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Alshelh Z, Brusaferri L, Morrissey EJ, Torrado-Carvajal A, Kim M, Akeju O, Grmek G, Chane C, Murphy J, Schrepf A, Harris RE, Kwon YM, Bedair H, Siliski J, Chen AF, Melnic C, Jarraya M, Napadow V, Veronese M, Maccioni L, Edwards RR, Efthimiou N, Mohammadian M, Luo E, Pollak LE, Catana C, Toschi N, Loggia ML. Brain inflammation and its predictive value for post-operative pain in total knee arthroplasty patients. Brain Behav Immun 2025; 128:703-712. [PMID: 40354834 DOI: 10.1016/j.bbi.2025.05.008] [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: 12/09/2024] [Revised: 04/15/2025] [Accepted: 05/07/2025] [Indexed: 05/14/2025] Open
Abstract
Recent evidence suggests that chronic pain patients exhibit elevated brain levels of the neuroinflammation marker 18 kDa translocator protein (TSPO). However, the clinical significance of brain TSPO elevations, and their responses to pain interventions, remain unknown. To explore these questions, we studied patients with knee osteoarthritis (KOA) undergoing total knee arthroplasty (TKA), a procedure which is curative for most, but carries a relatively high risk of persistent post-surgical pain. Pre-surgical KOA patients (n = 41) and healthy controls (n = 22) underwent brain positron emission tomography/magnetic resonance imaging, using the TSPO radioligand [11C]PBR28. A subset of KOA patients (n = 27) returned for a second scan one-year post-TKA. When compared groups, pre-surgical KOA patients exhibited widespread [11C]PBR28 PET signal elevations (Standardized Uptake Value Ratio), with pituitary uptake positively correlating with knee pain severity (rho = 0.51; p = 0.003). A voxel-wise paired t-test revealed that while most brain regions showed no change post-surgery, the [11C]PBR28 PET signal significantly decreased in the thalamus and caudate, reaching control levels. Additionally, a Support Vector Machine model based on pre-surgical imaging, clinical, and demographic features, achieved a correlation of rho = 0.487 (p = 0.001) between the predicted and actual pain improvement. Top predictive features included [11C]PBR28 uptake in the pituitary gland, cuneal cortex, amygdala and other regions. This study suggests that neuroinflammation 1) is widespread in KOA and, in some regions, 2) is linked to pain severity, 3) undergoes normalization following TKA, and 4) can predict post-surgical TKA outcomes. Understanding the neuroinflammatory mechanisms in KOA and post-surgical pain may guide targeted interventions and improve patient outcomes.
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Affiliation(s)
- Zeynab Alshelh
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States; Brain and Mind Centre, University of Sydney, Sydney, Australia
| | - Ludovica Brusaferri
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States; Department of Computer Science and Digital Technology, College of Technology and Environment, London South Bank University, London, UK
| | - Erin Janas Morrissey
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States
| | - Angel Torrado-Carvajal
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States; Medical Image Analysis and Biometry Laboratory, Universidad Rey Juan Carlos, Madrid, Spain
| | - Minhae Kim
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States
| | - Oluwaseun Akeju
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Grace Grmek
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States
| | - Courtney Chane
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States
| | - Jennifer Murphy
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States
| | - Andrew Schrepf
- Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan, Ann Arbor, MI, United States
| | - Richard E Harris
- Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan, Ann Arbor, MI, United States; Susan Samueli Integrative Health Institute, School of Medicine, University of California at Irvine, Irvine CA, United States; Department of Anesthesiology and Perioperative Care, School of Medicine, University of California at Irvine, Irvine CA, United States
| | - Young-Min Kwon
- Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Hany Bedair
- Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - John Siliski
- Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Antonia F Chen
- Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
| | - Christopher Melnic
- Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Mohamed Jarraya
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States
| | - Vitaly Napadow
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States; Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Charlestown, MA, United States
| | - Mattia Veronese
- Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Department of Information Engineering, University of Padua, Italy
| | - Lucia Maccioni
- Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
| | - Robert R Edwards
- Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
| | - Nikos Efthimiou
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States
| | - Mehrbod Mohammadian
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States
| | - Ekim Luo
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States
| | - Lauren E Pollak
- Department of Psychiatry, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States
| | - Ciprian Catana
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States
| | - Nicola Toschi
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States; Department of Biomedicine and Prevention, University of Rome, "Tor Vergata", Rome, Italy
| | - Marco L Loggia
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
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Chen H, Chen Y, Chen X, Tang L, Liu J, Shi WJ, Ou YH. Exploring the link between serum uric acid and endometriosis: a cross-sectional analysis utilizing NHANES data from 1999-2006. Front Endocrinol (Lausanne) 2025; 16:1536300. [PMID: 40303639 PMCID: PMC12037370 DOI: 10.3389/fendo.2025.1536300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Accepted: 03/26/2025] [Indexed: 05/02/2025] Open
Abstract
Background Substantial impacts on the female reproductive system have been definitively linked to heightened levels of serum uric acid. However, evidence directly linking increased serum uric acid levels to endometriosis in women remains sparse, and the precise characteristics of this influence are still not fully understood. Objective To explore the exact relationship between serum uric acid and endometriosis. Study design Referencing the data accumulated from the National Health and Nutrition Examination Survey (NHANES), this study covers the period from 1999 to 2006, conducted an analysis of 5,162 female participants aged 20 to 54 years (representing a sample size of approximately 66,927,890 women). The study adopted a cross-sectional methodology to delve into the tie between serum uric acid and the prevalence of endometriosis. Utilizing rigorous methodologies, including weighted multivariable logistic regression models, subgroup analyses, and statistical methodologies for smooth curve fitting. Results A positive association was found between continuous serum uric acid and the risk of endometriosis (OR = 1.25, 95% CI [1.09, 1.44], P = 0.003). At the same time, women in the highest quartile had a 133% higher risk of endometriosis compared with women with the lowest quartile of uric acid (OR=2.33,95%CI [1.28, 4.23], P=0.009). At the same time, smooth curve fitting also found a linear positive correlation between serum uric acid and endometriosis. There was no heterogeneity in subgroup analysis. Conclusion The study indicates a strong link between increased serum uric acid levels and the appearance of endometriosis in women. Specifically, women with elevated uric acid levels face a higher likelihood of developing endometriosis.
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Affiliation(s)
- Haiwei Chen
- Department of Clinical Medicine, The Second Clinical College of Guangzhou Medical University, Guangzhou, China
| | - Yuling Chen
- Department of Clinical Medicine, The Second Clinical College of Guangzhou Medical University, Guangzhou, China
| | - Xiaotong Chen
- Department of Clinical Medicine, The Second Clinical College of Guangzhou Medical University, Guangzhou, China
| | - Lixin Tang
- Department of Clinical Medicine, The Second Clinical College of Guangzhou Medical University, Guangzhou, China
| | - Jiaqi Liu
- Department of Clinical Medicine, The Second Clinical College of Guangzhou Medical University, Guangzhou, China
| | - Wen-Jing Shi
- Department of Gynecology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
| | - Yu-Hua Ou
- Department of Gynecology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
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Ameho S, Klutstein M. The effect of chronic inflammation on female fertility. Reproduction 2025; 169:e240197. [PMID: 39932461 PMCID: PMC11896653 DOI: 10.1530/rep-24-0197] [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: 06/06/2024] [Revised: 02/02/2025] [Accepted: 02/11/2025] [Indexed: 02/13/2025]
Abstract
In brief Chronic inflammation causes serious medical conditions in many organs and tissues, including female fertility. Here we review the current literature, showing that chronic inflammation has a negative impact on oocyte quality, folliculogenesis, hormone production, immune signaling and other processes that affect fertility in females. Abstract Inflammation has key biological roles in the battle against pathogens and additional key processes in development and tissue homeostasis. However, when inflammation becomes chronic, it can become a serious medical concern. Chronic inflammation has been shown to contribute to the etiology and symptoms of serious medical conditions such as ulcerative colitis, cardiovascular diseases, endometriosis and various cancers. One of the less recognized symptoms associated with chronic inflammation is its effect on reproduction, specifically on female fertility. Here we review the current literature, showing that chronic inflammation has a negative impact on oocyte quality, folliculogenesis, hormone production, immune signaling and other processes that affect fertility in females. We discuss several factors involved in the etiology of chronic inflammation and its effect on female fertility. We also discuss possible mechanisms by which these effects may be mediated and how interventions may mitigate the effect of chronic inflammation. Finally, we discuss the notion that in many cases, the effect of chronic inflammation is tightly correlated with and resembles the effect of aging, drawing interesting parallels between these processes, possibly through the effect of aging-associated inflammaging.
