both groups. Fibromyalgia Impact Questionnaire, Visual Analog Scale, symptom severity scale, and widespread pain index were carried out and also their relationships with TNF-α, IL-1β, IL-8, and Ox-LDL levels were evaluated. Results There was no difference in levels of the serum TNF-α, IL-1β, IL-8, and Ox-LDL between FM patients and healthy controls (p>0.05). The severity of pain was significantly associated with TNF-α (r=0.338; p=0.021) and IL-8 (r=0.299; p=0.043) levels, and Ox-LDL (r=0.415; p=0.006) level was found to be related to symptom severity of FM. Conclusion Our results suggest that serum levels of TNF-α and IL-8 may be involved in the occurrence of pain in FM. The level of Ox-LDL may play an important role in the severity of symptoms. Future studies are needed to determine whether and how Ox-LDL plays a role in FM.
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Abstract
Fibromyalgia appears to present in subgroups with regard to biological pain induction, with primarily inflammatory, neuropathic/neurodegenerative, sympathetic, oxidative, nitrosative, or muscular factors and/or central sensitization. Recent research has also discussed glial activation or interrupted dopaminergic neurotransmission, as well as increased skin mast cells and mitochondrial dysfunction. Therapy is difficult, and the treatment options used so far mostly just have the potential to address only one of these aspects. As ambroxol addresses all of them in a single substance and furthermore also reduces visceral hypersensitivity, in fibromyalgia existing as irritable bowel syndrome or chronic bladder pain, it should be systematically investigated for this purpose. Encouraged by first clinical observations of two working groups using topical or oral ambroxol for fibromyalgia treatments, the present paper outlines the scientific argument for this approach by looking at each of the aforementioned aspects of this complex disease and summarizes putative modes of action of ambroxol. Nevertheless, at this point the evidence basis for ambroxol is not strong enough for clinical recommendation.
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Affiliation(s)
- Kai-Uwe Kern
- Institute of Pain Medicine/Pain Practice, Wiesbaden, Germany
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Abstract
The hypothalamic-pituitary-adrenal axis is a dynamic system regulating glucocorticoid hormone synthesis in the adrenal glands. Many key factors within the adrenal steroidogenic pathway have been identified and studied, but little is known about how these factors function collectively as a dynamic network of interacting components. To investigate this, we developed a mathematical model of the adrenal steroidogenic regulatory network that accounts for key regulatory processes occurring at different timescales. We used our model to predict the time evolution of steroidogenesis in response to physiological adrenocorticotropic hormone (ACTH) perturbations, ranging from basal pulses to larger stress-like stimulations (e.g., inflammatory stress). Testing these predictions experimentally in the rat, our results show that the steroidogenic regulatory network architecture is sufficient to respond to both small and large ACTH perturbations, but coupling this regulatory network with the immune pathway is necessary to explain the dissociated dynamics between ACTH and glucocorticoids observed under conditions of inflammatory stress.
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Bergler-Czop B, Miziołek B, Brzezińska-Wcisło L. Alopecia areata - hyperactivity of the hypothalamic-pituitary-adrenal axis is a myth? J Eur Acad Dermatol Venereol 2017; 31:1555-1561. [DOI: 10.1111/jdv.14346] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Accepted: 04/19/2017] [Indexed: 12/30/2022]
Affiliation(s)
- B. Bergler-Czop
- Department of Dermatology; School of Medicine in Katowice; Medical University of Silesia in Katowice; Katowice Poland
| | - B. Miziołek
- Department of Dermatology; Andrzej Mielęcki Silesian Independent Public Clinic in Katowice; Katowice Poland
| | - L. Brzezińska-Wcisło
- Department of Dermatology; School of Medicine in Katowice; Medical University of Silesia in Katowice; Katowice Poland
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Aranda G, Lopez C, Fernandez-Ruiz R, Esteban Y, Garcia-Eguren G, Mora M, Halperin I, Casals G, Enseñat J, Hanzu FA. Circulatory Immune Cells in Cushing Syndrome: Bystanders or Active Contributors to Atherometabolic Injury? A Study of Adhesion and Activation of Cell Surface Markers. Int J Endocrinol 2017; 2017:2912763. [PMID: 29213284 PMCID: PMC5632466 DOI: 10.1155/2017/2912763] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Revised: 06/18/2017] [Accepted: 07/16/2017] [Indexed: 02/06/2023] Open
Abstract
Glucocorticoids (GC) induce cardiometabolic risk while atherosclerosis is a chronic inflammation involving immunity. GC are immune suppressors, and the adrenocorticotrophic hormone (ACTH) has immune modulator activities. Both may act in atherothrombotic inflammation involving immune cells (IMNC). Aim. To investigate adhesion and activation surface cell markers (CDs) of peripheral IMNC in endogenous Cushing syndrome (CS) and the immune modulator role of ACTH. Material and Methods. 16 ACTH-dependent CS (ACTH-D), 10 ACTH-independent (ACTH-ID) CS, and 16 healthy controls (C) were included. Leukocytes (Leuc), monocytes (MN), lymphocytes (Lym), and neutrophils (N) were analyzed by flow cytometry for atherosclerosis previously associated with CDs. Results. Leuc, N, and MN correlated with CS (p < 0.05), WC (p < 0.001), WHR (p = 0.003), BMI (p < 0.001), and hs-CRP (p < 0.001). CD14++CD16+ (p = 0.047); CD14+CD16++ (p = 0.053) MN; CD15+ (p = 0.027); CD15+CD16+ (p = 0.008) N; and NK-Lym (p = 0.019) were higher in CS. CD14+CD16++ MN were higher in ACTH-ID (8.9 ± 3.5%) versus ACTH-D CS (4.2 ± 1.9%) versus C (4.9 ± 2.3%). NK-Lym correlated with c-LDL (r = 0.433, p = 0.039) and CD15+ N with hs-CRP (r = 0.446, p = 0.037). In multivariate analysis, Leuc, N, and MN depended on BMI (p = 0.021), WC (p = 0.002), and WHR (p = 0.014), while CD15+ and CD15+CD16+ N on hypercortisolism and CS (p = 0.035). Conclusion. In CS, IMNC present changes in activation and adhesion CDs implicated in atherothrombotic inflammation. ACTH-IDCS presents a particular IMNC phenotype, possibly due to the absence of the immune modulator effect of ACTH.
