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Pérez AR, Bottasso OA, Santucci NE. Immune-endocrine crossroads: the impact of nuclear receptors in Tuberculosis and Chagas disease. Front Endocrinol (Lausanne) 2025; 16:1538376. [PMID: 39991733 PMCID: PMC11842248 DOI: 10.3389/fendo.2025.1538376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Accepted: 01/13/2025] [Indexed: 02/25/2025] Open
Abstract
Nuclear Receptors (NRs) comprise a superfamily of proteins with essential roles in cell signaling, survival, proliferation, and metabolism. They act as transcription factors and are subclassified into families based on their ligands, DNA-binding sequences, tissue specificity, and functions. Evidence indicates that in infectious diseases, cancer, and autoimmunity, NRs modulate immune and endocrine responses, altering the transcriptional profile of cells and organs and influencing disease progression. Chronic infectious diseases, characterized by pathogen persistence, are particularly notable for an exaggerated inflammatory process. Unlike acute inflammation, which helps the host respond to pathogens, chronic inflammation leads to metabolic disorders and a dysregulated neuro-immuno-endocrine response. Over time, disturbances in cytokine, hormone, and other compound production foster an unbalanced, detrimental defensive response. This complexity underscores the significant role of ligand-dependent NRs. Tuberculosis and Chagas Disease are two critical chronic infections. The causative agents, Mycobacterium tuberculosis and Trypanosoma cruzi, have developed evasion strategies to establish chronic infections. Their clinical manifestations are associated with disrupted immuno-endocrine responses, pointing to a potential involvement of NRs. This review explores the current understanding of NRs in regulating immune-endocrine interactions within the context Tuberculosis and Chagas Disease. These diseases remain significant global health concerns, particularly in developing countries, highlighting the importance of understanding the molecular mechanisms underlying host-pathogen interactions mediated by NRs.
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Affiliation(s)
- Ana R. Pérez
- Laboratorio de Estudios en Enfermedad de Chagas, Instituto de Inmunología Clínica y Experimental de Rosario (IDICER)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-Universidad Nacional de Rosario (UNR), Rosario, Argentina
- Facultad de Ciencias Médicas, Universidad Nacional de Rosario (UNR), Rosario, Argentina
| | - Oscar A. Bottasso
- Laboratorio de Estudios en Enfermedad de Chagas, Instituto de Inmunología Clínica y Experimental de Rosario (IDICER)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-Universidad Nacional de Rosario (UNR), Rosario, Argentina
- Facultad de Ciencias Médicas, Universidad Nacional de Rosario (UNR), Rosario, Argentina
- Laboratorio de Estudios en Tuberculosis, Instituto de Inmunología Clínica y Experimental de Rosario (IDICER)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-Universidad Nacional de Rosario (UNR), Rosario, Argentina
| | - Natalia E. Santucci
- Facultad de Ciencias Médicas, Universidad Nacional de Rosario (UNR), Rosario, Argentina
- Laboratorio de Estudios en Tuberculosis, Instituto de Inmunología Clínica y Experimental de Rosario (IDICER)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-Universidad Nacional de Rosario (UNR), Rosario, Argentina
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Zhao D, Sui Y, Sun Y. Causal Relationship Between Immune Cells and Hypopituitarism: Bidirectional Mendelian Randomization Study. World Neurosurg 2025; 194:123411. [PMID: 39522807 DOI: 10.1016/j.wneu.2024.10.140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Accepted: 10/31/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Hypopituitarism, one or more pituitary hormones inefficiently produced by the anterior pituitary or released from the posterior pituitary to adapt to the needs of the organism. Existing epidemiological data show that immune-mediated diffuse infiltration of the anterior pituitary is important in the development of hypopituitarism. However, the precise connection between immune cells and hypopituitarism remains unclear. This study aimed to elucidate the potential causal links between the 731 immune cell types and hypopituitarism risk. METHODS Based on data from a genome-wide association study, a bidirectional two-sample Mendelian randomization analysis was performed using 5 methods to explore the potential influence of immune cell phenotypes on hypopituitarism. Sensitivity analyses were conducted to examine the robustness of these findings. RESULTS Our findings support that B cells, T cells, Tregs, dendritic cells, monocytes, and myeloid cells each have a bidirectional influence on hypopituitarism. One B-cell phenotype was associated with increased hypopituitarism risk, while 2 B-cell phenotypes play a protective role in hypopituitarism. Moreover, 7 T-cell phenotypes demonstrate significant protective properties on hypopituitarism. Seven Tregs were associated with increased hypopituitarism risk. Furthermore, one monocyte was identified to be significantly associated with hypopituitarism risk. In addition, reverse Mendelian randomization analysis revealed that hypopituitarism was positively associated with 30 additional immune cell phenotypes and negatively associated with 17 immune cells. CONCLUSIONS Our investigation shed light on the intricate potential relationship between immune cells and hypopituitarism via genetic methods, underscoring the immune-mediated pathway in hypopituitarism pathogenesis, thereby offering valuable insights for future clinical investigations.
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Affiliation(s)
- Dadi Zhao
- Department of Neurosurgery, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Yuan Sui
- Department of Neurosurgery, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Yesheng Sun
- Department of Cellular Neurobiology, Zoological Institute, Technische Universität Braunschweig, Braunschweig, Germany.
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Ochoa-Amaya JE, Paula LDOA, Luciano FF, Bernardi MM. Repeated saline injections reduce the pulmonary allergic inflammatory response in rats by inducing short-term stress. Brain Behav Immun Health 2024; 40:100822. [PMID: 39144834 PMCID: PMC11320420 DOI: 10.1016/j.bbih.2024.100822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 06/28/2024] [Accepted: 07/15/2024] [Indexed: 08/16/2024] Open
Abstract
Purpose Asthma is characterized by pulmonary cell infiltration and hyper-responsiveness of the airways. Short-term stress reduces airway inflammation. Thus, in the present study, we examined the effects of short-term stress induced by repeated treatment with saline injections on the pulmonary allergic inflammatory response in rats. Methods Adult male rats were divided into three groups: Naïve group (non-sensitized, challenged, or treated rats), Control group (rats sensitized with ovalbumin (OVA) to induce lung inflammation), and Saline group (rats treated for five days with saline before OVA sensitization). Inhalation challenges were performed one week after the booster with aerosolized OVA. On day 18, the effect of saline injections on total and differential leukocytes in bronchoalveolar lavage (BAL), femoral marrow lavage (FML), and blood was evaluated. The percentage of mucus, serum corticosterone, collagen, cytokines in lung explants, and norepinephrine levels were also measured. Results OVA sensitization increased the circulating leukocytes and their migration to the lung, decreasing the bone marrow leukocytes. The repeated saline injections prevented this migration by decreasing the number of leukocytes in BAL and blood in the control group. Cytokine Interleukin-4 (IL-4) was higher in the control group than in the naive and saline groups; cytokines Interleukin-6 (IL-6), Interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNFα) were higher in the control and saline groups than in the naïve group; Interferon gamma (IFNγ) was higher in the saline group than in the naive and control groups; norepinephrine increased in animals sensitized with OVA and was higher only in the saline group relative to the naïve group. Conclusions These results suggest that short-term stress could contribute to the anti-allergic airway inflammation effects of a given treatment.
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Affiliation(s)
- Julieta Esperanza Ochoa-Amaya
- University of the Llanos, Faculty of Agricultural Sciences and Natural Resources, School of Animal Sciences, Colombia
- Department of Pathology, School of Veterinary Medicine, University of São Paulo, São Paulo, Brazil
| | - Ligeiro de Oliveira Ana Paula
- Post-Graduate Program in Biophotonics Applied to Health Sciences, University Nove de Julho (UNINOVE), São Paulo, Brazil
| | - Freitas Felicio Luciano
- Department of Pathology, School of Veterinary Medicine, University of São Paulo, São Paulo, Brazil
| | - Maria Martha Bernardi
- Psychoneuroimmunology Laboratory, Program in Environmental and Experimental Pathology, Paulista University, Rua Dr. Bacelar 1212, 04026-002, São Paulo, SP, Brazil
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Pamminger T, Basley K, Goulson D, Hughes WOH. Potential acetylcholine-based communication in honeybee haemocytes and its modulation by a neonicotinoid insecticide. PeerJ 2024; 12:e17978. [PMID: 39285925 PMCID: PMC11404474 DOI: 10.7717/peerj.17978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2018] [Accepted: 08/06/2024] [Indexed: 09/19/2024] Open
Abstract
There is growing concern that some managed and wild insect pollinator populations are in decline, potentially threatening biodiversity and sustainable food production on a global scale. In recent years, there has been increasing evidence that sub-lethal exposure to neurotoxic, neonicotinoid pesticides can negatively affect pollinator immunocompetence and could amplify the effects of diseases, likely contributing to pollinator declines. However, a direct pathway connecting neonicotinoids and immune functions remains elusive. In this study we show that haemocytes and non-neural tissues of the honeybee Apis mellifera express the building blocks of the nicotinic acetylcholine receptors that are the target of neonicotinoids. In addition, we demonstrate that the haemocytes, which form the cellular arm of the innate immune system, actively express choline acetyltransferase, a key enzyme necessary to synthesize acetylcholine. In a last step, we show that the expression of this key enzyme is affected by field-realistic doses of clothianidin, a widely used neonicotinoid. These results support a potential mechanistic framework to explain the effects of sub-lethal doses of neonicotinoids on the immune function of pollinators.
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Affiliation(s)
- Tobias Pamminger
- School of Life Sciences, University of Sussex, Brighton, UK
- Bayer AG, Monheim am Rhein, Germany
| | - Kate Basley
- School of Life Sciences, University of Sussex, Brighton, UK
| | - Dave Goulson
- School of Life Sciences, University of Sussex, Brighton, UK
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Smith C. The potential of zebrafish as drug discovery research tool in immune-mediated inflammatory disease. Inflammopharmacology 2024; 32:2219-2233. [PMID: 38926297 PMCID: PMC11300644 DOI: 10.1007/s10787-024-01511-1] [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: 02/01/2024] [Accepted: 06/06/2024] [Indexed: 06/28/2024]
Abstract
Immune-mediated inflammatory disease (IMID) prevalence is estimated at 3-7% for Westernised populations, with annual incidence reported at almost 1 in 100 people globally. More recently, drug discovery approaches have been evolving towards more targeted therapies with an improved long-term safety profile, while the requirement for individualisation of medicine in complex conditions such as IMIDs, is acknowledged. However, existing preclinical models-such as cellular and in vivo mammalian models-are not ideal for modern drug discovery model requirements, such as real-time in vivo visualisation of drug effects, logistically feasible safety assessment over the course of a lifetime, or dynamic assessment of physiological changes during disease development. Zebrafish share high homology with humans in terms of proteins and disease-causing genes, with high conservation of physiological processes at organ, tissue, cellular and molecular level. These and other unique attributes, such as high fecundity, relative transparency and ease of genetic manipulation, positions zebrafish as the next major role player in IMID drug discovery. This review provides a brief overview of the suitability of this organism as model for human inflammatory disease and summarises the range of approaches used in zebrafish-based drug discovery research. Strengths and limitations of zebrafish as model organism, as well as important considerations in research study design, are discussed. Finally, under-utilised avenues for investigation in the IMID context are highlighted.
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Affiliation(s)
- Carine Smith
- Experimental Medicine Group, Department of Medicine, Stellenbosch University, Parow, South Africa.
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Merritt JR, Ozga M, De Chavez PJD, Boolani A, Baker LB. No effect of tattoos on local sweat concentrations of select cytokines, cortisol, glucose, blood urea nitrogen, or lactate during exercise. Sci Rep 2024; 14:12570. [PMID: 38821996 PMCID: PMC11143332 DOI: 10.1038/s41598-024-63057-0] [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: 01/31/2024] [Accepted: 05/24/2024] [Indexed: 06/02/2024] Open
Abstract
Due to growing interest in the investigation of exercise induced sweat biomarkers to assess an individual's health and the increasing prevalence of tattoos in the world's population, investigators sought to determine whether local sweat concentrations and excretion rates of epidermal growth factor (EGF), interleukin (IL) -1α, IL-6, IL-8, cortisol, glucose, blood urea nitrogen (BUN), and lactate differ between tattooed and contralateral non-tattooed skin during exercise. Sixteen recreational exercisers [female (50%)] (age = 25-48 years) with ≥ 1 unilateral permanent tattoo [median tattoo age = 6 years, IQR = 5] on the arm/torso completed an outdoor group fitness session. There were no significant differences between tattooed and non-tattooed skin for sweat EGF, IL-1α, IL-8, cortisol, glucose, BUN, or lactate concentrations. There were no significant differences between tattooed and non-tattooed skin for sweat EGF, IL-1α, IL-8, cortisol, glucose, BUN, or lactate excretion rate. Findings suggest that permanent tattoos older than 1 year may not impact local sweat EGF, IL-1α, IL-8, cortisol, glucose, BUN, and lactate concentrations or excretion rates during exercise.Clinical trial identifier NCT04920266 was registered on June 9, 2021.