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Affiliation(s)
| | - Michael Klutstein
- Institute of Biomedical and Oral Research, Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
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Park GW, Ataallahi M, Park KH. Stress level in companion dogs with and without atopic dermatitis. JOURNAL OF ANIMAL SCIENCE AND TECHNOLOGY 2025; 67:468-476. [PMID: 40264528 PMCID: PMC12010224 DOI: 10.5187/jast.2024.e28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 02/16/2024] [Accepted: 02/27/2024] [Indexed: 04/24/2025]
Abstract
Dogs with atopic dermatitis (AD) often exhibit behaviors such as scratching and rubbing. This discomfort may cause stress in affected dogs. Thus, we investigated the association between stress levels in companion dogs with and without AD using hair cortisol concentration (HCC). In total, 202 dogs were involved in this study, including bichon frise (24 AD, 38 non-AD, 5.3 ± 1.8 kg), maltese (17 AD, 51 non-AD, 3.4 ± 0.8 kg), and poodle (14 AD, 58 non-AD, 4.4 ± 1.4 kg). Hair samples were collected by the owners once from the dog's neck, close to the skin, using scissors from 2019 to 2023 in Korea. The HCC was determined using a commercial enzyme immunoassay kit. Based on these results, the HCC in bichon frise and poodle with AD were higher (p < 0.05) than those without AD. No difference (p > 0.05) in HCC was observed in maltese with AD and without AD. Pooled data showed a higher HCC (p < 0.05) in AD dogs compared to without AD dogs. The HCC in female bichon frise and female maltese with AD were higher (p < 0.05) than those without AD. Conversely, no differences (p > 0.05) in HCC were observed between AD and non-AD in male bichon frise and male maltese dogs. Higher (p < 0.05) HCC were observed between the AD and non-AD in female and male poodles. In conclusion, the AD condition in dogs can act as a stressor and analysis of HCC can help to better monitor the chronic stress level of dogs affected by AD.
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Affiliation(s)
- Geun-Woo Park
- Department of Animal Industry Convergence,
Kangwon National University, Chuncheon 24341, Korea
- CO-ANI, Chuncheon 24232,
Korea
| | - Mohammad Ataallahi
- Department of Animal Industry Convergence,
Kangwon National University, Chuncheon 24341, Korea
| | - Kyu-Hyun Park
- Department of Animal Industry Convergence,
Kangwon National University, Chuncheon 24341, Korea
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Lee J, Baek HS, Jo K, Kim MH, Lee JM, Chang SA, Lim DJ. The Impact of Physical Activity on Thyroid Health: Insights From Representative Data in Korea. J Clin Endocrinol Metab 2025; 110:e717-e727. [PMID: 38620035 DOI: 10.1210/clinem/dgae178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Indexed: 04/17/2024]
Abstract
CONTEXT Thyroid hormones are essential for energy metabolism related to thermogenesis and oxygen consumption. OBJECTIVE This study evaluated the potential association of thyroid function including thyroid peroxidase antibodies (TPOAb) with physical activity in nationally representative data. DESIGN/SETTING/PARTICIPANTS This retrospective cohort study used data from the Korean National Health and Nutrition Examination Survey between 2013 and 2015. Physical activity (PA) was assessed using metabolic equivalents based on the validated Korean version of the International Physical Activity Questionnaire Short Form. PA level was categorized into 3 groups of high, moderate, and low. Participants with abnormal thyroid function test, restricted activity, or previous history of thyroid disease were excluded in the study. RESULTS A total of 5372 participants was finally selected. The free T4 level was lowest in the low PA group, while TSH was not significantly different among the groups. TPOAb titers increased in the following order: moderate PA, low PA, and high PA. After adjustment for confounding factors, moderate PA was associated with a high T4 level and a decrease in TSH and TPOAb with significance. However, there were no significant changes in free T4, TSH, or TPOAb titer in the high PA group. In a subanalysis, females with moderate PA showed a significant decrease in TSH and TPOAb. In both males and females, insulin sensitivity was increased with moderate PA. In obese participants, TSH negatively correlated with PA, and free T4 levels decreased in the low PA. The sensitivity to thyroid hormone did not differ in our study. CONCLUSION The present study found an association between thyroid function and moderate PA. Therefore, moderate-intensity PA should be recommended to improve thyroid function.
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Affiliation(s)
- Jeongmin Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 03312, Republic of Korea
| | - Han-Sang Baek
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea
| | - Kwanhoon Jo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, 21431, Republic of Korea
| | - Min-Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 03312, Republic of Korea
| | - Jung Min Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 03312, Republic of Korea
| | - Sang Ah Chang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 03312, Republic of Korea
| | - Dong-Jun Lim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea
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Wang YC, Zhu HH, He LC, Yao YT, Zhang L, Xue XL, Li JY, Zhang L, Song B, Shi CH, Li YS, Gao Y, Yang JH, Xu YM. Proteome Profiling of Serum Reveals Pathological Mechanisms and Biomarker Candidates for Cerebral Small Vessel Disease. Transl Stroke Res 2025:10.1007/s12975-025-01332-6. [PMID: 39934548 DOI: 10.1007/s12975-025-01332-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 12/29/2024] [Accepted: 01/18/2025] [Indexed: 02/13/2025]
Abstract
Cerebral small vessel disease (CSVD) is a global brain disorder that is characterized by a series of clinical, neuroimaging, and neuropathological manifestations. However, the molecular pathophysiological mechanisms of CSVD have not been thoroughly investigated. Liquid chromatography-tandem mass spectrometry-based proteomics has broad application prospects in biomedicine. It is used to elucidate disease-related molecular processes and pathophysiological pathways, thus providing an important opportunity to explore the pathophysiological mechanisms of CSVD. Serum samples were obtained from 96 participants (58 with CSVD and 38 controls) consecutively recruited from The First Affiliated Hospital of Zhengzhou University. After removing high-abundance proteins, the serum samples were analyzed using high-resolution mass spectrometry. Bioinformatics methods were used for in-depth analysis of the obtained proteomic data, and the results were verified experimentally. Compared with the control group, 52 proteins were differentially expressed in the sera of the CSVD group. Furthermore, analyses indicated the involvement of these differentially expressed proteins in CSVD through participation in the overactivation of complement and coagulation cascades and dysregulation of insulin-like growth factor-binding proteins. The proteomic biomarker panel identified by the machine learning model combined with clinical features is expected to facilitate the diagnosis of CSVD (AUC = 0.947, 95% CI = 0.895-0.978). The study is the most in-depth study on CSVD proteomics to date and suggests that the overactivation of the complement cascade and the dysregulation of IGFBP on- IGF may be closely correlated with the occurrence and progression of CSVD, offering the potential to develop peripheral blood biomarkers and providing new insights into the biological basis of CSVD.