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Affiliation(s)
- Gloria Aranda
- Group of Endocrine Disorders, IDIBAPS, Barcelona, Spain
- Department of Endocrinology and Nutrition, Hospital Clinic Universitari, Barcelona, Spain
| | | | - Rebeca Fernandez-Ruiz
- Centro de Investigación en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain
| | - Yaiza Esteban
- Centro de Investigación en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain
| | | | - Mireia Mora
- Group of Endocrine Disorders, IDIBAPS, Barcelona, Spain
- Department of Endocrinology and Nutrition, Hospital Clinic Universitari, Barcelona, Spain
- Centro de Investigación en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain
- University of Barcelona, Barcelona, Spain
| | - Irene Halperin
- Group of Endocrine Disorders, IDIBAPS, Barcelona, Spain
- Department of Endocrinology and Nutrition, Hospital Clinic Universitari, Barcelona, Spain
- Centro de Investigación en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain
- University of Barcelona, Barcelona, Spain
| | - Gregori Casals
- Biochemistry and Molecular Genetics Service, Hospital Clinic Universitari and IDIBAPS and CIBERehd, Barcelona, Spain
| | - Joaquim Enseñat
- University of Barcelona, Barcelona, Spain
- Department of Neurosurgery, Hospital Clinic Universitari, Barcelona, Spain
| | - Felicia A. Hanzu
- Group of Endocrine Disorders, IDIBAPS, Barcelona, Spain
- Department of Endocrinology and Nutrition, Hospital Clinic Universitari, Barcelona, Spain
- Centro de Investigación en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain
- University of Barcelona, Barcelona, Spain
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Regulation of hypothalamic-pituitary-adrenal axis activity and immunologic function contributed to the anti-inflammatory effect of acupuncture in the OVA-induced murine asthma model. Neurosci Lett 2016; 636:177-183. [PMID: 27816549 DOI: 10.1016/j.neulet.2016.11.001] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2016] [Revised: 10/17/2016] [Accepted: 11/01/2016] [Indexed: 02/07/2023]
Abstract
Asthma is a complex inflammatory disease of the airways and acupuncture is one of the effective therapies widely used to treat asthma in China. The aim of the study was to evaluate the regulatory role of acupuncture in airway inflammation and the hypothalamic-pituitary-adrenal (HPA) axis activity in OVA-induced murine asthma model. Our results demonstrated that acupuncture was effective in suppression of AHR, inhibition of total leukocyte, neutrophil, lymphocyte and eosinophil counts in BALF, attenuation of airway inflammation and TNF-α, IL-1β, IL-5 and eotaxin secretion. Furthermore, the HPA axis activity was also regulated by acupuncture, which included promotion of adrenocorticotropic hormone and cortisol secretion in the plasma. Our findings revealed that acupuncture could attenuate airway inflammation and regulate HPA axis and immunologic function in the OVA-induced murine asthma model, which may provide support to better understand the contribution of acupuncture to the regulation of airway inflammation and HPA axis activity in asthma.
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Mendieta D, la Cruz-Aguilera DLD, Barrera-Villalpando MI, Becerril-Villanueva E, Arreola R, Hernández-Ferreira E, Pérez-Tapia SM, Pérez-Sánchez G, Garcés-Alvarez ME, Aguirre-Cruz L, Velasco-Velázquez MA, Pavón L. IL-8 and IL-6 primarily mediate the inflammatory response in fibromyalgia patients. J Neuroimmunol 2016; 290:22-5. [PMID: 26711564 DOI: 10.1016/j.jneuroim.2015.11.011] [Citation(s) in RCA: 86] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Revised: 11/11/2015] [Accepted: 11/15/2015] [Indexed: 01/14/2023]
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