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Affiliation(s)
- James R Merritt
- Gatorade Sports Science Institute, PepsiCo R&D, Valhalla, NY, USA.
| | - Michal Ozga
- Gatorade Sports Science Institute, PepsiCo R&D, Valhalla, NY, USA
| | | | - Ali Boolani
- Gatorade Sports Science Institute, PepsiCo R&D, Valhalla, NY, USA
| | - Lindsay B Baker
- Gatorade Sports Science Institute, PepsiCo R&D, Valhalla, NY, USA
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King MA, Brown SD, Barnes KA, De Chavez PJD, Baker LB. Regional and time course differences in sweat cortisol, glucose, and select cytokine concentrations during exercise. Eur J Appl Physiol 2023; 123:1727-1738. [PMID: 37005963 PMCID: PMC10363073 DOI: 10.1007/s00421-023-05187-3] [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: 01/27/2023] [Accepted: 03/20/2023] [Indexed: 04/04/2023]
Abstract
INTRODUCTION The use of sweat as a biofluid for non-invasive sampling and diagnostics is a popular area of research. However, concentrations of cortisol, glucose, and cytokines have not been described across anatomical regions or as time progresses throughout exercise. PURPOSE To determine regional and time course differences in sweat cortisol, glucose, and select cytokines (EGF, IFN-γ, IL-1β, IL-1α, IL-1ra, TNF-α, IL-6, IL-8, and IL-10). METHODS Sweat was collected with absorbent patches from eight subjects (24-44 y; 80.2 ± 10.2 kg) on the forehead (FH), right dorsal forearm (RDF), right scapula (RS), and right triceps (RT) at 0-25 min, 30-55 min, and 60-85 min during 90 min of cycling (~ 82% HRmax) in a heated chamber (32 °C, 50% rh). ANOVA was used to determine the effect of site and time on outcomes. Data are reported as LS means ± SE. RESULTS There was a significant effect of location on sweat analyte concentrations with FH having higher values than most other regions for cortisol (FH: 1.15 ± 0.08 ng/mL > RDF: 0.62 ± 0.09 ng/mL and RT: 0.65 ± 0.12 ng/mL, P = 0.02), IL-1ra (P < 0.0001), and IL-8 (P < 0.0001), but lower concentrations for glucose (P = 0.01), IL-1α (P < 0.0001), and IL-10 (P = 0.02). Sweat IL-1β concentration was higher on the RS than RT (P < 0.0001). Sweat cortisol concentration increased (25 min: 0.34 ± 0.10 ng/mL < 55 min: 0.89 ± 0.07 ng/mL < 85 min: 1.27 ± 0.07 ng/mL; P < 0.0001), while EGF (P < 0.0001), IL-1ra (P < 0.0001), and IL-6 (P = 0.02) concentrations decreased over time. CONCLUSION Sweat analyte concentrations varied with time of sampling and anatomical region, which is essential information to consider when conducting future work in this area. CLINICAL TRIAL IDENTIFIER NCT04240951 registered January 27, 2020.
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Affiliation(s)
- Michelle A King
- Gatorade Sports Science Institute, PepsiCo R&D Life Sciences, Barrington, IL, USA
| | - Shyretha D Brown
- Gatorade Sports Science Institute, PepsiCo R&D Life Sciences, Barrington, IL, USA
| | - Kelly A Barnes
- Gatorade Sports Science Institute, PepsiCo R&D Life Sciences, Barrington, IL, USA
| | | | - Lindsay B Baker
- Gatorade Sports Science Institute, PepsiCo R&D Life Sciences, Barrington, IL, USA.
- Gatorade Sports Science Institute, PepsiCo R&D Life Sciences, Valhalla, NY, USA.
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Al Rudaisat M, Chen X, Chen S, Amanullah M, Wang X, Liang Q, Hua C, Zhou C, Song Y, van der Veen S, Cheng H. RNA sequencing and metabolic analysis of imiquimod-induced psoriasis-like mice with chronic restrain stress. Life Sci 2023:121788. [PMID: 37230377 DOI: 10.1016/j.lfs.2023.121788] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 04/25/2023] [Accepted: 05/15/2023] [Indexed: 05/27/2023]
Abstract
AIM Psoriasis is one of the most common dermatological disorders, characterized by increased epidermal hyperplasia and immune cell infiltration. Psychological stress has been reported to contribute to the severity, aggravation, and relapse of psoriasis. However, the exact mechanism involved in psychological stress's impact on psoriasis is still unclear. We aim to investigate the role of psychological stress in psoriasis from a transcriptomic and metabolomic perspective. MAIN METHOD We developed a chronic restrain stress (CRS)-imiquimod (IMQ)-induced psoriasis-like mouse model and performed a comprehensive comparative transcriptomic and metabolic analysis with control mice, CRS-treated mice, and IMQ-treated mice to investigate how psychological stress affects psoriasis. KEY FINDING We found that CRS-IMQ-induced psoriasis-like mice showed significant exacerbation of psoriasis-like skin inflammation compared with mice treated with IMQ only. Mice of the CRS + IMQ group showed increased expression of keratinocyte proliferation and differentiation genes, differential regulation of cytokines, and promotion of linoleic acid metabolism. Correlation analysis of differentially expressed genes in the CRS-IMQ-induced psoriasis-like mice and human psoriasis datasets compared with respective controls revealed 96 overlapping genes of which 30 genes showed consistent induced or repressed expression in all human and mouse datasets. SIGNIFICANCE Our study provides new insights into the effects of psychological stress on psoriasis pathogenesis and the mechanisms involved, which provides clues for development of therapeutics or biomarkers.
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Affiliation(s)
- Mus'ab Al Rudaisat
- Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China
| | - Xianzhen Chen
- Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China
| | - Siji Chen
- Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China
| | - Md Amanullah
- Institute of Translational Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China
| | - Xuewen Wang
- Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China
| | - Qichang Liang
- Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China
| | - Chunting Hua
- Institute of Translational Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China
| | - Can Zhou
- Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China
| | - Yinjing Song
- Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China
| | - Stijn van der Veen
- Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China; Department of Microbiology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, Hangzhou 310000, China.
| | - Hao Cheng
- Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China.
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Heart Rate Variability in Subjects with Severe Allergic Background Undergoing COVID-19 Vaccination. Vaccines (Basel) 2023; 11:vaccines11030567. [PMID: 36992151 DOI: 10.3390/vaccines11030567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 02/21/2023] [Accepted: 02/25/2023] [Indexed: 03/05/2023] Open
Abstract
Anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination is the world’s most important strategy for stopping the pandemic. Vaccination challenges the body’s immune response and can be complicated by hypersensitivity reactions. The autonomic nervous system can modulate the inflammatory immune response, therefore constituting a potential marker to characterize individuals at high risk of hypersensitivity reactions. Autonomic nervous system functionality was assessed through measurement of the heart rate variability (HRV) in subjects with a history of severe allergic reactions and 12 control subjects. HRV parameters included the mean electrocardiograph RR interval and the standard deviation of all normal R–R intervals (SDNN). All measurements were performed immediately before the anti-SARS-CoV-2 vaccination. The median RR variability was lower in the study than in the control group: 687 ms (645–759) vs. 821 ms (759–902); p = 0.02. The SDNN was lower in the study group than in the control group: 32 ms (23–36) vs. 50 ms (43–55); p < 0.01. No correlation was found between age and the SDNN. Autonomic nervous system activity is unbalanced in people with a severe allergy background.
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Stamou MI, Colling C, Dichtel LE. Adrenal aging and its effects on the stress response and immunosenescence. Maturitas 2023; 168:13-19. [PMID: 36370489 PMCID: PMC10426230 DOI: 10.1016/j.maturitas.2022.10.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 10/14/2022] [Accepted: 10/20/2022] [Indexed: 11/06/2022]
Abstract
Normal aging is linked to various endocrine gland changes, including changes in the adrenal glands. Aging is linked to alterations of the hypothalamic-pituitary-adrenal (HPA) axis, including an increase in cortisol levels, a disruption of the negative cortisol feedback, and attenuation of cortisol's diurnal pattern. In addition, secretion of aldosterone and adrenal androgens [dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS)] from the adrenal cortex decreases with aging. In this review, we describe normal adrenal function, the adrenal response to stress and immunomodulation in aging individuals as well as the effects of adrenal aging on body composition, metabolic profile, bone health and cognition.
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Affiliation(s)
- Maria I Stamou
- Endocrine Division, Massachusetts General Hospital, Boston, MA, USA.
| | - Caitlin Colling
- Endocrine Division, Massachusetts General Hospital, Boston, MA, USA
| | - Laura E Dichtel
- Endocrine Division, Massachusetts General Hospital, Boston, MA, USA
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11
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Oaks BM, Adu-Afarwuah S, Ashorn P, Lartey A, Laugero KD, Okronipa H, Stewart CP, Dewey KG. Increased risk of preterm delivery with high cortisol during pregnancy is modified by fetal sex: a cohort study. BMC Pregnancy Childbirth 2022; 22:727. [PMID: 36151538 PMCID: PMC9502964 DOI: 10.1186/s12884-022-05061-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 09/13/2022] [Indexed: 11/10/2022] Open
Abstract
Background Previous studies show an association between maternal plasma and salivary cortisol and preterm birth but have been primarily conducted in high-income countries. It is unknown whether salivary cortisol is a risk factor for preterm birth in Ghana. Our objective was to determine whether maternal salivary cortisol during pregnancy was associated with pregnancy duration and preterm delivery in Ghana. Methods We conducted a cohort study of 783 pregnant women in Ghana. We measured salivary cortisol at baseline (mean 16 wk), 28 wk., and 36 wk. gestation. Pregnancy duration was determined primarily by ultrasound. We used adjusted linear regression models to examine the association between cortisol and pregnancy duration and Poisson regression models to determine the risk of preterm delivery among women with high cortisol at baseline or 28 wk. gestation. Results Mean pregnancy duration was 39.4 ± 1.8 wk. and 6.6% had a preterm delivery. Mean maternal cortisol increased throughout pregnancy, from 4.9 ± 2.7 nmol/L at baseline (16 wk) to 6.4 ± 3.2 nmol/L at 28 wk. and 7.9 ± 3.0 nmol/L at 36 wk. gestation. In adjusted analyses, higher cortisol concentrations at baseline (β = − 0.39, p = .002) and 28 wk. (β = − 0.49, p = .001), but not 36 wk. (β = − 0.23, p = .084) were associated with a shorter pregnancy duration. Women with high cortisol at baseline (> 6.3 nmol/L) had an increased relative risk of preterm delivery (RR (95% CI): 1.96 (1.13, 3.40)), but the association between high cortisol at 28 wk. and preterm delivery was not significant. There was a significant interaction with fetal sex (p-for-interaction = 0.037): among women carrying male fetuses, high cortisol at baseline increased the risk of preterm delivery threefold (3.18 (1.51, 6.71)) while there was no association (1.17 (0.50, 2.74)) among women carrying female fetuses. Conclusion Higher maternal cortisol is associated with a shorter pregnancy duration and an increased risk of preterm delivery. Subgroup analysis by fetal sex revealed that this association is evident primarily among women carrying male fetuses. Future studies of cortisol and preterm delivery should include consideration of fetal sex as a potential effect modifier. Supplementary Information The online version contains supplementary material available at 10.1186/s12884-022-05061-8.