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Affiliation(s)
- Yun-Chao Wang
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- National Health Commission Key Laboratory of Prevention and Treatment of Cerebrovascular Diseases, Zhengzhou, Henan, China
- The First Affiliated Hospital of Zhengzhou University, 1 Jian-She East Road, Zhengzhou, 450000, Henan, China
| | - Hang-Hang Zhu
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- National Health Commission Key Laboratory of Prevention and Treatment of Cerebrovascular Diseases, Zhengzhou, Henan, China
- The First Affiliated Hospital of Zhengzhou University, 1 Jian-She East Road, Zhengzhou, 450000, Henan, China
| | - Liu-Chang He
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- National Health Commission Key Laboratory of Prevention and Treatment of Cerebrovascular Diseases, Zhengzhou, Henan, China
- The First Affiliated Hospital of Zhengzhou University, 1 Jian-She East Road, Zhengzhou, 450000, Henan, China
| | - Ya-Ting Yao
- Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
- The First Affiliated Hospital of Zhengzhou University, 1 Jian-She East Road, Zhengzhou, 450000, Henan, China
| | - Lei Zhang
- Clinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- The First Affiliated Hospital of Zhengzhou University, 1 Jian-She East Road, Zhengzhou, 450000, Henan, China
| | - Xin-Li Xue
- Clinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- The First Affiliated Hospital of Zhengzhou University, 1 Jian-She East Road, Zhengzhou, 450000, Henan, China
| | - Jing-Yi Li
- Clinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- The First Affiliated Hospital of Zhengzhou University, 1 Jian-She East Road, Zhengzhou, 450000, Henan, China
| | - Li Zhang
- Clinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- The First Affiliated Hospital of Zhengzhou University, 1 Jian-She East Road, Zhengzhou, 450000, Henan, China
| | - Bo Song
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- The First Affiliated Hospital of Zhengzhou University, 1 Jian-She East Road, Zhengzhou, 450000, Henan, China
| | - Chang-He Shi
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- The First Affiliated Hospital of Zhengzhou University, 1 Jian-She East Road, Zhengzhou, 450000, Henan, China
| | - Yu-Sheng Li
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- The First Affiliated Hospital of Zhengzhou University, 1 Jian-She East Road, Zhengzhou, 450000, Henan, China
| | - Yuan Gao
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
- The First Affiliated Hospital of Zhengzhou University, 1 Jian-She East Road, Zhengzhou, 450000, Henan, China.
| | - Jing-Hua Yang
- Clinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
- The First Affiliated Hospital of Zhengzhou University, 1 Jian-She East Road, Zhengzhou, 450000, Henan, China.
| | - Yu-Ming Xu
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
- National Health Commission Key Laboratory of Prevention and Treatment of Cerebrovascular Diseases, Zhengzhou, Henan, China.
- The First Affiliated Hospital of Zhengzhou University, 1 Jian-She East Road, Zhengzhou, 450000, Henan, China.
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Svedlund Eriksson E, Lantero Rodriguez M, Halvorsen B, Johansson I, Mårtensson AKF, Wilhelmson AS, Huse C, Ueland T, Aukrust P, Broch K, Gullestad L, Amundsen BH, Andersen GØ, Karlsson MCI, Hagberg Thulin M, Camponeschi A, Trompet D, Hammarsten O, Redfors B, Borén J, Omerovic E, Levin MC, Chagin AS, Dahl TB, Tivesten Å. Testosterone exacerbates neutrophilia and cardiac injury in myocardial infarction via actions in bone marrow. Nat Commun 2025; 16:1142. [PMID: 39910039 PMCID: PMC11799197 DOI: 10.1038/s41467-025-56217-x] [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: 03/14/2024] [Accepted: 01/13/2025] [Indexed: 02/07/2025] Open
Abstract
Men develop larger infarct sizes than women after a myocardial infarction (MI), but the mechanism underlying this sex difference is unknown. Here, we demonstrated that blood neutrophil counts post-MI were higher in male than female mice. Castration-induced testosterone deficiency reduced blood neutrophil counts to the level in females and increased survival post-MI. These effects were mimicked by Osterix-directed ablation of the androgen receptor in bone marrow (BM). Mechanistically, androgens downregulated the leukocyte retention factor CXCL12 in BM stromal cells. Post-hoc analysis of clinical trial data showed that neutrophilia was greater in men than women after reperfusion of first-time ST-elevation MI, and tocilizumab, an interleukin-6 receptor inhibitor, reduced blood neutrophil counts and infarct size to a greater extent in men than women. Our work reveals a previously unknown mechanism connecting testosterone with neutrophilia and MI injury via BM and identifies the importance of considering sex when developing anti-inflammatory strategies to treat MI.
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Affiliation(s)
- Elin Svedlund Eriksson
- Wallenberg Laboratory for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Marta Lantero Rodriguez
- Wallenberg Laboratory for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Bente Halvorsen
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Inger Johansson
- Wallenberg Laboratory for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Anna K F Mårtensson
- Wallenberg Laboratory for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Anna S Wilhelmson
- Wallenberg Laboratory for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
- The Finsen Laboratory, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
- Biotech Research and Innovation Centre (BRIC), Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Camilla Huse
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Thor Ueland
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Thrombosis Research Center (TREC), Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
| | - Pål Aukrust
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Kaspar Broch
- Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway
- K. G. Jebsen Cardiac Research Centre and Centre for Heart Failure Research, University of Oslo, Oslo, Norway
| | - Lars Gullestad
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway
- K. G. Jebsen Cardiac Research Centre and Centre for Heart Failure Research, University of Oslo, Oslo, Norway
| | - Brage Høyem Amundsen
- Clinic of Cardiology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway
- Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | | | - Mikael C I Karlsson
- Department of Microbiology, Tumor, and Cell Biology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
| | - Malin Hagberg Thulin
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Alessandro Camponeschi
- Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
- Department of Clinical Immunology and Transfusion Medicine, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Dana Trompet
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
| | - Ola Hammarsten
- Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
| | - Björn Redfors
- Wallenberg Laboratory for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Jan Borén
- Wallenberg Laboratory for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Elmir Omerovic
- Wallenberg Laboratory for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Malin C Levin
- Wallenberg Laboratory for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Andrei S Chagin
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Tuva B Dahl
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Åsa Tivesten
- Wallenberg Laboratory for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
- Department of Endocrinology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.
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Yan G, Li J, Su Y, Li G, Feng G, Liu J, Gao X, Zhou H. Risk factors analysis of hypokalemia after radical resection of esophageal cancer and establishment of a nomogram risk prediction model. Front Surg 2025; 11:1433751. [PMID: 39840263 PMCID: PMC11747289 DOI: 10.3389/fsurg.2024.1433751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Accepted: 12/20/2024] [Indexed: 01/23/2025] Open
Abstract
Objective This study aimed to explore the risk factors of hypokalemia after radical resection of esophageal cancer (EC) and establish a nomogram risk prediction model to evaluate hypokalemia risk after esophagectomy. Thus, this study provides a reference for the clinical development of intervention measures. Methods Clinical data of EC patients who underwent radical surgery from January 2020 to November 2022 in the First Affiliated Hospital of Guangxi Medical University were retrospectively collected. The relevant variables were screened using multivariate logistic regression analysis with IBM SPSS 25.0 and R 4.2.0 software, and a nomogram for predicting hypokalemia risk was established. The established nomogram was evaluated by receiver operating characteristic (ROC), calibration, and decision curves. The model was also internally validated by 1000 bootstrap resampling methods. Results After radical EC resection, the incidence rate of hypokalemia in 213 patients was 19.2% (41/213). The hemoglobin levels, total serum protein, serum albumin, calcium ion concentration, direct bilirubin, prothrombin time (PT), and activated partial thromboplastin time (APTT) were related (p < 0.05). The multivariate logistic analysis showed that the white blood cell count, serum albumin level, direct bilirubin, and operation time were risk factors for hypokalemia after radical EC resection (p < 0.05). The area under the ROC curve (AUC) was 0.764, demonstrating the good discriminative ability of the established nomogram for hypokalemia prediction. The calibration curve showed a good fit between the predicted and actual observed probabilities. The model maintained a high C-index in the internal validation (C-index = 0.758), supporting that the nomogram can be widely used for hypokalemia prediction. Conclusion The prediction model for hypokalemia risk with individualized scores based on the patient's white blood cell count, serum albumin level, direct bilirubin, and operation time can screen out high-risk patients who might develop hypokalemia. It is of certain reference value for clinicians to screen and follow up with patients with emphasis and to formulate preoperative and postoperative intervention strategies.