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Affiliation(s)
- Brietta M Oaks
- Department of Nutrition and Food Sciences, University of Rhode Island, Kingston, RI, 02881, USA.
| | - Seth Adu-Afarwuah
- Department of Nutrition and Food Science, University of Ghana, Accra, Ghana
| | - Per Ashorn
- Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health, Technology, Tampere University, Tampere, Finland.,Department of Pediatrics, Tampere University Hospital, Tampere, Finland
| | - Anna Lartey
- Department of Nutrition and Food Science, University of Ghana, Accra, Ghana
| | - Kevin D Laugero
- USDA Western Human Nutrition Research Center, Davis, CA, USA.,Department of Nutrition, University of California, Davis, CA, USA
| | - Harriet Okronipa
- Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA
| | | | - Kathryn G Dewey
- Department of Nutrition, University of California, Davis, CA, USA
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12
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Martinez GJ, Grover T, Mattingly SM, Mark G, D'Mello S, Aledavood T, Akbar F, Robles-Granda P, Striegel A. Alignment Between Heart Rate Variability From Fitness Trackers and Perceived Stress: Perspectives From a Large-Scale In Situ Longitudinal Study of Information Workers. JMIR Hum Factors 2022; 9:e33754. [PMID: 35925662 PMCID: PMC9389384 DOI: 10.2196/33754] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 06/09/2022] [Accepted: 06/13/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Stress can have adverse effects on health and well-being. Informed by laboratory findings that heart rate variability (HRV) decreases in response to an induced stress response, recent efforts to monitor perceived stress in the wild have focused on HRV measured using wearable devices. However, it is not clear that the well-established association between perceived stress and HRV replicates in naturalistic settings without explicit stress inductions and research-grade sensors. OBJECTIVE This study aims to quantify the strength of the associations between HRV and perceived daily stress using wearable devices in real-world settings. METHODS In the main study, 657 participants wore a fitness tracker and completed 14,695 ecological momentary assessments (EMAs) assessing perceived stress, anxiety, positive affect, and negative affect across 8 weeks. In the follow-up study, approximately a year later, 49.8% (327/657) of the same participants wore the same fitness tracker and completed 1373 EMAs assessing perceived stress at the most stressful time of the day over a 1-week period. We used mixed-effects generalized linear models to predict EMA responses from HRV features calculated over varying time windows from 5 minutes to 24 hours. RESULTS Across all time windows, the models explained an average of 1% (SD 0.5%; marginal R2) of the variance. Models using HRV features computed from an 8 AM to 6 PM time window (namely work hours) outperformed other time windows using HRV features calculated closer to the survey response time but still explained a small amount (2.2%) of the variance. HRV features that were associated with perceived stress were the low frequency to high frequency ratio, very low frequency power, triangular index, and SD of the averages of normal-to-normal intervals. In addition, we found that although HRV was also predictive of other related measures, namely, anxiety, negative affect, and positive affect, it was a significant predictor of stress after controlling for these other constructs. In the follow-up study, calculating HRV when participants reported their most stressful time of the day was less predictive and provided a worse fit (R2=0.022) than the work hours time window (R2=0.032). CONCLUSIONS A significant but small relationship between perceived stress and HRV was found. Thus, although HRV is associated with perceived stress in laboratory settings, the strength of that association diminishes in real-life settings. HRV might be more reflective of perceived stress in the presence of specific and isolated stressors and research-grade sensing. Relying on wearable-derived HRV alone might not be sufficient to detect stress in naturalistic settings and should not be considered a proxy for perceived stress but rather a component of a complex phenomenon.
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Affiliation(s)
- Gonzalo J Martinez
- Computer Science and Engineering, University of Notre Dame, Notre Dame, IN, United States
| | - Ted Grover
- Informatics Department, University of California, Irvine, CA, United States
| | - Stephen M Mattingly
- Computer Science and Engineering, University of Notre Dame, Notre Dame, IN, United States
| | - Gloria Mark
- Informatics Department, University of California, Irvine, CA, United States
| | - Sidney D'Mello
- Institute of Cognitive Science, University of Colorado Boulder, Boulder, CO, United States
| | | | - Fatema Akbar
- Informatics Department, University of California, Irvine, CA, United States
| | - Pablo Robles-Granda
- Thomas M Siebel Center for Computer Science, University of Illinois Urbana-Champaign, Urbana, IL, United States
| | - Aaron Striegel
- Computer Science and Engineering, University of Notre Dame, Notre Dame, IN, United States
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13
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Kussainova A, Kassym L, Bekenova N, Akhmetova A, Glushkova N, Kussainov A, Urazalina Z, Yurkovskaya O, Smail Y, Pak L, Semenova Y. Gene polymorphisms and serum levels of BDNF and CRH in vitiligo patients. PLoS One 2022; 17:e0271719. [PMID: 35905107 PMCID: PMC9337645 DOI: 10.1371/journal.pone.0271719] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Accepted: 06/28/2022] [Indexed: 11/19/2022] Open
Abstract
Background Vitiligo is one of the most common hypomelanoses, in which the destruction of functioning melanocytes causes depigmentation of the skin, hair and mucous membranes. The genes encrypting brain-derived neurotrophic factor (BDNF) and corticotropin releasing hormone (CRH) might be the conceivable contributors to the development of vitiligo. This study was aimed at investigation of the serum levels of BDNF and CRH as well as their selected single nucleotide polymorphisms (SNPs) in vitiligo patients in comparison with the healthy controls. Methods The cross-sectional study was carried out between October 2020 and June 2021 in 93 vitiligo patients (age range from 23 to 48 years) and 132 healthy controls (age range from 24 to 52 years). The psychological status of study participants was evaluated using the Generalized Anxiety Disorder-7 (GAD-7) scale. Serum levels of BDNF and CRH were measured with the help of a commercially available sandwich enzyme-linked immunosorbent assay (ELISA) kit. Genotyping for the rs11030094 polymorphism of the BDNF gene and for the rs242924 polymorphism of the corticotropin releasing hormone receptor 1 (CRH-R1) gene was performed by a real-time polymerase chain reaction (PCR). Results There was a significant relationship between the CRH-R1 rs242924 and BDNF rs11030094 polymorphisms and vitiligo. Moreover, serum levels of neurotransmitters differed significantly between vitiligo and control groups and were associated with the CRH-R1 rs242924 and BDNF rs11030094 SNPs. Conclusions Our findings demonstrated the association between CRH-R1 rs242924 and BDNF rs11030094 polymorphisms and vitiligo. Further studies need to be carried out in vitiligo patients to confirm the results observed.
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Affiliation(s)
- Assiya Kussainova
- Department of Dermatovenerology and Cosmetology, NJSC "Semey Medical University", Semey, Republic of Kazakhstan
| | - Laura Kassym
- School of Medicine, Nazarbayev University, Nur-Sultan, Republic of Kazakhstan
- * E-mail:
| | - Nazira Bekenova
- Department of Dermatovenerology and Cosmetology, NJSC "Semey Medical University", Semey, Republic of Kazakhstan
| | - Almira Akhmetova
- Department of Dermatovenerology and Cosmetology, NJSC "Semey Medical University", Semey, Republic of Kazakhstan
| | - Natalya Glushkova
- Department of Epidemiology, Biostatistics & Evidence Based Medicine, Al-Farabi Kazakh National University, Almaty, Republic of Kazakhstan
| | - Almas Kussainov
- Department of Psychiatry and Narcology, NJSC "Astana Medical University", Nur-Sultan, Republic of Kazakhstan
| | - Zhanar Urazalina
- Department of Emergency Medicine, NJSC "Semey Medical University", Semey, Republic of Kazakhstan
| | - Oxana Yurkovskaya
- Department of Personalized Medicine, NJSC "Semey Medical University", Semey, Republic of Kazakhstan
| | - Yerbol Smail
- Department of Infectious Diseases and Immunology, NJSC "Semey Medical University", Semey, Republic of Kazakhstan
| | - Laura Pak
- Department of Clinical Oncology and Nuclear Medicine, NJSC "Semey Medical University", Semey, Republic of Kazakhstan
| | - Yuliya Semenova
- Department of Neurology, Ophthalmology, Otorhinolaryngology, NJSC "Semey Medical University", Semey, Republic of Kazakhstan
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14
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Musana J, Cohen CR, Kuppermann M, Gerona R, Wanyoro A, Aguilar D, Santos N, Temmerman M, Weiss SJ. Obstetric risk in pregnancy interacts with hair cortisone levels to reduce gestational length. Front Glob Womens Health 2022; 3:878538. [PMID: 35936818 PMCID: PMC9354598 DOI: 10.3389/fgwh.2022.878538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 06/30/2022] [Indexed: 11/29/2022] Open
Abstract
Background Maternal psychological stress has been linked to preterm birth. However, the differential contribution of psychological stress versus stress hormones is not clear. Studies focus primarily on perceived stress and cortisol, with few assessing its inter-convertible hormone cortisone. Furthermore, little is known about the potential moderating roles of obstetric risk and fetal sex in the relationship between maternal stress and gestational length. This gap in knowledge is particularly evident for rural women who typically experience chronic multiple stressors during pregnancy. We explored the relationship of hormonal and psychological stress to gestational length and the effects of obstetric risks and fetal sex on this relationship among Kenyan pregnant women. Methods The sample included 130 women recruited between 22 to 28 weeks gestation. They completed a clinical and sociodemographic questionnaire together with the Perceived Stress Scale and provided a hair sample for cortisol and cortisone assay. Women underwent an ultrasound to assess weeks of gestation. At delivery, their pregnancy-related health problems were identified using information extracted from medical records to compile each woman's number of pregnancy risks on the Obstetric Medical Risk Index (OMRI). Results Perceived stress and hair cortisol were not significant predictors of gestational length. However, a greater number of obstetric risks on the OMRI was associated with shorter gestational length. This effect was further explained by the interaction between obstetric risk and hair cortisone (B = 0.709, p = 0.02). Hair cortisone levels of mothers who had a shorter gestation were significantly higher in mothers with 2 or more risks on the OMRI but not among mothers with only one or no risks (t = 2.39, p = 0.02). Fetal sex had no relationship to gestational length and also had no moderating effect on the relationship between any stress-related metric and gestational length. Conclusion Cortisone levels may increase in anticipation of shorter gestation as a compensatory response to increased obstetric risk. Elevated cortisone may be a more sensitive marker of risk for early delivery than cortisol or psychological stress, with salience for both the male and female fetus.
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Affiliation(s)
- Joseph Musana
- Department of Obstetrics and Gynaecology, Aga Khan University Hospital, Nairobi, Kenya
- *Correspondence: Joseph Musana
| | - Craig R. Cohen
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA, United States
| | - Miriam Kuppermann
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA, United States
| | - Roy Gerona
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA, United States
| | - Anthony Wanyoro
- Department of Obstetrics and Gynaecology, Kenyatta University, Nairobi, Kenya
| | - David Aguilar
- Clinical Toxicology and Environmental Biomonitoring Lab, University of California, San Francisco, San Francisco, CA, United States
| | - Nicole Santos
- Institute for Global Health Sciences, University of California, San Francisco, San Francisco, CA, United States
| | - Marleen Temmerman
- Department of Obstetrics and Gynaecology, Aga Khan University Hospital, Nairobi, Kenya
| | - Sandra J. Weiss
- Department of Community Health Systems, University of California, San Francisco, San Francisco, CA, United States
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15
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Korkmaz C, Cansu DÜ, Cansu GB. A Hypothesis Regarding Neurosecretory Inhibition of Stress Mediators by Colchicine in Preventing Stress-Induced Familial Mediterranean Fever Attacks. Front Immunol 2022; 13:834769. [PMID: 35251026 PMCID: PMC8891608 DOI: 10.3389/fimmu.2022.834769] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 01/31/2022] [Indexed: 12/31/2022] Open
Abstract
Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disease characterized by recurrent episodes of fever and serositis. Colchicine (Col) has a crucial role in the prevention of amyloidosis and FMF attacks. The effect of Col on innate immune cells is based on the inhibition of the microtubule system. The microtubule system is also very important for neurosecretory functions. The inhibitory effect of Col on neurosecretory functions is an overlooked issue. Considering that the neuroimmune cross-talk process plays a role in the development of inflammatory diseases, the effect of Col on the neuronal system becomes important. FMF attacks are related to emotional stress. Therefore, the effect of Col on stress mediators is taken into consideration. In this hypothetical review, we discuss the possible effects of Col on the central nervous systems (CNS) and peripheral nervous systems (PNS) in light of mostly experimental study findings using animal models. Studies to be carried out on this subject will shed light on the pathogenesis of FMF attacks and the other possible mechanisms of action of Col apart from the anti-inflammatory features.
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Affiliation(s)
- Cengiz Korkmaz
- Department of Internal Medicine, Division of Rheumatology, School of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey
| | - Döndü Üsküdar Cansu
- Department of Internal Medicine, Division of Rheumatology, School of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey
| | - Güven Barıs Cansu
- Department of Endocrinology, School of Medicine, Kutahya Health Science University, Kutahya, Turkey
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16
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Mishra A, Wang Y, Yin F, Vitali F, Rodgers KE, Soto M, Mosconi L, Wang T, Brinton RD. A tale of two systems: Lessons learned from female mid-life aging with implications for Alzheimer's prevention & treatment. Ageing Res Rev 2022; 74:101542. [PMID: 34929348 PMCID: PMC8884386 DOI: 10.1016/j.arr.2021.101542] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 12/05/2021] [Accepted: 12/13/2021] [Indexed: 02/03/2023]
Abstract
Neurological aging is frequently viewed as a linear process of decline, whereas in reality, it is a dynamic non-linear process. The dynamic nature of neurological aging is exemplified during midlife in the female brain. To investigate fundamental mechanisms of midlife aging that underlie risk for development of Alzheimer's disease (AD) in late life, we investigated the brain at greatest risk for the disease, the aging female brain. Outcomes of our research indicate that mid-life aging in the female is characterized by the emergence of three phases: early chronological (pre-menopause), endocrinological (peri-menopause) and late chronological (post-menopause) aging. The endocrinological aging program is sandwiched between early and late chronological aging. Throughout the three stages of midlife aging, two systems of biology, metabolic and immune, are tightly integrated through a network of signaling cascades. The network of signaling between these two systems of biology underlie an orchestrated sequence of adaptative starvation responses that shift the brain from near exclusive dependence on a single fuel, glucose, to utilization of an auxiliary fuel derived from lipids, ketone bodies. The dismantling of the estrogen control of glucose metabolism during mid-life aging is a critical contributor to the shift in fuel systems and emergence of dynamic neuroimmune phenotype. The shift in fuel reliance, puts the largest reservoir of local fatty acids, white matter, at risk for catabolism as a source of lipids to generate ketone bodies through astrocytic beta oxidation. APOE4 genotype accelerates the tipping point for emergence of the bioenergetic crisis. While outcomes derived from research conducted in the female brain are not directly translatable to the male brain, the questions addressed in a female centric program of research are directly applicable to investigation of the male brain. Like females, males with AD exhibit deficits in the bioenergetic system of the brain, activation of the immune system and hallmark Alzheimer's pathologies. The drivers and trajectory of mechanisms underlying neurodegeneration in the male brain will undoubtedly share common aspects with the female in addition to factors unique to the male. Preclinical and clinical evidence indicate that midlife endocrine aging can also be a transitional bridge to autoimmune disorders. Collectively, the data indicate that endocrinological aging is a critical period "tipping point" in midlife which can initiate emergence of the prodromal stage of late-onset-Alzheimer's disease. Interventions that target both immune and metabolic shifts that occur during midlife aging have the potential to alter the trajectory of Alzheimer's risk in late life. Further, to achieve precision medicine for AD, chromosomal sex is a critical variable to consider along with APOE genotype, other genetic risk factors and stage of disease.
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Affiliation(s)
- Aarti Mishra
- Center for Innovation in Brain Science, University of Arizona, Tucson, AZ 85719, USA
| | - Yiwei Wang
- Center for Innovation in Brain Science, University of Arizona, Tucson, AZ 85719, USA
| | - Fei Yin
- Center for Innovation in Brain Science, University of Arizona, Tucson, AZ 85719, USA
| | - Francesca Vitali
- Center for Innovation in Brain Science, University of Arizona, Tucson, AZ 85719, USA
| | - Kathleen E Rodgers
- Center for Innovation in Brain Science, University of Arizona, Tucson, AZ 85719, USA
| | - Maira Soto
- Center for Innovation in Brain Science, University of Arizona, Tucson, AZ 85719, USA
| | - Lisa Mosconi
- Department of Neurology, Weill Cornell Medicine, New York, NY 10021, USA
| | - Tian Wang
- Center for Innovation in Brain Science, University of Arizona, Tucson, AZ 85719, USA
| | - Roberta D Brinton
- Center for Innovation in Brain Science, University of Arizona, Tucson, AZ 85719, USA.
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17
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Reddy V, McCarthy M, Raval AP. Xenoestrogens impact brain estrogen receptor signaling during the female lifespan: A precursor to neurological disease? Neurobiol Dis 2021; 163:105596. [PMID: 34942334 DOI: 10.1016/j.nbd.2021.105596] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 12/08/2021] [Accepted: 12/18/2021] [Indexed: 02/07/2023] Open
Abstract
Xenoestrogens, foreign synthetic chemicals mimicking estrogens, are lurking in our surroundings. Climate change may alter their toxicity and bioavailability. Since xenoestrogens have extremely high lipid solubility and are structurally similar to natural endogenous estrogens, they can bind to estrogen receptors (ERs) -alpha (ER-α) and -beta (ER-β). Scientific evidence accumulated over the past decades have suggested that natural 17β-estradiol (E2; a potent estrogen), via activation of its receptors, plays a pivotal role in regulation of brain development, differentiation, metabolism, synaptic plasticity, neuroprotection, cognition, anxiety, body temperature, feeding and sexual behavior. In the brain, ER-β is predominantly expressed in the various regions, including cerebral cortex and hippocampus, that have been shown to play a key role in cognition. Therefore, disturbances in function of ER-β mediated E2 signaling by xenoestrogens can lead to deleterious effects that potentiate a variety of neurological diseases starting from prenatal to post-menopause in women. The goal of this review is to identify the possible neurological effects of xenoestrogens that can alter estrogen receptor-mediated signaling in the brain during different stages of the female lifespan.
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Affiliation(s)
- Varun Reddy
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA; Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA
| | - Micheline McCarthy
- Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA
| | - Ami P Raval
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA; Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.
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18
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Arfuso F, Giudice E, Panzera M, Rizzo M, Fazio F, Piccione G, Giannetto C. Interleukin-1Ra (Il-1Ra) and serum cortisol level relationship in horse as dynamic adaptive response during physical exercise. Vet Immunol Immunopathol 2021; 243:110368. [PMID: 34922262 DOI: 10.1016/j.vetimm.2021.110368] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 12/07/2021] [Accepted: 12/09/2021] [Indexed: 12/29/2022]
Abstract
The monitoring of endocrine and immunologic markers during exercise is of paramount importance to assess and/or maintain the physical well-being of athletes as well as to optimize the athletic performance. This study aimed to investigate the linkage between acute stress response and immune status in Thoroughbred horses competing in an official 1300-m race. From 10 horses blood was collected 1 week before the day of the race (1W-BEFORE), before (REST) and immediately after the race to assess the cortisol, Interleukin-1 receptor antagonist (IL-1Ra), total proteins, white blood cells (WBC), red blood cells (RBC), haemoglobin (Hb) and haematocrit (Hct) concentration. Higher levels of cortisol, Il-1Ra, WBC and erythrocytes indices after exercise was found than 1W-BEFORE and REST (P < 0.0001). Cortisol concentration was positively correlated with Il-1Ra, WBC, RBC, Hb and Hct. Overall, the findings suggest that submaximal exercise induces an acute stress response and an immune system reaction in athletic horse. Also, the correlation found between cortisol levels and Il-1Ra, WBC and erythrocytes indices open new scenario on the positive role of this hormone on the complex and dynamic physiological adaptation to exercise implemented by the organism to re-establish the homeostatic equilibrium, and, interestingly, to maintain an adequate anti-inflammatory environment after exercise.
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Affiliation(s)
- Francesca Arfuso
- Department of Veterinary Sciences, University of Messina, Polo Universitario dell'Annunziata, 98168, Messina, Italy.
| | - Elisabetta Giudice
- Department of Veterinary Sciences, University of Messina, Polo Universitario dell'Annunziata, 98168, Messina, Italy
| | - Michele Panzera
- Department of Veterinary Sciences, University of Messina, Polo Universitario dell'Annunziata, 98168, Messina, Italy
| | - Maria Rizzo
- Department of Veterinary Sciences, University of Messina, Polo Universitario dell'Annunziata, 98168, Messina, Italy
| | - Francesco Fazio
- Department of Veterinary Sciences, University of Messina, Polo Universitario dell'Annunziata, 98168, Messina, Italy
| | - Giuseppe Piccione
- Department of Veterinary Sciences, University of Messina, Polo Universitario dell'Annunziata, 98168, Messina, Italy
| | - Claudia Giannetto
- Department of Veterinary Sciences, University of Messina, Polo Universitario dell'Annunziata, 98168, Messina, Italy
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19
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Rodriguez Bauza DE, Silveyra P. Asthma, atopy, and exercise: Sex differences in exercise-induced bronchoconstriction. Exp Biol Med (Maywood) 2021; 246:1400-1409. [PMID: 33794694 DOI: 10.1177/15353702211003858] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Asthma is a chronic inflammatory lung disease affecting approximately 7.7% of the US population. Sex differences in the prevalence, incidence, and severity of asthma have been widely described throughout the lifespan, showing higher rates in boys than girls before puberty, but a reversed pattern in adults. Asthma is often associated with atopy, i.e. the tendency to develop allergic diseases, and can be worsened by environmental stimuli and/or exercise. While not exclusive to patients with asthma, exercise-induced bronchoconstriction (EIB) is a common complication of athletes and individuals who exercise regularly. Currently, there is limited research on sex differences in EIB and its relationship with atopy and asthma in men and women. In this minireview, we summarize the available literature on this topic. Overall, the collective knowledge supports the notion that physiological changes triggered during exercise affect males and females differently, suggesting an interaction among sex, exercise, sex hormones, and atopic status in the course of EIB pathophysiology. Understanding these differences is important to provide personalized management plans to men and women who exercise regularly and suffer from underlying asthma and/or atopy.
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Affiliation(s)
| | - Patricia Silveyra
- Biobehavioral Laboratory, The University of North Carolina at Chapel Hill, School of Nursing, Chapel Hill, NC 27599, USA.,Department of Environmental and Occupational Health, Indiana University School of Public Health, Bloomington, IN 47405, USA
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20
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Mussa BM, Srivastava A, Verberne AJM. COVID-19 and Neurological Impairment: Hypothalamic Circuits and Beyond. Viruses 2021; 13:v13030498. [PMID: 33802995 PMCID: PMC8002703 DOI: 10.3390/v13030498] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 02/15/2021] [Accepted: 02/26/2021] [Indexed: 12/23/2022] Open
Abstract
In December 2019, a novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, the capital of Hubei, China. The virus infection, coronavirus disease 2019 (COVID-19), represents a global concern, as almost all countries around the world are affected. Clinical reports have confirmed several neurological manifestations in COVID-19 patients such as headaches, vomiting, and nausea, indicating the involvement of the central nervous system (CNS) and peripheral nervous system (PNS). Neuroinvasion of coronaviruses is not a new phenomenon, as it has been demonstrated by previous autopsies of severe acute respiratory syndrome coronavirus (SARS-CoV) patients who experienced similar neurologic symptoms. The hypothalamus is a complex structure that is composed of many nuclei and diverse neuronal cell groups. It is characterized by intricate intrahypothalamic circuits that orchestrate a finely tuned communication within the CNS and with the PNS. Hypothalamic circuits are critical for maintaining homeostatic challenges including immune responses to viral infections. The present article reviews the possible routes and mechanisms of neuroinvasion of SARS-CoV-2, with a specific focus on the role of the hypothalamic circuits in mediating the neurological symptoms noted during COVID-19 infection.
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Affiliation(s)
- Bashair M. Mussa
- Basic Medical Science Department, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
- Correspondence: ; Tel.: +971-65057220
| | - Ankita Srivastava
- Sharjah Institute for Medical Research and College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates;
| | - Anthony J. M. Verberne
- Department of Medicine, Austin Health, University of Melbourne, Heidelberg 3084, Australia;
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21
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Brauer VS, Zambuzi FA, Espíndola MS, Cavalcanti Neto MP, Prado MKB, Cardoso PM, Soares LS, Galvao-Lima LJ, Leopoldino AM, Cardoso CRDB, Frantz FG. The influence of dehydroepiandrosterone on effector functions of neutrophils. BRAZ J PHARM SCI 2021. [DOI: 10.1590/s2175-97902020000419139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
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22
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Mahmood Z, Davidsson A, Olsson E, Leanderson P, Lundberg AK, Jonasson L. The effect of acute exercise on interleukin-6 and hypothalamic-pituitary-adrenal axis responses in patients with coronary artery disease. Sci Rep 2020; 10:21390. [PMID: 33288784 PMCID: PMC7721799 DOI: 10.1038/s41598-020-78286-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 11/18/2020] [Indexed: 12/02/2022] Open
Abstract
Vulnerability to stress-induced inflammation has been linked to a dysfunctional hypothalamus-pituitary-adrenal (HPA) axis. In the present study, patients with known or suspected coronary artery disease (CAD) were assessed with respect to inflammatory and HPA axis response to acute physical exercise. An exercise stress test was combined with SPECT myocardial perfusion imaging. Plasma and saliva samples were collected before and 30 min after exercise. Interleukin (IL)-6 and adrenocorticotropic hormone (ACTH) were measured in plasma, while cortisol was measured in both plasma and saliva. In total, 124 patients were included of whom 29% had a prior history of CAD and/or a myocardial perfusion deficit. The levels of exercise intensity and duration were comparable in CAD and non-CAD patients. However, in CAD patients, IL-6 increased after exercise (p = 0.019) while no differences were seen in HPA axis variables. Conversely, patients without CAD exhibited increased levels of ACTH (p = 0.003) and cortisol (p = 0.004 in plasma, p = 0.006 in saliva), but no change in IL-6. We conclude that the IL-6 response to acute physical exercise is exaggerated in CAD patients and may be out of balance due to HPA axis hypoactivity. It remains to be further investigated whether this imbalance is a potential diagnostic and therapeutic target in CAD.