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Affiliation(s)
| | | | | | | | | | | | | | - Huafu Zhou
- Department of Cardio-Thoracic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
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Ortega MA, Fraile-Martinez O, García-Montero C, Diaz-Pedrero R, Lopez-Gonzalez L, Monserrat J, Barrena-Blázquez S, Alvarez-Mon MA, Lahera G, Alvarez-Mon M. Understanding immune system dysfunction and its context in mood disorders: psychoneuroimmunoendocrinology and clinical interventions. Mil Med Res 2024; 11:80. [PMID: 39681901 DOI: 10.1186/s40779-024-00577-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 11/01/2024] [Indexed: 12/18/2024] Open
Abstract
Mood disorders include a set of psychiatric manifestations of increasing prevalence in our society, being mainly represented by major depressive disorder (MDD) and bipolar disorder (BD). The etiopathogenesis of mood disorders is extremely complex, with a wide spectrum of biological, psychological, and sociocultural factors being responsible for their appearance and development. In this sense, immune system dysfunction represents a key mechanism in the onset and pathophysiology of mood disorders, worsening mainly the central nervous system (neuroinflammation) and the periphery of the body (systemic inflammation). However, these alterations cannot be understood separately, but as part of a complex picture in which different factors and systems interact with each other. Psychoneuroimmunoendocrinology (PNIE) is the area responsible for studying the relationship between these elements and the impact of mind-body integration, placing the immune system as part of a whole. Thus, the dysfunction of the immune system is capable of influencing and activating different mechanisms that promote disruption of the psyche, damage to the nervous system, alterations to the endocrine and metabolic systems, and disruption of the microbiota and intestinal ecosystem, as well as of other organs and, in turn, all these mechanisms are responsible for inducing and enhancing the immune dysfunction. Similarly, the clinical approach to these patients is usually multidisciplinary, and the therapeutic arsenal includes different pharmacological (for example, antidepressants, antipsychotics, and lithium) and non-pharmacological (i.e., psychotherapy, lifestyle, and electroconvulsive therapy) treatments. These interventions also modulate the immune system and other elements of the PNIE in these patients, which may be interesting to understand the therapeutic success or failure of these approaches. In this sense, this review aims to delve into the relationship between immune dysfunction and mood disorders and their integration in the complex context of PNIE. Likewise, an attempt will be made to explore the effects on the immune system of different strategies available in the clinical approach to these patients, in order to identify the mechanisms described and their possible uses as biomarkers.
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Affiliation(s)
- Miguel A Ortega
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcalá de Henares, Spain.
- Ramón y Cajal Institute of Sanitary Research IRYCIS, 28034, Madrid, Spain.
| | - Oscar Fraile-Martinez
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research IRYCIS, 28034, Madrid, Spain
| | - Cielo García-Montero
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcalá de Henares, Spain.
- Ramón y Cajal Institute of Sanitary Research IRYCIS, 28034, Madrid, Spain.
| | - Raul Diaz-Pedrero
- Ramón y Cajal Institute of Sanitary Research IRYCIS, 28034, Madrid, Spain
- Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcala de Henares, Spain
| | - Laura Lopez-Gonzalez
- Ramón y Cajal Institute of Sanitary Research IRYCIS, 28034, Madrid, Spain
- Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcala de Henares, Spain
| | - Jorge Monserrat
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research IRYCIS, 28034, Madrid, Spain
| | - Silvestra Barrena-Blázquez
- Ramón y Cajal Institute of Sanitary Research IRYCIS, 28034, Madrid, Spain
- Department of Nursing and Physiotherapy, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcalá de Henares, Spain
| | - Miguel Angel Alvarez-Mon
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research IRYCIS, 28034, Madrid, Spain
- Department of Psychiatry and Mental Health, Hospital Universitario Infanta Leonor, 28031, Madrid, Spain
| | - Guillermo Lahera
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research IRYCIS, 28034, Madrid, Spain
- Psychiatry Service, Center for Biomedical Research in the Mental Health Network, University Hospital Príncipe de Asturias, 28806, Alcalá de Henares, Spain
| | - Melchor Alvarez-Mon
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research IRYCIS, 28034, Madrid, Spain
- Immune System Diseases-Rheumatology and Internal Medicine Service, University Hospital Príncipe de Asturias, CIBEREHD, 28806, Alcalá de Henares, Spain
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Ma H, Sui GY, Park JS, Wang F, Ma Y, Shin DS, Rustamov N, Jang JS, Chang SI, Lee J, Roh YS. Blockade of 11β-hydroxysteroid dehydrogenase type 1 ameliorates metabolic dysfunction-associated steatotic liver disease and fibrosis. Heliyon 2024; 10:e39534. [PMID: 39498052 PMCID: PMC11534184 DOI: 10.1016/j.heliyon.2024.e39534] [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: 06/01/2024] [Revised: 10/16/2024] [Accepted: 10/16/2024] [Indexed: 11/07/2024] Open
Abstract
11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a key enzyme involved in the conversion of cortisone to active cortisol in the liver. Elevated cortisol levels can trigger oxidative stress, inflammation, and hepatocyte damage, highlighting the importance of 11β-HSD1 inhibition as a potential therapeutic approach. This study aimed to explore the effects of INU-101, an inhibitor of 11β-HSD1, on the development of metabolic dysfunction-associated steatotic liver disease (MASLD) and fibrosis. Our findings demonstrated that INU-101 effectively mitigated cortisol-induced lipid accumulation, reactive oxygen species generation, and hepatocyte apoptosis. Furthermore, 11β-HSD1 inhibition suppressed hepatic stellate cell activation by modulating β-catenin and phosphorylated SMAD2/3. INU-101 administration significantly reduced hepatic lipid accumulation and liver fibrosis in mice fed fast-food diet. This study suggests that INU-101 holds promise as a clinical candidate for treating MASLD and fibrosis, offering potential therapeutic benefits by targeting the intricate processes involving 11β-HSD1 and cortisol regulation in the liver.
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Affiliation(s)
- Hwan Ma
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, 28160, South Korea
| | - Guo-Yan Sui
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, 28160, South Korea
| | - Jeong-Su Park
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, 28160, South Korea
| | - Feng Wang
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, 28160, South Korea
| | - Yuanqiang Ma
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, 28160, South Korea
| | - Dong-Su Shin
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, 28160, South Korea
| | - Nodir Rustamov
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, 28160, South Korea
| | | | | | - Jin Lee
- Department of Pathology, School of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA
| | - Yoon Seok Roh
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, 28160, South Korea
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Deng Q, Deng J, Wei X, Shen L, Chen J, Bi K. Associations between peripheral thyroid sensitivity and all-cause and cardiovascular mortality in the US adults with metabolic syndrome. Front Med (Lausanne) 2024; 11:1460811. [PMID: 39323468 PMCID: PMC11422239 DOI: 10.3389/fmed.2024.1460811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Accepted: 08/29/2024] [Indexed: 09/27/2024] Open
Abstract
Background The relationship between peripheral sensitivity to thyroid hormones, as indicated by the ratio of free triiodothyronine (fT3) to free thyroxine (fT4) (fT3/fT4), and the prognosis of metabolic syndrome (MetS) remains unclear. Methods This study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2012. MetS was defined based on the criteria established by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III). Kaplan-Meier survival curves, restricted cubic spline (RCS) analysis, and Cox proportional hazards models were employed to investigate the association between peripheral thyroid sensitivity and mortality outcomes among adults with MetS. Results A total of 3,101 adult participants (1,594 males and 1,507 females; median age: 52.00 years) with MetS were included in the analysis. Multivariate Cox regression analysis revealed that elevated levels of fT4 were positively associated with increased risks of both all-cause and cardiovascular mortality in the MetS population [adjustedhazard ratio (aHR): 2.74, 95% confidence interval (CI): 1.94-3.87, p < 0.001 for all-cause mortality; aHR: 3.93, 95% CI: 2.07-7.45, p < 0.001 for cardiovascular mortality]. Conversely, higher levels of fT3 and the fT3/fT4 ratio were found to be protective factors, reducing the mortality risk in the MetS population (fT3: aHR: 0.76, 95% CI: 0.57-0.99, p = 0.046 for all-cause mortality; fT3/fT4 ratio: aHR: 0.75, 95% CI: 0.67-0.85, p < 0.001 for all-cause mortality; aHR: 0.66, 95% CI: 0.52-0.83, p < 0.001 for cardiovascular mortality). The fT3/fT4 ratio exhibited a nonlinear association with all-cause mortality, but a linear and inverse association with cardiovascular mortality. Conclusion The findings of this study suggest that higher peripheral thyroid sensitivity, as indicated by the fT3/fT4 ratio, may be associated with reduced mortality risks among adults with MetS. Further research is warranted to validate these associations.