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Affiliation(s)
- Zeid Mahmood
- Unit of Cardiovascular Medicine, Department of Clinical Physiology in Linköping and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Anette Davidsson
- Unit of Cardiovascular Medicine, Department of Clinical Physiology in Linköping and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Eva Olsson
- Unit of Cardiovascular Medicine, Department of Clinical Physiology in Linköping and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Per Leanderson
- Unit of Clinical Medicine, Occupational and Environmental Medicine Center, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Anna K Lundberg
- Unit of Cardiovascular Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Lena Jonasson
- Unit of Cardiovascular Medicine, Department of Cardiology in Linköping, and Department of Health, Medicine and Caring Sciences, Linköping University Hospital, Linköping University, 581 85, Linköping, Sweden.
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McCarthy M, Raval AP. The peri-menopause in a woman's life: a systemic inflammatory phase that enables later neurodegenerative disease. J Neuroinflammation 2020; 17:317. [PMID: 33097048 PMCID: PMC7585188 DOI: 10.1186/s12974-020-01998-9] [Citation(s) in RCA: 109] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Accepted: 10/14/2020] [Indexed: 02/08/2023] Open
Abstract
The peri-menopause or menopausal transition—the time period that surrounds the final years of a woman’s reproductive life—is associated with profound reproductive and hormonal changes in a woman’s body and exponentially increases a woman’s risk of cerebral ischemia and Alzheimer’s disease. Although our understanding of the exact timeline or definition of peri-menopause is limited, it is clear that there are two stages to the peri-menopause. These are the early menopausal transition, where menstrual cycles are mostly regular, with relatively few interruptions, and the late transition, where amenorrhea becomes more prolonged and lasts for at least 60 days, up to the final menstrual period. Emerging evidence is showing that peri-menopause is pro-inflammatory and disrupts estrogen-regulated neurological systems. Estrogen is a master regulator that functions through a network of estrogen receptors subtypes alpha (ER-α) and beta (ER-β). Estrogen receptor-beta has been shown to regulate a key component of the innate immune response known as the inflammasome, and it also is involved in regulation of neuronal mitochondrial function. This review will present an overview of the menopausal transition as an inflammatory event, with associated systemic and central nervous system inflammation, plus regulation of the innate immune response by ER-β-mediated mechanisms.
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Affiliation(s)
- Micheline McCarthy
- Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA
| | - Ami P Raval
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory, Leonard M. Miller School of Medicine, University of Miami, 1420 NW 9th Avenue, Neurology Research Building, Room # 203H, Miami, FL, 33136, USA. .,Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.
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24
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Xu Z, Wei Y, Guo S, Lin D, Ye H. B-type allatostatin modulates immune response in hepatopancreas of the mud crab Scylla paramamosain. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2020; 110:103725. [PMID: 32376281 DOI: 10.1016/j.dci.2020.103725] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 04/28/2020] [Accepted: 04/28/2020] [Indexed: 06/11/2023]
Abstract
B-type allatostatin (AST-B) is a pleiotropic neuropeptide, widely found in arthropods. However, the information about its immune effect in crustaceans is unknown. In this study, we identified the nervous tissue as the main site for Sp-AST-B expression, while its receptor gene (Sp-AST-BR) is widely expressed in various tissues, including the hepatopancreas. This suggests the peptide's potential role in diverse physiological processes in the mud crab Scylla paramamosain. In situ hybridization revealed that Sp-AST-BR is mainly localized in the F-cell of hepatopancreas. Furthermore, we found a significant up-regulation of Sp-AST-BR transcripts in the hepatopancreas following exposure to lipopolysaccharide (LPS) or polyriboinosinic polyribocytidylic acid (Poly (I:C)). Results from in vitro and in vivo experiments revealed that treatment with a synthetic AST-B peptide mediated significant upregulation in expression of AST-BR, nuclear factor-κB (NF-κB) pathway components (Dorsal and Relish), pro-inflammatory cytokine (IL-16) and antimicrobial peptides (AMPs) in the hepatopancreas. In addition, AST-B treatment mediated significant elevation of nitric oxide (NO) production and enhanced the bacteriostasis capacity of the hepatopancreas tissue in vitro. Taken together, these findings reveal the existence of a basic neuroendocrine-immune (NEI) network in crabs, and indicate that AST-B could couple with its receptor to trigger downstream signaling pathways and induce immune responses in the hepatopancreas.
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Affiliation(s)
- Zhanning Xu
- College of Ocean and Earth Sciences, Xiamen University, Xiamen 361102, China
| | - Yujie Wei
- College of Ocean and Earth Sciences, Xiamen University, Xiamen 361102, China
| | - Songlin Guo
- Fisheries College, Jimei University, Xiamen, 361021, China
| | - Dongdong Lin
- College of Ocean and Earth Sciences, Xiamen University, Xiamen 361102, China
| | - Haihui Ye
- College of Ocean and Earth Sciences, Xiamen University, Xiamen 361102, China.
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25
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Rizzi A, Saccia M, Benagiano V. Is the Cerebellum Involved in the Nervous Control of the Immune System Function? Endocr Metab Immune Disord Drug Targets 2019; 20:546-557. [PMID: 31729296 DOI: 10.2174/1871530319666191115144105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 09/30/2019] [Accepted: 10/10/2019] [Indexed: 11/22/2022]
Abstract
BACKGROUND According to the views of psychoneuroendocrinoimmunology, many interactions exist between nervous, endocrine and immune system the purpose of which is to achieve adaptive measures restoring an internal equilibrium (homeostasis) following stress conditions. The center where these interactions converge is the hypothalamus. This is a center of the autonomic nervous system that controls the visceral systems, including the immune system, through both the nervous and neuroendocrine mechanisms. The nervous mechanisms are based on nervous circuits that bidirectionally connect hypothalamic neurons and neurons of the sympathetic and parasympathetic system; the neuroendocrine mechanisms are based on the release by neurosecretory hypothalamic neurons of hormones that target the endocrine cells and on the feedback effects of the hormones secreted by these endocrine cells on the same hypothalamic neurons. Moreover, the hypothalamus is an important subcortical center of the limbic system that controls through nervous and neuroendocrine mechanisms the areas of the cerebral cortex where the psychic functions controlling mood, emotions, anxiety and instinctive behaviors take place. Accordingly, various studies conducted in the last decades have indicated that hypothalamic diseases may be associated with immune and/or psychic disorders. OBJECTIVE Various researches have reported that the hypothalamus is controlled by the cerebellum through a feedback nervous circuit, namely the hypothalamocerebellar circuit, which bi-directionally connects regions of the hypothalamus, including the immunoregulatory ones, and related regions of the cerebellum. An objective of the present review was to analyze the anatomical bases of the nervous and neuroendocrine mechanisms for the control of the immune system and, in particular, of the interaction between hypothalamus and cerebellum to achieve the immunoregulatory function. CONCLUSION Since the hypothalamus represents the link through which the immune functions may influence the psychic functions and vice versa, the cerebellum, controlling several regions of the hypothalamus, could be considered as a primary player in the regulation of the multiple functional interactions postulated by psychoneuroendocrinoimmunology.
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Affiliation(s)
- Anna Rizzi
- Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari, Policlinico, Piazza Giulio Cesare, 70124 Bari, Italy
| | - Matteo Saccia
- Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari, Policlinico, Piazza Giulio Cesare, 70124 Bari, Italy
| | - Vincenzo Benagiano
- Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari, Policlinico, Piazza Giulio Cesare, 70124 Bari, Italy
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26
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Wang F, Li S, Xiang J, Li F. Transcriptome analysis reveals the activation of neuroendocrine-immune system in shrimp hemocytes at the early stage of WSSV infection. BMC Genomics 2019; 20:247. [PMID: 30922216 PMCID: PMC6437892 DOI: 10.1186/s12864-019-5614-4] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Accepted: 03/14/2019] [Indexed: 02/08/2023] Open
Abstract
Background Functional communications between nervous, endocrine and immune systems are well established in both vertebrates and invertebrates. Circulating hemocytes act as fundamental players in this crosstalk, whose functions are conserved during the evolution of the main groups of metazoans. However, the roles of the neuroendocrine-immune (NEI) system in shrimp hemocytes during pathogen infection remain largely unknown. Results In this study, we sequenced six cDNA libraries prepared with hemocytes from Litopenaeus vannamei which were injected by WSSV (white spot syndrome virus) or PBS for 6 h using Illumina Hiseq 4000 platform. As a result, 3444 differentially expressed genes (DEGs), including 3240 up-regulated genes and 204 down-regulated genes, were identified from hemocytes after WSSV infection. Among these genes, 349 DEGs were correlated with innate immunity and categorized into seven groups based on their predictive function. Interestingly, 18 genes encoded putative neuropeptide precursors were induced significantly by WSSV infection. Furthermore, some genes were mapped to several typical processes in the NEI system, including proteolytic processing of prohormones, amino acid neurotransmitter pathways, biogenic amine biosynthesis and acetylcholine signaling pathway. Conclusions The data suggested that WSSV infection triggers the activation of NEI in shrimp, which throws a light on the pivotal roles of NEI system mediated by hemocytes in shrimp antiviral immunity. Electronic supplementary material The online version of this article (10.1186/s12864-019-5614-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Fuxuan Wang
- Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China.,Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China.,University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Shihao Li
- Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China.,Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China.,Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, 266071, China
| | - Jianhai Xiang
- Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China.,Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China
| | - Fuhua Li
- Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China. .,Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China. .,Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, 266071, China.
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27
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Inhibitory Effects of Prunella vulgaris L. Extract on 11 β-HSD1 in Human Skin Cells. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:1762478. [PMID: 30402116 PMCID: PMC6193348 DOI: 10.1155/2018/1762478] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Revised: 06/05/2018] [Accepted: 09/03/2018] [Indexed: 11/30/2022]
Abstract
Glucocorticoids are a risk factor for age-induced skin structure and function defects, and the glucocorticoid-activating enzyme, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), represents a promising therapeutic target. Prunella vulgaris L. (PV) is a perennial and an edible herbaceous plant normally cultivated in Asia and Europe. A recent study demonstrated a broad range of biological activities of PV including immune modulatory, antiviral, antiallergic, anti-inflammatory, antioxidant, and antidiabetic. However, little is known about the inhibitory effect of PV on 11β-HSD1. In this study, we investigated the inhibitory effect of Prunella vulgaris L. extract (PVE) and the underlying mechanism of 11β-HSD11 inhibition. Consistent with these results, cortisol levels were also reduced by PVE in vitro. The cortisone-induced translocation of glucocorticoids receptor (GR) was also attenuated. In addition, PVE inhibited a cortisone-mediated decrease in collagen content in skin. Collectively, these results suggest the beneficial effects of PVE in maintaining skin integrity.
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28
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Dhabhar FS. The short-term stress response - Mother nature's mechanism for enhancing protection and performance under conditions of threat, challenge, and opportunity. Front Neuroendocrinol 2018; 49:175-192. [PMID: 29596867 PMCID: PMC5964013 DOI: 10.1016/j.yfrne.2018.03.004] [Citation(s) in RCA: 147] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Revised: 03/23/2018] [Accepted: 03/23/2018] [Indexed: 02/07/2023]
Abstract
Our group has proposed that in contrast to chronic stress that can have harmful effects, the short-term (fight-or-flight) stress response (lasting for minutes to hours) is nature's fundamental survival mechanism that enhances protection and performance under conditions involving threat/challenge/opportunity. Short-term stress enhances innate/primary, adaptive/secondary, vaccine-induced, and anti-tumor immune responses, and post-surgical recovery. Mechanisms and mediators include stress hormones, dendritic cell, neutrophil, macrophage, and lymphocyte trafficking/function and local/systemic chemokine and cytokine production. Short-term stress may also enhance mental/cognitive and physical performance through effects on brain, musculo-skeletal, and cardiovascular function, reappraisal of threat/anxiety, and training-induced stress-optimization. Therefore, short-term stress psychology/physiology could be harnessed to enhance immuno-protection, as well as mental and physical performance. This review aims to provide a conceptual framework and targets for further investigation of mechanisms and conditions under which the protective/adaptive aspects of short-term stress/exercise can be optimized/harnessed, and for developing pharmacological/biobehavioral interventions to enhance health/healing, and mental/cognitive/physical performance.
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Affiliation(s)
- Firdaus S Dhabhar
- Department of Psychiatry & Behavioral Sciences, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Mail Stop M877, 1550 NW 10th Avenue, Miami, FL 33136-1000, United States.
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Tong J, Yu Y, Zheng L, Zhang C, Tu Y, Liu Y, Wu J, Li H, Wang S, Jiang C, Zhou EM, Wang G, Cai X. Hypothalamus-pituitary-adrenal axis involves in anti-viral ability through regulation of immune response in piglets infected by highly pathogenic porcine reproductive and respiratory syndrome virus. BMC Vet Res 2018. [PMID: 29540178 PMCID: PMC5853143 DOI: 10.1186/s12917-018-1414-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/07/2023] Open
Abstract
BACKGROUND The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) has been responsible for several viral attacks in the Asian porcine industry, since the first outbreak in China in 2006. During the early stages of the HP-PRRSV infection, high levels of proinflammatory cytokines are noted in the host peripheral blood, which are accompanied by severe lesions in the lungs and immune system organs; these are considered as the greatest contributors to the overall disease burden. We hypothesized that the anti-PRRSV response in piglets might be mediated by the hypothalamus-pituitary-adrenal (HPA) axis, which led to a decrease in the psycho-neuroendocrinological manifestation of HP-PRRSV etiology via immune response regulation. RESULTS We investigated the regulation of the HPA axis in HP-PRRSV-infected piglets that were treated with 1 mg/kg body weight (b. w.)/day mifepristone (RU486) or 2 mg/kg b.w./day dexamethasone (DEX). Both RU486 and DEX enhanced the disease status of the piglets infected by the HP-PRRSV HuN4 strain, resulting in high mortality and more severe pathological changes in the lungs. CONCLUSIONS HP-PRRSV infection activates the HPA axis, and artificial regulation of the immune-endocrine system enhances disease severity in HP-PRRSV-infected piglets. Thus, DEX and RU486 should be avoided in the clinical treatment of HP-PRRS.
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Affiliation(s)
- Jie Tong
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agriculture Science, Harbin, 150001, People's Republic of China
| | - Ying Yu
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agriculture Science, Harbin, 150001, People's Republic of China
| | - Linlin Zheng
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agriculture Science, Harbin, 150001, People's Republic of China
| | - Chong Zhang
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agriculture Science, Harbin, 150001, People's Republic of China
| | - Yabin Tu
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agriculture Science, Harbin, 150001, People's Republic of China
| | - Yonggang Liu
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agriculture Science, Harbin, 150001, People's Republic of China
| | - Jianan Wu
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agriculture Science, Harbin, 150001, People's Republic of China
| | - Hai Li
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agriculture Science, Harbin, 150001, People's Republic of China
| | - Shujie Wang
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agriculture Science, Harbin, 150001, People's Republic of China
| | - Chenggang Jiang
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agriculture Science, Harbin, 150001, People's Republic of China
| | - En-Min Zhou
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China
| | - Gang Wang
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agriculture Science, Harbin, 150001, People's Republic of China.
| | - Xuehui Cai
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agriculture Science, Harbin, 150001, People's Republic of China.
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Pan ZG, An XS. SARM1 deletion restrains NAFLD induced by high fat diet (HFD) through reducing inflammation, oxidative stress and lipid accumulation. Biochem Biophys Res Commun 2018; 498:416-423. [PMID: 29454967 DOI: 10.1016/j.bbrc.2018.02.115] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2018] [Accepted: 02/13/2018] [Indexed: 12/12/2022]
Abstract
SARM1 (Sterile alpha and armadillo motif-containing protein 1) is the recently identified TIR domain-containing cytosolic protein, which is involved in toll-like receptors (TLRs) signaling transduction. In the present study, the role of SARM1 in high fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) progression was explored. We found that SARM1 was expressed highly in fatty liver. And SARM1-knockout (KO) reduced steatohepatitis and metabolic disorders induced by HFD. SARM1-deletion decreased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in HFD-fed mice. Additionally, inflammatory response caused by HFD was alleviated by SARM1-deletion through inactivating TLR4/7/9 and nuclear factor kappa B (NF-κB) pathways. Of note, SARM1-deletion also reduced the expressions of inflammation-associated molecules in hypothalamus of HFD-fed mice. Furthermore, HFD administration led to oxidative stress in liver of mice, while being decreased in SARM1-KO mice. Moreover, SARM1-ablation improved lipid dyslipidemia by suppressing the mRNA levels of genes, linked to glycolysis, lipogenesis and transcriptional regulation. Insulin resistance was also attenuated by SARM1-deficiency through enhancing the activation of liver Akt/glycogen synthase kinase-3β (GSK3β) and insulin receptor substrate-1 (IRS1)/FOXO1 pathways in HFD-fed mice. Also, SARM1-knockout improved neuropeptide Y (NPY), Pro-Opiomelanocortins (POMC), Agouti-related Protein (AGRP) and Cocaine-and-Amphetamine Responsive Transcript 1 (CART1) expressions in hypothalamus of mice after HFD administration. In vitro, we found that the reduction of inflammatory response, oxidative stress and dyslipidemia induced by SARM1-knockout in primary hepatocytes after fructose stimulation was largely attributed to its suppression to TLR4/7/9. Together, the findings demonstrated that SARM1 might be an effective target for developing effective therapeutic strategies against NAFLD.
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Affiliation(s)
- Zhen-Guo Pan
- Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300, PR China
| | - Xu-Sheng An
- Intensive Care Unit, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300, PR China.
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31
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Rocha de Sousa PT, Breithaupt-Faloppa AC, de Jesus Correia C, Simão RR, Ferreira SG, Fiorelli AI, Moreira LFP, Sannomiya P. 17β-Estradiol prevents mesenteric injury induced by occlusion of the proximal descending aorta in male rats. J Vasc Surg 2018; 67:597-606. [DOI: 10.1016/j.jvs.2016.12.125] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Accepted: 12/17/2016] [Indexed: 02/07/2023]
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32
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Petramala L, Olmati F, Conforti MG, Concistré A, Bisogni V, Alfieri N, Iannucci G, de Toma G, Letizia C. Autoimmune Diseases in Patients with Cushing's Syndrome after Resolution of Hypercortisolism: Case Reports and Literature Review. Int J Endocrinol 2018; 2018:1464967. [PMID: 30662460 PMCID: PMC6312625 DOI: 10.1155/2018/1464967] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Accepted: 11/13/2018] [Indexed: 12/28/2022] Open
Abstract
INTRODUCTION Cushing's syndrome (CS) is a clinical condition characterized by excessive cortisol production, associated with metabolic complications, such as diabetes mellitus, dyslipidemia, metabolic syndrome, hypertension, and cardiovascular diseases. Nowadays, the occurrence of autoimmune diseases in CS have not been completely evaluated in the previous studies. OBJECTIVE The aim of this study was to evaluate the occurrence of autoimmune diseases in CS patients after successfully treated. MATERIALS AND METHODS From January 2001 to December 2017, in our Secondary Hypertension Unit, we evaluated 147 CS patients (91 with ACTH-independent disease, 54 with ACTH-dependent disease, and 2 patients with ectopic ACTH production. RESULTS 109 CS patients (74.1%) were surgically treated (67 ACTH-independent CS patients (61.5%) undergone adrenalectomy and 42 ACTH-dependent CS (38.5%) undergone transsphenoidal surgery) and evaluated after 6, 12, and 24 months after clinical and biochemical remission of disease. In 9 (8.3%) of overall treated CS patients (8.3%), during follow-up, we observed the onset of some manifestations of autoimmune diseases. In particular, one patient had a systemic lupus erythematosus, one patient had rheumatoid arthritis, 4 patients reported autoimmune thyroiditis (Basedow-Graves' disease and Hashimoto's thyroiditis), one patient had clinical features of psoriasis, one patient showed myasthenia gravis, and one patient had giant cell arteritis. CONCLUSIONS Our results demonstrate that patients successfully treated for CS could develop autoimmune diseases. Therefore, after treatment, CS patients need to be strictly monitored in order to evaluate the possible onset of autoimmune diseases.
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Affiliation(s)
- Luigi Petramala
- Secondary Hypertension Unit, Department of Transactional Medicine and Precision, University of Rome “La Sapienza”, Rome, Italy
| | - Federica Olmati
- Secondary Hypertension Unit, Department of Transactional Medicine and Precision, University of Rome “La Sapienza”, Rome, Italy
| | - Maria Gabriella Conforti
- Secondary Hypertension Unit, Department of Transactional Medicine and Precision, University of Rome “La Sapienza”, Rome, Italy
| | - Antonio Concistré
- Secondary Hypertension Unit, Department of Transactional Medicine and Precision, University of Rome “La Sapienza”, Rome, Italy
| | - Valeria Bisogni
- Secondary Hypertension Unit, Department of Transactional Medicine and Precision, University of Rome “La Sapienza”, Rome, Italy
| | - Nikita Alfieri
- Secondary Hypertension Unit, Department of Transactional Medicine and Precision, University of Rome “La Sapienza”, Rome, Italy
| | - Gino Iannucci
- Secondary Hypertension Unit, Department of Transactional Medicine and Precision, University of Rome “La Sapienza”, Rome, Italy
| | - Giorgio de Toma
- Department of Surgery “P. Valdoni”, University of Rome “La Sapienza”, Rome, Italy
| | - Claudio Letizia
- Secondary Hypertension Unit, Department of Transactional Medicine and Precision, University of Rome “La Sapienza”, Rome, Italy
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Aldaba-Muruato LR, Muñoz-Ortega MH, Macías-Pérez JR, Pulido-Ortega J, Martínez-Hernández SL, Ventura-Juárez J. Adrenergic regulation during acute hepatic infection with Entamoeba histolytica in the hamster: involvement of oxidative stress, Nrf2 and NF-KappaB. Parasite 2017; 24:46. [PMID: 29185982 PMCID: PMC5706999 DOI: 10.1051/parasite/2017048] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Accepted: 11/06/2017] [Indexed: 12/19/2022] Open
Abstract
Oxidative stress and transcriptional pathways of nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa-B (NF-κB) are critically involved in the etiopathology of amebic liver abscess (ALA). In this work, we studied the relationship between the adrenergic nervous system and ALA in the hamster. ALA was visible at 12 h of infection. While 6-hydroxidopamine (6-OHDA) decreased infection, propranolol (β-adrenergic blocker) treatment was associated with less extensive liver damage, and phentolamine treatment (α-adrenergic blocker) significantly reduced ALA compared to 6-OHDA and propranolol. Serum enzymatic activities of alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (γ-GTP) were increased at 12 h post-infection. Chemical denervation and α and β-adrenergic blockers decreased ALT to normal levels, while 6-OHDA and propranolol showed a trend to decrease γ-GTP but phentolamine significantly reduced γ-GTP. Amebic infection increased oxidized glutathione (GSSG) and decreased both reduced glutathione (GSH) and the GSH/GSSG ratio. Propranolol and 6-OHDA showed a tendency to decrease GSSG. However, GSH, GSSG and GSH/GSSG returned to normal levels with phentolamine. Furthermore, amebic infection increased pNF-κB and interleukin-1β (IL-1β), and showed a tendency to decrease hemoxigenase-1 (HO-1), but not Nrf2. Chemical denervation showed a trend to decrease pNF-κB and IL-1β, and neither Nrf2 nor HO-1 increased significantly. In addition, NF-κB and IL-1β were attenuated by propranolol and phentolamine treatments, although phentolamine showed significant overexpression of Nrf2 and HO-1. This suggests that the adrenergic system may be involved in oxidative stress and in modulation of the Nrf2 and NF-κB pathways during ALA development.