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Affiliation(s)
- Qin Deng
- Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Juan Deng
- Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiaoyuan Wei
- Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Lu Shen
- Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jing Chen
- Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ke Bi
- Department of Emergency, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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12
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Straub RH, Cutolo M. A History of Psycho-Neuro-Endocrine Immune Interactions in Rheumatic Diseases. Neuroimmunomodulation 2024; 31:183-210. [PMID: 39168106 DOI: 10.1159/000540959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 08/15/2024] [Indexed: 08/23/2024] Open
Abstract
BACKGROUND All active scientists stand on the shoulders of giants and many other more anonymous scientists, and this is not different in our field of psycho-neuro-endocrine immunology in rheumatic diseases. Too often, the modern world of publishing forgets about the collective enterprise of scientists. Some journals advise the authors to present only literature from the last decade, and it has become a natural attitude of many scientists to present only the latest publications. In order to work against this general unempirical behavior, neuroimmunomodulation devotes the 30th anniversary issue to the history of medical science in psycho-neuro-endocrine immunology. SUMMARY Keywords were derived from the psycho-neuro-endocrine immunology research field very well known to the authors (R.H.S. has collected a list of keywords since 1994). We screened PubMed, the Cochran Library of Medicine, Embase, Scopus database, and the ORCID database to find relevant historical literature. The Snowballing procedure helped find related work. According to the historical appearance of discoveries in the field, the order of presentation follows the subsequent scheme: (1) the sensory nervous system, (2) the sympathetic nervous system, (3) the vagus nerve, (4) steroid hormones (glucocorticoids, androgens, progesterone, estrogens, and the vitamin D hormone), (5) afferent pathways involved in fatigue, anxiety, insomnia, and depression (includes pathophysiology), and (6) evolutionary medicine and energy regulation - an umbrella theory. KEY MESSAGES A brief history on psycho-neuro-endocrine immunology cannot address all relevant aspects of the field. The authors are aware of this shortcoming. The reader must see this review as a viewpoint through the biased eyes of the authors. Nevertheless, the text gives an overview of the history in psycho-neuro-endocrine immunology of rheumatic diseases.
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Affiliation(s)
- Rainer H Straub
- Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Department of Internal Medicine, University Hospital Regensburg, Regensburg, Germany
| | - Maurizio Cutolo
- Research Laboratories and Academic Division of Clinical Rheumatology, Department of Internal Medicine DIMI, Postgraduate School of Rheumatology, University of Genova, Genoa, Italy
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Rajaiah R, Pandey K, Acharya A, Ambikan A, Kumar N, Guda R, Avedissian SN, Montaner LJ, Cohen SM, Neogi U, Byrareddy SN. Differential immunometabolic responses to Delta and Omicron SARS-CoV-2 variants in golden syrian hamsters. iScience 2024; 27:110501. [PMID: 39171289 PMCID: PMC11338146 DOI: 10.1016/j.isci.2024.110501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 02/07/2024] [Accepted: 07/10/2024] [Indexed: 08/23/2024] Open
Abstract
Delta (B.1.617.2) and Omicron (B.1.1.529) variants of SARS-CoV-2 represents unique clinical characteristics. However, their role in altering immunometabolic regulations during acute infection remains convoluted. Here, we evaluated the differential immunopathogenesis of Delta vs. Omicron variants in Golden Syrian hamsters (GSH). The Delta variant resulted in higher virus titers in throat swabs and the lungs and exhibited higher lung damage with immune cell infiltration than the Omicron variant. The gene expression levels of immune mediators and metabolic enzymes, Arg-1 and IDO1 in the Delta-infected lungs were significantly higher compared to Omicron. Further, Delta/Omicron infection perturbed carbohydrates, amino acids, nucleotides, and TCA cycle metabolites and was differentially regulated compared to uninfected lungs. Collectively, our data provide a novel insight into immunometabolic/pathogenic outcomes for Delta vs. Omicron infection in the GSH displaying concordance with COVID-19 patients associated with inflammation and tissue injury during acute infection that offered possible new targets to develop potential therapeutics.
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Affiliation(s)
- Rajesh Rajaiah
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA
| | - Kabita Pandey
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA
| | - Arpan Acharya
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA
| | - Anoop Ambikan
- The Systems Virology Lab, Department of Laboratory Medicine, Division of Clinical Microbiology, ANA Futura, Karolinska Institutet, 141 52 Stockholm, Sweden
| | - Narendra Kumar
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA
| | - Reema Guda
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA
| | - Sean N. Avedissian
- Antiviral Pharmacology Laboratory, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA
| | - Luis J. Montaner
- Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA
| | - Samuel M. Cohen
- Havlik Wall Professor of Oncology, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Ujjwal Neogi
- The Systems Virology Lab, Department of Laboratory Medicine, Division of Clinical Microbiology, ANA Futura, Karolinska Institutet, 141 52 Stockholm, Sweden
| | - Siddappa N. Byrareddy
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA
- Havlik Wall Professor of Oncology, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA
- Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
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14
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Zaegel N, Brahimaj R, Battaglia-Hsu S, Lamiral Z, Feigerlova E. Systemic Inflammatory Indices and Liver Dysfunction in Turner Syndrome Patients: A Retrospective Case-control Study. J Endocr Soc 2024; 8:bvae099. [PMID: 38831865 PMCID: PMC11145559 DOI: 10.1210/jendso/bvae099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Indexed: 06/05/2024] Open
Abstract
Context Liver function abnormalities have been reported in patients with Turner syndrome (TS); however, the pathophysiological mechanisms have not been well elucidated. Low-grade inflammation has been associated with metabolic dysfunction-associated steatotic liver disease. Objective We studied systemic inflammatory indices [aspartate transaminase to lymphocyte ratio index (ALRI), aspartate transaminase to platelet ratio index (APRI), gamma-glutamyl transferase to platelet ratio (GPR), neutrophil-lymphocyte-ratio (NLR), and platelet lymphocyte ratio and examined their associations with the hepatic abnormalities observed in these subjects. Methods We performed a retrospective analysis of the medical records of 79 patients with TS (mean age 32.5 ± 9.2 SD years) who were treated at the University Hospital of Nancy. Using matched-pair analyses based on age and body mass index (BMI), we compared 66 patients with TS (25.6 ± 7.3 years; BMI 25.9 ± 6.3 kg/m2) to 66 healthy control participants (24.7 ± 6.8 years; BMI 26 ± 6.7 kg/m2). Results Liver function abnormalities were present in 57% of the patients with TS. The ALRI, APRI, GPR, and NLR were significantly greater in patients with TS who presented with liver dysfunction than in patients with TS who had normal liver function. According to the matched-pair analyses, the ALRI, APRI, and GPR were greater in patients with TS than in healthy control participants. Logistic regression revealed that a diagnosis of TS was significantly associated with ALRI, APRI, and GPR and liver dysfunction. Conclusion Noninvasive inflammatory indices (ALRI, APRI, and GPR) might be a promising indicators of liver dysfunction in patients with TS. Future prospective studies are needed to confirm our findings and to explore the clinical significance and prognostic value of systemic inflammatory indices in Turner syndrome.