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Affiliation(s)
| | - Martín Humberto Muñoz-Ortega
- Departamento de Química, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes,
Aguascalientes,
Ags. México
| | - José Roberto Macías-Pérez
- Química Clínica, Unidad Académica Multidisciplinaria Zona Huasteca, Universidad Autónoma de San Luis Potosí,
Ciudad Valles,
SLP. México
| | - Julieta Pulido-Ortega
- Departamento de Morfología, Universidad Autónoma de Aguascalientes,
Aguascalientes,
Ags. México
| | | | - Javier Ventura-Juárez
- Departamento de Morfología, Universidad Autónoma de Aguascalientes,
Aguascalientes,
Ags. México
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Lin TK, Zhong L, Santiago JL. Association between Stress and the HPA Axis in the Atopic Dermatitis. Int J Mol Sci 2017; 18:ijms18102131. [PMID: 29023418 PMCID: PMC5666813 DOI: 10.3390/ijms18102131] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 10/06/2017] [Accepted: 10/09/2017] [Indexed: 02/07/2023] Open
Abstract
The hypothalamic–pituitary–adrenal (HPA) axis is one of the body’s neuroendocrine networks that responds to psychological stress (PS). In the skin, there exists a peripheral HPA axis similar to the central axis. Glucocorticoids (GCs) are key effector molecules of the HPA axis and are essential for cutaneous homeostasis. Atopic dermatitis (AD) is a condition typically characterized by a chronic relapsing course that often results in PS. HPA dysfunction is present in AD patients by the decreased response of GCs elevation to stress as compared to those unaffected by AD. Nevertheless, in skin, acute PS activates several metabolic responses that are of immediate benefit to the host. During the acute phase of PS, increased endogenous GCs have been shown to provide benefit rather than by aggravating cutaneous inflammatory dermatoses. However, a chronic T helper cell type 2 (Th2) predominant cytokine profile acts as a negative feedback loop to blunt the HPA axis response in AD. In this article, we reviewed the role of CRF, pro-opiomelanocortin (POMC)-derived peptides, GCs of the HPA, and 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in AD, with a discussion of the pathogenetic mechanisms of inflammation and skin barrier functions, including antimicrobial defense, and their association with PS.
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Affiliation(s)
- Tzu-Kai Lin
- Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
| | - Lily Zhong
- Citrus Valley Medical Center, West Covina, CA 91790, USA.
| | - Juan Luis Santiago
- Dermatology Service & Translational Research Unit (UIT), Hospital General Universitario de Ciudad Real, Ciudad Real 13005, Spain.
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Stress Induced Polarization of Immune-Neuroendocrine Phenotypes in Gallus gallus. Sci Rep 2017; 7:8102. [PMID: 28808318 PMCID: PMC5556001 DOI: 10.1038/s41598-017-08733-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Accepted: 07/14/2017] [Indexed: 12/11/2022] Open
Abstract
Immune-neuroendocrine phenotypes (INPs) stand for population subgroups differing in immune-neuroendocrine interactions. While mammalian INPs have been characterized thoroughly in rats and humans, avian INPs were only recently described in Coturnix coturnix (quail). To assess the scope of this biological phenomenon, herein we characterized INPs in Gallus gallus (a domestic hen strain submitted to a very long history of strong selective breeding pressure) and evaluated whether a social chronic stress challenge modulates the individuals' interplay affecting the INP subsets and distribution. Evaluating plasmatic basal corticosterone, interferon-γ and interleukin-4 concentrations, innate/acquired leukocyte ratio, PHA-P skin-swelling and induced antibody responses, two opposite INP profiles were found: LEWIS-like (15% of the population) and FISCHER-like (16%) hens. After chronic stress, an increment of about 12% in each polarized INP frequency was found at expenses of a reduction in the number of birds with intermediate responses. Results show that polarized INPs are also a phenomenon occurring in hens. The observed inter-individual variation suggest that, even after a considerable selection process, the population is still well prepared to deal with a variety of immune-neuroendocrine challenges. Stress promoted disruptive effects, leading to a more balanced INPs distribution, which represents a new substrate for challenging situations.
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Csaba G. The Role of Brain –Pineal –Thymus System in the Determination of Lifespan: The Autoimmune Aging Theory. ACTA ACUST UNITED AC 2017. [DOI: 10.3233/nib-160118] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- G. Csaba
- Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary
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Ziebell JM, Rowe RK, Muccigrosso MM, Reddaway JT, Adelson PD, Godbout JP, Lifshitz J. Aging with a traumatic brain injury: Could behavioral morbidities and endocrine symptoms be influenced by microglial priming? Brain Behav Immun 2017; 59:1-7. [PMID: 26975888 DOI: 10.1016/j.bbi.2016.03.008] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2015] [Revised: 03/01/2016] [Accepted: 03/11/2016] [Indexed: 12/20/2022] Open
Abstract
A myriad of factors influence the developmental and aging process and impact health and life span. Mounting evidence indicates that brain injury, even moderate injury, can lead to lifetime of physical and mental health symptoms. Therefore, the purpose of this mini-review is to discuss how recovery from traumatic brain injury (TBI) depends on age-at-injury and how aging with a TBI affects long-term recovery. TBI initiates pathophysiological processes that dismantle circuits in the brain. In response, reparative and restorative processes reorganize circuits to overcome the injury-induced damage. The extent of circuit dismantling and subsequent reorganization depends as much on the initial injury parameters as other contributing factors, such as genetics and age. Age-at-injury influences the way the brain is able to repair itself, as a result of developmental status, extent of cellular senescence, and injury-induced inflammation. Moreover, endocrine dysfunction can occur with TBI. Depending on the age of the individual at the time of injury, endocrine dysfunction may disrupt growth, puberty, influence social behaviors, and possibly alter the inflammatory response. In turn, activation of microglia, the brain's immune cells, after injury may continue to fuel endocrine dysfunction. With age, the immune system develops and microglia become primed to subsequent challenges. Sustained inflammation and microglial activation can continue for weeks to months post-injury. This prolonged inflammation can influence developmental processes, behavioral performance and age-related decline. Overall, brain injury may influence the aging process and expedite glial and neuronal alterations that impact mental health.
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Affiliation(s)
- Jenna M Ziebell
- Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, Tasmania, Australia; Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA; Department of Child Health, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA.
| | - Rachel K Rowe
- Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA; Department of Child Health, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA; Neuroscience Graduate Program, Arizona State University, Tempe, AZ, USA
| | | | - Jack T Reddaway
- Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA; Department of Child Health, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA; University of Bath, Department of Biology and Biochemistry, Bath, United Kingdom
| | - P David Adelson
- Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA; Department of Child Health, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA; University of Bath, Department of Biology and Biochemistry, Bath, United Kingdom
| | - Jonathan P Godbout
- Department of Neuroscience, Ohio State University, Columbus, OH, USA; Center for Brain and Spinal Cord Repair, Ohio State University, Columbus, OH, USA; Institute for Behavioral Medicine Research, Ohio State University, Columbus, OH, USA
| | - Jonathan Lifshitz
- Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA; Department of Child Health, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA; Neuroscience Graduate Program, Arizona State University, Tempe, AZ, USA; VA Healthcare System, Phoenix, AZ, USA
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Arick CT. Chiropractic Management of a Patient With Chronic Fatigue: A Case Report. J Chiropr Med 2016; 15:314-320. [PMID: 27857641 PMCID: PMC5106444 DOI: 10.1016/j.jcm.2016.08.006] [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: 01/06/2016] [Revised: 08/05/2016] [Accepted: 08/05/2016] [Indexed: 11/23/2022] Open
Abstract
OBJECTIVE The purpose of this case report was to describe the examination and management of a patient with chronic fatigue. CLINICAL FEATURES A 34-year-old woman presented to a chiropractic clinic with complaints of fatigue and inability to lose weight for 2 years. When tested, she was found to have high serum thyroglobulin antibodies, low serum vitamin D3, low saliva dehydroepiandrosterone-sulfate, and low saliva total and diurnal cortisol. INTERVENTION AND OUTCOME The patient was placed on an anti-inflammatory ancestral diet and given recommendations to decrease the aerobic intensity of her exercise routine. On the basis of the result of conventional and functional laboratory tests, she was prescribed a treatment plan of targeted supplementation. After 12 weeks of application of dietary, lifestyle, and supplementation recommendations, the patient reported experiencing increased energy and weight loss of 15 pounds. Her thyroglobulin antibodies returned within reference range, salivary cortisol increased and closely followed the proper circadian rhythm, and dehydroepiandrosterone-sulfate increased. CONCLUSIONS This report describes improvement in a patient with chronic fatigue with the use of nonpharmaceutical polytherapy involving dietary changes, lifestyle modification, and supplementation.
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Affiliation(s)
- Christopher T. Arick
- Clinical Sciences Department, National University of Health Sciences, Pinellas Park, FL
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de Oliveira CC, Gouveia FV, de Castro MC, Kuroki MA, Dos Santos LCT, Fonoff ET, Teixeira MJ, Otoch JP, Martinez RCR. A Window on the Study of Aversive Instrumental Learning: Strains, Performance, Neuroendocrine, and Immunologic Systems. Front Behav Neurosci 2016; 10:162. [PMID: 27605910 PMCID: PMC4995215 DOI: 10.3389/fnbeh.2016.00162] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2016] [Accepted: 08/08/2016] [Indexed: 12/20/2022] Open
Abstract
The avoidance response is present in pathological anxiety and interferes with normal daily functions. The aim of this article is to shed light on performance markers of active avoidance (AA) using two different rat strains, Sprague-Dawley (SD) and Wistar. Specifically, good and poor performers were evaluated regarding anxiety traits exhibited in the elevated plus maze (EPM) and corticosterone levels and motor activity in the open field test. In addition, the plasma levels of Interleukin-6 (IL-6), Interleukin-1Beta (IL-1beta), Nerve Growth Factor Beta (NGF-beta), Tumor Necrosis Factor-Alpha (TNF-alpha) and cytokine-induced neutrophil chemoattractant 1 (CINC-1) were compared in the good and poor performers to better understand the role of the immunologic system in aversive learning. Behavioral criteria were employed to identify subpopulations of SD and Wistar rats based on their behavioral scores during a two-way AA test. The animals were tested for anxiety-like behavior in the EPM and motor activity in the open-field test. Plasma corticosterone levels were measured at the end of the avoidance test. Cytokine levels of IL-6, IL-1beta, NGF-beta, TNF-alpha, and CINC-1 were measured in the plasma of the Wistar rats. Sixty-six percent of the Wistar rats and 35% of the SD rats exhibited a poor performance. This feature was associated with a decrease in anxiety-like behavior in the EPM. The poor and good performers exhibited lower levels of corticosterone compared with the control animals, which suggests that training alters corticosterone levels, thereby leading to hypocortisolism, independent of the performance. The CINC-1 levels were increased in the poor performers, which reinforces the role of immunologic system activation in learning deficits. Our study provides a better understanding of the complex interactions that underlie neuroimmune consequences and their implications for performance.
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Affiliation(s)
- Caroline C de Oliveira
- Laboratory of Neuromodulation and Experimental Pain, Hospital Sirio-Libanes Sao Paulo, Brazil
| | - Flávia V Gouveia
- Laboratory of Neuromodulation and Experimental Pain, Hospital Sirio-Libanes Sao Paulo, Brazil
| | - Marina C de Castro
- Laboratory of Neuromodulation and Experimental Pain, Hospital Sirio-Libanes Sao Paulo, Brazil
| | - Mayra A Kuroki
- Laboratory of Neuromodulation and Experimental Pain, Hospital Sirio-Libanes Sao Paulo, Brazil
| | - Lennon C T Dos Santos
- Laboratory of Neuromodulation and Experimental Pain, Hospital Sirio-Libanes Sao Paulo, Brazil
| | - Erich T Fonoff
- Division of Functional Neurosurgery, Department of Neurology, School of Medicine, Institute of Psychiatry, University of Sao Paulo Sao Paulo, Brazil
| | - Manoel J Teixeira
- Division of Functional Neurosurgery, Department of Neurology, School of Medicine, Institute of Psychiatry, University of Sao Paulo Sao Paulo, Brazil
| | - José P Otoch
- Department of Surgery Techniques, School of Medicine, University of Sao Paulo Sao Paulo, Brazil
| | - Raquel C R Martinez
- Division of Functional Neurosurgery, Department of Neurology, School of Medicine, Institute of Psychiatry, University of Sao Paulo Sao Paulo, Brazil
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Mravec B. Letter To the Editor: Autonomic dysfunction in autoimmune diseases: consequence or cause? Lupus 2016; 16:767-8. [PMID: 17728374 DOI: 10.1177/0961203307081843] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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Sung N, Salazar García MD, Dambaeva S, Beaman KD, Gilman-Sachs A, Kwak-Kim J. Gonadotropin-releasing hormone analogues lead to pro-inflammatory changes in T lymphocytes. Am J Reprod Immunol 2016; 76:50-8. [DOI: 10.1111/aji.12522] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Accepted: 04/27/2016] [Indexed: 12/25/2022] Open
Affiliation(s)
- Nayoung Sung
- Reproductive Medicine; Department of Obstetrics and Gynecology; Chicago Medical School at Rosalind Franklin University of Medicine and Science; Vernon Hills IL USA
| | - María D. Salazar García
- Reproductive Medicine; Department of Obstetrics and Gynecology; Chicago Medical School at Rosalind Franklin University of Medicine and Science; Vernon Hills IL USA
| | - Svetlana Dambaeva
- Department of Microbiology and Immunology; Chicago Medical School at Rosalind Franklin University of Medicine and Science; North Chicago IL USA
| | - Kenneth D. Beaman
- Department of Microbiology and Immunology; Chicago Medical School at Rosalind Franklin University of Medicine and Science; North Chicago IL USA
| | - Alice Gilman-Sachs
- Department of Microbiology and Immunology; Chicago Medical School at Rosalind Franklin University of Medicine and Science; North Chicago IL USA
| | - Joanne Kwak-Kim
- Reproductive Medicine; Department of Obstetrics and Gynecology; Chicago Medical School at Rosalind Franklin University of Medicine and Science; Vernon Hills IL USA
- Department of Microbiology and Immunology; Chicago Medical School at Rosalind Franklin University of Medicine and Science; North Chicago IL USA
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Feitosa CA, Santos DN, Barreto ML, Rodrigues LC. The effect of internalization and other psychologic factors on the remission and severity of wheeze in children. Pediatr Allergy Immunol 2016; 27:398-403. [PMID: 26843104 DOI: 10.1111/pai.12545] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/01/2016] [Indexed: 11/28/2022]
Abstract
BACKGROUND Asthma prevalence in Latin America is high and continues to increase. There is evidence that the psychologic characteristics of the child are associated with greater asthma morbidity. This study aimed to investigate the independent effect of internalizing/externalizing problems on two asthma/wheeze outcomes: (i) remission and (ii) progression to severity on Latin American children with mild asthma symptoms at baseline. METHODS This was a prospective study in a cohort of 371 asthmatic children living in a poor urban area in Salvador, Brazil. The psychologic characteristics of the child were assessed using the Child Behavior Checklist (CBCL), and wheezing was defined using the ISAAC questionnaire at the start and end of follow-up. A multiple logistic regression model with random effects was used to examine the association between the psychologic components and both outcomes. RESULTS Remission of symptoms of wheeze was observed among 229 (61.73%) children. Remission was 56% lower among children with internalizing problems (OR = 0.54, 95% CI 0.33-0.87, p = 0.01). In addition, we found that 19 (8.76%) of the children acquired severe symptoms during follow-up and there was strong evidence of the effect of internalizing problems in increasing the risk of progression to severe wheeze symptoms (OR = 4.03, 95% CI 1.39-11.70, p = 0.01). CONCLUSIONS Children with internalizing problems but not externalizing had less remission of wheezing, and a higher risk of acquiring severe symptoms. These results highlight the importance of psychologic care for children with asthma, to improve the prognosis of this condition.
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Affiliation(s)
- Caroline A Feitosa
- Institute of Collective Health, Federal University of Bahia - ISC/UFBA, Salvador, Brazil
| | - Darci N Santos
- Institute of Collective Health, Federal University of Bahia - ISC/UFBA, Salvador, Brazil
| | - Maurício L Barreto
- Institute of Collective Health, Federal University of Bahia - ISC/UFBA, Salvador, Brazil
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The simple neuroendocrine-immune regulatory network in oyster Crassostrea gigas mediates complex functions. Sci Rep 2016; 6:26396. [PMID: 27193598 PMCID: PMC4872224 DOI: 10.1038/srep26396] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2015] [Accepted: 04/29/2016] [Indexed: 01/01/2023] Open
Abstract
The neuroendocrine-immune (NEI) regulatory network is a complex system, which plays an indispensable role in the immunity of the host. In the present study, the bioinformatical analysis of the transcriptomic data from oyster Crassostrea gigas and further biological validation revealed that oyster TNF (CgTNF-1 CGI_10018786) could activate the transcription factors NF-κB and HSF (heat shock transcription factor) through MAPK signaling pathway, and then regulate apoptosis, redox reaction, neuro-regulation and protein folding in oyster haemocytes. The activated immune cells then released neurotransmitters including acetylcholine, norepinephrine and [Met(5)]-enkephalin to regulate the immune response by arising the expression of three TNF (CGI_10005109, CGI_10005110 and CGI_10006440) and translocating two NF-κB (Cgp65, CGI_10018142 and CgRel, CGI_10021567) between the cytoplasm and nuclei of haemocytes. Neurotransmitters exhibited the immunomodulation effects by influencing apoptosis and phagocytosis of oyster haemocytes. Acetylcholine and norepinephrine could down-regulate the immune response, while [Met(5)]-enkephalin up-regulate the immune response. These results suggested that the simple neuroendocrine-immune regulatory network in oyster might be activated by oyster TNF and then regulate the immune response by virtue of neurotransmitters, cytokines and transcription factors.
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Agha-Hosseini F, Shirzad N, Moosavi MS. The association of elevated plasma cortisol and Hashimoto's Thyroiditis, a neglected part of immune response. Acta Clin Belg 2016; 71:81-5. [PMID: 27075805 DOI: 10.1080/17843286.2015.1116152] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
INTRODUCTION Currently, Hashimoto Thyroiditis (HT) is the most common autoimmune disease and its prevalence is reported to be about twice that of Type 1 diabetes. Any disturbances in the immune tolerance system may cause autoimmune diseases. Discovering the underlying immune disturbances in HT not only improves our knowledge of its aetiopathology, but may also provide opportunities for appropriate management and preventing further immunological biases. PATIENTS AND METHODS Forty women diagnosed with HT were enrolled in this study. After the subjects had sat quietly for 30-40 min, blood samples were taken between 08:00 and 09:00 am. Cortisol, autoantibodies and TSH were measured by ELISA test. RESULTS There were no significant differences in terms of age, BMI or number of menopause women between HT patients and normal group. Cortisol was significantly higher in the HT group. The adjusted odds ratio for increased probability of HT for 1 ng increase in cortisol value was 19%. DISCUSSION After matching age and menopause status, cortisol was higher in the HT group. The Th2 immune response due to cortisol may have a protective role in certain types of autoimmunity. The presence of immunoreactive corticotropin-releasing hormone in thyroid lesions, predominantly in those related to autoimmune disorders may support hyperproduction of cortisol in HT. CONCLUSION Glucocorticoids downregulate the immune system and are known as one of the major immunosuppressant factors. In this study, there was increased cortisol level in HT patients.
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Porcelli B, Pozza A, Bizzaro N, Fagiolini A, Costantini MC, Terzuoli L, Ferretti F. Association between stressful life events and autoimmune diseases: A systematic review and meta-analysis of retrospective case–control studies. Autoimmun Rev 2016; 15:325-34. [DOI: 10.1016/j.autrev.2015.12.005] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2015] [Accepted: 12/15/2015] [Indexed: 01/06/2023]
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Attenuated allergic inflammatory response in the lungs during lactation. Life Sci 2016; 151:281-287. [PMID: 26979776 DOI: 10.1016/j.lfs.2016.03.027] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Revised: 03/08/2016] [Accepted: 03/11/2016] [Indexed: 12/31/2022]
Abstract
AIMS To evaluate the influence of lactation on lung immune function during allergic inflammation. MAIN METHODS Female rats, 60-90days old, were divided into three groups: no lung allergy virgins (N group), ovalbumin (OVA)-immunized and sensitized virgins (V group), and OVA-immunized and sensitized lactating females (L group). On gestation day (GD) 10, all animals in L group received a subcutaneous injection of 0.1mg·kg(-1) OVA plus aluminum hydroxide. On GD17, the L group received a subcutaneous booster injection of 10μg OVA plus 10mg aluminum hydroxide. After 7days, an inhalatory challenge with 1% OVA was given in 15min sessions for 3 consecutive days. Animals from the V group received the same treatment, meaning both tests and time intervals between OVA treatment and inhalatory challenge were the same as in the L group. Twenty-four hours after the last inhalation session, the animals were euthanized, and the following tests were performed: total and differential bronchoalveolar lavage (BAL) and femoral marrow lavage (FML) leukocyte counts, quantification of tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ) levels in BAL fluid, and quantification of plasma corticosterone and catecholamine levels. KEY FINDINGS The L group presented lower BAL total leukocyte counts and decreases in the number of eosinophils and macrophages compared with the V group. They also expressed higher BAL IFN-γ and lower plasma corticosterone levels. Plasma norepinephrine levels were higher in the L group than in the N and V groups. SIGNIFICANCE Lactating female rats presented less intense allergic lung inflammation. Our findings suggest that lactation may protect females from asthmatic crises.
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Sahoo JP, Selviambigapathy J, Kamalanathan S, Nagarajan K, Vivekanandan M. Effect of steroid replacement on thyroid function and thyroid autoimmunity in Addison's disease with primary hypothyroidism. Indian J Endocrinol Metab 2016; 20:162-166. [PMID: 27042409 PMCID: PMC4792014 DOI: 10.4103/2230-8210.176356] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Steroid replacement without thyroxine supplementation normalizes thyroid function test (TFT) in some but not all Addison's disease patients with primary hypothyroidism. Both autoimmune and nonautoimmune mechanisms contribute to this improvement in TFT. However, the documentation of the change in thyroid autoimmunity after cortisol replacement is very limited in the literature. The aim of this study was to determine the effect of steroid replacement on TFT and anti-thyroid peroxidase antibody (anti-TPO-Ab) titer in Addison's disease with primary hypothyroidism. MATERIALS AND METHODS This observational study was conducted in a tertiary care center in South India. Six Addison's disease patients with primary hypothyroidism, who were only on steroid replacement, were included in the study. Low serum cortisol (<83 nmol/L) with high plasma adrenocorticotropic hormone (>22 pmol/L) and/or hyperpigmentation of skin/mucous membranes was considered as the diagnostic criteria for Addison's disease. Primary hypothyroidism (both overt and subclinical) was defined as high thyroid stimulating hormone (TSH) with/without low free thyroxine (fT4). TFT and anti-TPO-Ab were performed before and after steroid replacement in all of them. RESULTS Poststeroid replacement, there was a normalization of TSH in all but one subjects. In overt hypothyroidism patients, fT4 also normalized. The improvement in TFT was not associated with decreasing titer of the anti-TPO-Ab in all six patients. However, there was a significant difference in TSH after steroid replacement compared to the baseline status. CONCLUSIONS The concept of normalization of primary hypothyroidism with cortisol replacement in patients with Addison's disease should be recognized to avoid iatrogenic thyrotoxicosis caused by thyroxine replacement. Both autoimmune and nonautoimmune mechanisms contribute to these alterations.
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Affiliation(s)
- Jaya Prakash Sahoo
- Department of Endocrinology and Metabolism, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Jayakumar Selviambigapathy
- Department of Endocrinology and Metabolism, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Sadishkumar Kamalanathan
- Department of Endocrinology and Metabolism, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - K. Nagarajan
- Department of Radiodiagnosis, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Muthupillai Vivekanandan
- Department of Endocrinology and Metabolism, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
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Pastore F, Martocchia A, Stefanelli M, Prunas P, Giordano S, Toussan L, Devito A, Falaschi P. Hepatitis C virus infection and thyroid autoimmune disorders: A model of interactions between the host and the environment. World J Hepatol 2016; 8:83-91. [PMID: 26807204 PMCID: PMC4716530 DOI: 10.4254/wjh.v8.i2.83] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 10/28/2015] [Accepted: 12/04/2015] [Indexed: 02/06/2023] Open
Abstract
The hepatitis C virus (HCV) infection is an important public health problem and it is associated with hepatic and extrahepatic manifestations. Autoimmune thyroid diseases are common in HCV infected patients and the standard interferon-based treatment is associated with an increase of the immune-mediated thyroid damage. Recent evidence in the literature analyzed critical points of the mechanisms of thyroid damage, focusing on the balance between the two sides of the interaction: The environment (virus infection with potential cross-reaction) and the host (susceptibility genes with consistent immune response). The spectrum of antiviral treatment for chronic HCV infection is rapidly expanding for the development of dual o triple therapy. The availability of interferon-free combined treatment with direct antiviral agents for HCV is very promising, in order to ameliorate the patient compliance and to reduce the development of thyroid autoimmunity.
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Xiang L, Sunesara I, Rehm KE, Marshall Jr GD. A modified and cost-effective method for hair cortisol analysis. Biomarkers 2016; 21:200-3. [DOI: 10.3109/1354750x.2015.1130748] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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A New Direction: Neuro-endocrino-immunology. Neuroophthalmology 2016. [DOI: 10.1007/978-3-319-28956-4_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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