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Affiliation(s)
- Nadia Zaegel
- Department of Endocrinology, Diabetology and Nutrition, Centre Hospitalier Universitaire and Medical Faculty, Université de Lorraine, Nancy 54000, France
| | - Rigleta Brahimaj
- Department of Endocrinology, Diabetology and Nutrition, Centre Hospitalier Universitaire and Medical Faculty, Université de Lorraine, Nancy 54000, France
| | - Shyuefang Battaglia-Hsu
- Department of Biochemistry, Centre Hospitalier Universitaire and Medical Faculty, Université de Lorraine, Nancy 54000, France
| | - Zohra Lamiral
- Center of Clinical Investigation, Centre Hospitalier Universitaire, Nancy 54000, France
| | - Eva Feigerlova
- Department of Endocrinology, Diabetology and Nutrition, Centre Hospitalier Universitaire and Medical Faculty, Université de Lorraine, Nancy 54000, France
- INSERM UMR_S 1116—DCAC, Université de Lorraine, Nancy 54000, France
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Furgoł T, Antończyk R, Miciak M, Jezierzański M, Smreczak M, Gigoń K, Fogiel O, Ratajczak M, Hrapkowicz T. Inflammatory response induction as a result of BioGlue adhesive application in cardiac surgery - a review of the literature. KARDIOCHIRURGIA I TORAKOCHIRURGIA POLSKA = POLISH JOURNAL OF CARDIO-THORACIC SURGERY 2024; 21:43-46. [PMID: 38693976 PMCID: PMC11059011 DOI: 10.5114/kitp.2024.138566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 03/07/2024] [Indexed: 05/03/2024]
Abstract
BioGlue is one of the best-known substances used as a tissue adhesive during surgical procedures, especially in cardiac surgery. Inappropriate use of BioGlue can result in inflammation in both the heart and adjacent tissues after its intraoperative application. Inflammation caused by BioGlue in cardiac surgery is a topic that has been discussed by numerous authors in scientific studies, meta-analyses and evaluations of this tissue adhesive. However, there is a lack of collected knowledge on this subject in a single concise article. The purpose of this paper is to review the current medical knowledge on the use of BioGlue in cardiac surgery versus the induction of an inflammatory response. Our paper discusses the details of this problem according to the most recent scientific reports.
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Affiliation(s)
- Tomasz Furgoł
- Student’s Scientific Society, Department of Cardiac Surgery, Transplantology, Vascular and Endovascular Surgery, School of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Poland
| | - Remigiusz Antończyk
- Department of Cardiac Surgery, Transplantology, Vascular and Endovascular Surgery, School of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Poland
| | - Michał Miciak
- Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - Marcin Jezierzański
- Student’s Scientific Society, Department of Cardiac Surgery, Transplantology, Vascular and Endovascular Surgery, School of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Poland
| | - Maciej Smreczak
- Student’s Scientific Society, Department of Cardiac Surgery, Transplantology, Vascular and Endovascular Surgery, School of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Poland
| | - Konrad Gigoń
- Student’s Scientific Society, Department of Cardiac Surgery, Transplantology, Vascular and Endovascular Surgery, School of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Poland
| | - Oskar Fogiel
- Student’s Scientific Society, Department of Cardiac Surgery, Transplantology, Vascular and Endovascular Surgery, School of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Poland
| | - Maksymilian Ratajczak
- Student’s Scientific Society, Department of Cardiac Surgery, Transplantology, Vascular and Endovascular Surgery, School of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Poland
| | - Tomasz Hrapkowicz
- Department of Cardiac Surgery, Transplantology, Vascular and Endovascular Surgery, School of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Poland
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Uccella S, Dottermusch M, Erickson L, Warmbier J, Montone K, Saeger W. Inflammatory and Infectious Disorders in Endocrine Pathology. Endocr Pathol 2023; 34:406-436. [PMID: 37209390 PMCID: PMC10199304 DOI: 10.1007/s12022-023-09771-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/03/2023] [Indexed: 05/22/2023]
Abstract
A variety of inflammatory conditions may directly involve the endocrine glands, leading to endocrine dysfunction that can cause severe consequences on patients' health, if left untreated. Inflammation of the endocrine system may be caused by either infectious agents or other mechanisms, including autoimmune and other immune-mediated processes. Not infrequently, inflammatory and infectious diseases may appear as tumor-like lesions of endocrine organs and simulate neoplastic processes. These diseases may be clinically under-recognized and not infrequently the diagnosis is suggested on pathological samples. Thus, the pathologist should be aware of the basic principles of their pathogenesis, as well as of their morphological features, clinicopathological correlates, and differential diagnosis. Interestingly, several systemic inflammatory conditions show a peculiar tropism to the endocrine system as a whole. In turn, organ-specific inflammatory disorders are observed in endocrine glands. This review will focus on the morphological aspects and clinicopathological features of infectious diseases, autoimmune disorders, drug-induced inflammatory reactions, IgG4-related disease, and other inflammatory disorders involving the endocrine system. A mixed entity-based and organ-based approach will be used, with the aim to provide the practicing pathologist with a comprehensive and practical guide to the diagnosis of infectious and inflammatory disorders of the endocrine system.
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Affiliation(s)
- Silvia Uccella
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanule, Milan, Italy
- Pathology Service IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Matthias Dottermusch
- Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Lori Erickson
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN USA
| | - Julia Warmbier
- Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Kathleen Montone
- Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA USA
| | - Wolfgang Saeger
- Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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17
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Schmid A, Karrasch T, Schäffler A. The emerging role of bile acids in white adipose tissue. Trends Endocrinol Metab 2023; 34:718-734. [PMID: 37648561 DOI: 10.1016/j.tem.2023.08.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 07/21/2023] [Accepted: 08/02/2023] [Indexed: 09/01/2023]
Abstract
The effects of bile acids (BAs) on liver, enteroendocrine function, small intestine, and brown adipose tissue have been described extensively. Outside the liver, BAs in the peripheral circulation system represent a specific but underappreciated physiological compartment. We discuss how systemic BAs can be regarded as specific steroidal hormones that act on white adipocytes, and suggest the name 'bilokines' ('bile hormones') for the specific FXR/TGR5 receptor interaction in adipocytes. Some BAs and their agonists regulate adipocyte differentiation, lipid accumulation, hypoxia, autophagy, adipokine and cytokine secretion, insulin signaling, and glucose uptake. BA signaling could provide a new therapeutic avenue for adipoflammation and metaflammation in visceral obesity, the causal mechanisms underlying insulin resistance and type 2 diabetes mellitus (T2D).
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Affiliation(s)
- Andreas Schmid
- Basic Research Laboratory for Molecular Endocrinology, Adipocyte Biology, and Biochemistry, University of Giessen, D 35392 Giessen, Germany
| | - Thomas Karrasch
- Department of Internal Medicine III - Endocrinology, Diabetology, and Metabolism, University of Giessen, D 35392 Giessen, Germany
| | - Andreas Schäffler
- Department of Internal Medicine III - Endocrinology, Diabetology, and Metabolism, University of Giessen, D 35392 Giessen, Germany.
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18
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Straub RH, Pongratz G, Buttgereit F, Gaber T. [Energy metabolism of the immune system : Consequences in chronic inflammation]. Z Rheumatol 2023:10.1007/s00393-023-01389-4. [PMID: 37488246 DOI: 10.1007/s00393-023-01389-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/13/2023] [Indexed: 07/26/2023]
Abstract
BACKGROUND Energy is the currency of life. The systemic and intracellular energy metabolism plays an essential role for the energy supply of the resting and activated immune system and this also applies to chronic inflammatory diseases. OBJECTIVE This presentation examines both components of the systemic and cellular energy metabolism in health and chronic inflammation. MATERIAL AND METHODS A literature search was conducted using PubMed, Embase and the Cochrane Library. The information is presented in the form of a narrative review. RESULTS A chronically activated immune system acquires large amounts of energy-rich substrates that are lost for other functions of the body. In particular, the immune system and the brain are in competition. The consequences of this competition are many known diseases, such as fatigue, anxiety, depression, anorexia, sleep problems, sarcopenia, osteoporosis, insulin resistance, hypertension and others. The permanent change in the brain causes long-term alterations that stimulate disease sequelae even after disease remission. In the intracellular energy supply, chronic inflammation typically involves a conversion to glycolysis (to lactate, which has its own regulatory functions) and the pentose phosphate pathway in disorders of mitochondrial function. The chronic changes in immune cells of patients with rheumatoid arthritis (RA) lead to a disruption of the citric acid cycle (Krebs cycle). The hypoxic situation in the inflamed tissue stimulates many alterations. A differentiation is made between effector functions and regulatory functions of immune cells. CONCLUSION Based on the energy changes mentioned, novel treatment suggestions can be made in addition to those already known in energy metabolism.
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Affiliation(s)
- Rainer H Straub
- Labor für Experimentelle Rheumatologie und Neuroendokrin-Immunologie, Klinik und Poliklinik für Innere Medizin I, Universitätsklinikum Regensburg, 93042, Regensburg, Deutschland.
| | - Georg Pongratz
- Abteilung für Rheumatologie, Klinik für Gastroenterologie, Krankenhaus Barmherzige Brüder Regensburg, 93049, Regensburg, Deutschland
| | - Frank Buttgereit
- Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Charité - Universitätsmedizin Berlin, Freie Universität Berlin und Humboldt-Universität zu Berlin, Berlin, Deutschland
| | - Timo Gaber
- Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Charité - Universitätsmedizin Berlin, Freie Universität Berlin und Humboldt-Universität zu Berlin, Berlin, Deutschland
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19
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Ortega MA, Fraile-Martinez O, García-Montero C, Haro S, Álvarez-Mon MÁ, De Leon-Oliva D, Gomez-Lahoz AM, Monserrat J, Atienza-Pérez M, Díaz D, Lopez-Dolado E, Álvarez-Mon M. A comprehensive look at the psychoneuroimmunoendocrinology of spinal cord injury and its progression: mechanisms and clinical opportunities. Mil Med Res 2023; 10:26. [PMID: 37291666 PMCID: PMC10251601 DOI: 10.1186/s40779-023-00461-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Accepted: 06/01/2023] [Indexed: 06/10/2023] Open
Abstract
Spinal cord injury (SCI) is a devastating and disabling medical condition generally caused by a traumatic event (primary injury). This initial trauma is accompanied by a set of biological mechanisms directed to ameliorate neural damage but also exacerbate initial damage (secondary injury). The alterations that occur in the spinal cord have not only local but also systemic consequences and virtually all organs and tissues of the body incur important changes after SCI, explaining the progression and detrimental consequences related to this condition. Psychoneuroimmunoendocrinology (PNIE) is a growing area of research aiming to integrate and explore the interactions among the different systems that compose the human organism, considering the mind and the body as a whole. The initial traumatic event and the consequent neurological disruption trigger immune, endocrine, and multisystem dysfunction, which in turn affect the patient's psyche and well-being. In the present review, we will explore the most important local and systemic consequences of SCI from a PNIE perspective, defining the changes occurring in each system and how all these mechanisms are interconnected. Finally, potential clinical approaches derived from this knowledge will also be collectively presented with the aim to develop integrative therapies to maximize the clinical management of these patients.
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Affiliation(s)
- Miguel A. Ortega
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Oscar Fraile-Martinez
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Cielo García-Montero
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Sergio Haro
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Miguel Ángel Álvarez-Mon
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
- Department of Psychiatry and Mental Health, Hospital Universitario Infanta Leonor, 28031 Madrid, Spain
| | - Diego De Leon-Oliva
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Ana M. Gomez-Lahoz
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Jorge Monserrat
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Mar Atienza-Pérez
- Service of Rehabilitation, National Hospital for Paraplegic Patients, Carr. de la Peraleda, S/N, 45004 Toledo, Spain
| | - David Díaz
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Elisa Lopez-Dolado
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Department of Psychiatry and Mental Health, Hospital Universitario Infanta Leonor, 28031 Madrid, Spain
| | - Melchor Álvarez-Mon
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
- Immune System Diseases-Rheumatology Service and Internal Medicine, University Hospital Príncipe de Asturias (CIBEREHD), 28806 Alcala de Henares, Spain
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20
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Infante M, Pieri M, Lupisella S, Mohamad A, Bernardini S, Della-Morte D, Fabbri A, De Stefano A, Iannetta M, Ansaldo L, Crea A, Andreoni M, Morello M. Admission eGFR predicts in-hospital mortality independently of admission glycemia and C-peptide in patients with type 2 diabetes mellitus and COVID-19. Curr Med Res Opin 2023; 39:505-516. [PMID: 36749566 DOI: 10.1080/03007995.2023.2177380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 01/27/2023] [Accepted: 01/31/2023] [Indexed: 02/08/2023]
Abstract
OBJECTIVE Type 2 diabetes mellitus (T2DM) and impaired kidney function are associated with a higher risk of poor outcomes of coronavirus disease 2019 (COVID-19). We conducted a retrospective study in hospitalized T2DM patients with COVID-19 to assess the association between in-hospital mortality and admission values of different hematological/biochemical parameters, including estimated glomerular filtration rate (eGFR), plasma glucose and C-peptide (the latter serving as a marker of beta-cell function). METHODS The study included T2DM patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who were consecutively admitted to our Institution between 1 October 2020 and 1 April 2021. RESULTS Patients (n = 74) were categorized into survivors (n = 55) and non-survivors (n = 19). Non-survivors exhibited significantly higher median white blood cell (WBC) count, D-dimer, neutrophil-to-lymphocyte ratio, high-sensitivity C-reactive protein (hsCRP), and procalcitonin levels, as well as significantly lower median serum 25-hydroxyvitamin D [25(OH)D] levels compared to survivors. Non-survivors exhibited significantly higher median admission plasma glucose (APG) values compared to survivors (210 vs. 166 mg/dL; p = .026). There was no statistically significant difference in median values of (random) plasma C-peptide between non-survivors and survivors (3.55 vs. 3.24 ng/mL; p = .906). A significantly higher percentage of patients with an eGFR < 60 mL/min/1.73 m2 was observed in the non-survivor group as compared to the survivor group (57.9% vs. 23.6%; p = .006). A multivariate analysis performed by a logistic regression model after adjusting for major confounders (age, sex, body mass index, major comorbidities) showed a significant inverse association between admission eGFR values and risk of in-hospital mortality (OR, 0.956; 95% CI, 0.931-0.983; p = .001). We also found a significant positive association between admission WBC count and risk of in-hospital mortality (OR, 1.210; 95% CI, 1.043-1.404; p = .011). CONCLUSIONS Admission eGFR and WBC count predict in-hospital COVID-19 mortality among T2DM patients, independently of traditional risk factors, APG and random plasma C-peptide. Hospitalized patients with COVID-19 and comorbid T2DM associated with impaired kidney function at admission should be considered at high risk for adverse outcomes and death.
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Affiliation(s)
- Marco Infante
- Department of Systems Medicine & Diabetes Research Institute Federation (DRIF), University of Rome Tor Vergata, Rome, Italy
- Section of Diabetes and Metabolic Disorders, UniCamillus, Saint Camillus International University of Health Sciences, Rome, Italy
- Cell Transplant Center, Diabetes Research Institute (DRI), University of Miami Miller School of Medicine, Miami, FL, USA
| | - Massimo Pieri
- Department of Experimental Medicine, Clinical Biochemistry and Molecular Biology, Faculty of Medicine, University of Rome Tor Vergata, Rome, Italy
- Clinical Biochemistry Department, Tor Vergata University Hospital (PTV), Rome, Italy
| | - Santina Lupisella
- Clinical Biochemistry Department, Tor Vergata University Hospital (PTV), Rome, Italy
| | - Ali Mohamad
- Clinical Biochemistry Department, Tor Vergata University Hospital (PTV), Rome, Italy
| | - Sergio Bernardini
- Department of Experimental Medicine, Clinical Biochemistry and Molecular Biology, Faculty of Medicine, University of Rome Tor Vergata, Rome, Italy
- Clinical Biochemistry Department, Tor Vergata University Hospital (PTV), Rome, Italy
| | - David Della-Morte
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Andrea Fabbri
- Department of Systems Medicine & Diabetes Research Institute Federation (DRIF), University of Rome Tor Vergata, Rome, Italy
| | - Alberto De Stefano
- Psychiatry Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Volunteers Association, Tor Vergata University Hospital (PTV), Rome, Italy
| | - Marco Iannetta
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Infectious Disease Clinic, Tor Vergata University Hospital (PTV), Rome, Italy
| | - Lorenzo Ansaldo
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Infectious Disease Clinic, Tor Vergata University Hospital (PTV), Rome, Italy
| | - Angela Crea
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Infectious Disease Clinic, Tor Vergata University Hospital (PTV), Rome, Italy
| | - Massimo Andreoni
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Infectious Disease Clinic, Tor Vergata University Hospital (PTV), Rome, Italy
| | - Maria Morello
- Department of Experimental Medicine, Clinical Biochemistry and Molecular Biology, Faculty of Medicine, University of Rome Tor Vergata, Rome, Italy
- Clinical Biochemistry Department, Tor Vergata University Hospital (PTV), Rome, Italy
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21
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ELbialy ZI, Atef E, Al-Hawary II, Salah AS, Aboshosha AA, Abualreesh MH, Assar DH. Myostatin-mediated regulation of skeletal muscle damage post-acute Aeromonas hydrophila infection in Nile tilapia (Oreochromis niloticus L.). FISH PHYSIOLOGY AND BIOCHEMISTRY 2023; 49:1-17. [PMID: 36622623 DOI: 10.1007/s10695-022-01165-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 12/20/2022] [Indexed: 06/17/2023]
Abstract
This study focuses on the relationship between myostatin (MyoS), myogenin (MyoG), and the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis for muscle growth and histopathological changes in muscle after an Aeromonas hydrophila infection. A total number of 90 Nile tilapia (55.85 g) were randomly allocated into two equal groups of three replicates each. The first group was an uninfected control group that was injected intraperitoneally (ip) with 0.2 ml phosphate buffer saline (PBS), while the second group was injected ip with 0.2 ml (1.3 × 108 CFU/ml) Aeromonas hydrophila culture suspension. Sections of white muscle and liver tissues were taken from each group 24 h, 48 h, 72 h, and 1 week after infection for molecular analysis and histopathological examination. The results revealed that with time progression, the severity of muscle lesions increased from edema between bundles and mononuclear inflammatory cell infiltration 24 h post-challenge to severe atrophy of muscle bundles with irregular and curved fibers with hyalinosis of the fibers 1 week postinfection. The molecular analysis showed that bacterial infection was able to induce the muscle expression levels of GH with reduced ILGF-1, MyoS, and MyoG at 24 h postinfection. However, time progression postinfection reversed these findings through elevated muscle expression levels of MyoS with regressed expression levels of muscle GH, ILGF-1, and MyoG. There have been no previous reports on the molecular expression analysis of the aforementioned genes and muscle histopathological changes in Nile tilapia following acute Aeromonas hydrophila infection. Our findings, collectively, revealed that the up-and down-regulation of the myostatin signaling is likely to be involved in the postinfection-induced muscle wasting through the negative regulation of genes involved in muscle growth, such as GH, ILGF-1, and myogenin, in response to acute Aeromonas hydrophila infection in Nile tilapia, Oreochromis niloticus.
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Affiliation(s)
- Zizy I ELbialy
- Fish Processing and Biotechnology Department, Faculty of Aquatic and Fisheries Sciences, Kafrelsheikh University, Kafrelsheikh, 33516, Egypt.
| | - Eman Atef
- Fish Processing and Biotechnology Department, Faculty of Aquatic and Fisheries Sciences, Kafrelsheikh University, Kafrelsheikh, 33516, Egypt
| | - Ibrahim I Al-Hawary
- Fish Processing and Biotechnology Department, Faculty of Aquatic and Fisheries Sciences, Kafrelsheikh University, Kafrelsheikh, 33516, Egypt
| | - Abdallah S Salah
- Department of Aquaculture, Faculty of Aquatic and Fisheries Sciences, Kafrelsheikh University, Kafrelsheikh, 33516, Egypt
- Institute of Aquaculture, Faculty of Natural Sciences, University of Stirling, Stirling, FK9 4LA, UK
| | - Ali A Aboshosha
- Department of Genetics, Faculty of Agriculture, Kafrelsheikh University, Kafrelsheikh, 33516, Egypt
| | - Muyassar H Abualreesh
- Department of Marine Biology, Faculty of Marine Sciences, King Abdul-Aziz University (KAU), Jeddah, 21589, Saudi Arabia
| | - Doaa H Assar
- Clinical Pathology Department, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, 33516, Egypt.
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22
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Abstract
Sickness behavior was conceptualized initially as the behavioral counterpart of the fever response to infectious pathogens. It helps to raise body temperature to its higher setpoint and to maintain it at this new level and it has the additional benefit of enabling a weakened organism to protect itself from other dangers. The discovery of the behavioral effects of proinflammatory cytokines produced by activated immune cells provided a cellular and molecular basis to this phenomenon. The administration of cytokines or cytokine inducers like lipopolysaccharide to healthy rodents allowed to reveal the similarities and differences between inflammation-induced sickness behavior and the fever response. It also led to the understanding of how the inflammatory response that is triggered at the periphery can propagate into the brain and induce the behavioral manifestations of sickness. At the behavioral level, the demonstration that sickness behavior is the expression of a motivational state that reorganizes perception and action in face of a microbial pathogen just like fear in face of a predator appeared at first glance to strengthen the adaptive value of this behavior. However, all aspects of sickness behavior are not always favorable for the organism. This is the case for anorexia that is beneficial in the context of bacterial infection but detrimental in the context of viral infection. In addition, studies of sickness behavior in natural conditions revealed that like any other defensive behavior, sickness behavior requires trade-offs between its survival benefits for the sick individual and the costs incurred especially in the context of gregarious groups. Thanks to these studies, evidence is emerging that sickness behavior is much more variable in its expression than initially thought, and that part of this variability depends not only on the pathogen and the social context in which the infection develops but also on individual factors including species, sex, age, nutrition, and physiological status.
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Affiliation(s)
- Robert Dantzer
- Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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23
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Fraile-Martinez O, Alvarez-Mon MA, Garcia-Montero C, Pekarek L, Guijarro LG, Lahera G, Saez MA, Monserrat J, Motogo D, Quintero J, Alvarez-Mon M, Ortega MA. Understanding the basis of major depressive disorder in oncological patients: Biological links, clinical management, challenges, and lifestyle medicine. Front Oncol 2022; 12:956923. [PMID: 36185233 PMCID: PMC9524231 DOI: 10.3389/fonc.2022.956923] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 08/23/2022] [Indexed: 12/03/2022] Open
Abstract
In recent years, the incidence of different types of cancer and patient survival have been rising, as well as their prevalence. The increase in survival in recent years exposes the patients to a set of stressful factors such as more rigorous follow-up and more aggressive therapeutic regimens that, added to the diagnosis of the disease itself, cause an increase in the incidence of depressive disorders. These alterations have important consequences for the patients, reducing their average survival and quality of life, and for these reasons, special emphasis has been placed on developing numerous screening tests and early recognition of depressive symptoms. Despite that cancer and major depressive disorder are complex and heterogeneous entities, they also share many critical pathophysiological mechanisms, aiding to explain this complex relationship from a biological perspective. Moreover, a growing body of evidence is supporting the relevant role of lifestyle habits in the prevention and management of both depression and cancer. Therefore, the present study aims to perform a thorough review of the intricate relationship between depression and cancer, with a special focus on its biological links, clinical management, challenges, and the central role of lifestyle medicine as adjunctive and preventive approaches to improve the quality of life of these patients.
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Affiliation(s)
- Oscar Fraile-Martinez
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
| | - Miguel A. Alvarez-Mon
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Department of Psychiatry and Mental Health, Hospital Universitario Infanta Leonor, Madrid, Spain
- *Correspondence: Miguel A. Alvarez-Mon, ;
| | - Cielo Garcia-Montero
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
| | - Leonel Pekarek
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Oncology Service, Guadalajara University Hospital, Guadalajara, Spain
| | - Luis G. Guijarro
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Unit of Biochemistry and Molecular Biology, Department of System Biology, Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas (CIBEREHD), University of Alcalá, Alcala de Henares, Spain
| | - Guillermo Lahera
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Psychiatry Service, Center for Biomedical Research in the Mental Health Network, University Hospital Príncipe de Asturias Centro de Investigación Biomédica en Red en el Área temática de Salud Mental (CIBERSAM), Alcalá de Henares, Spain
| | - Miguel A. Saez
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Pathological Anatomy Service, Central University Hospital of Defence-UAH Madrid, Alcala de Henares, Spain
| | - Jorge Monserrat
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
| | - Domitila Motogo
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, Spain
| | - Javier Quintero
- Department of Psychiatry and Mental Health, Hospital Universitario Infanta Leonor, Madrid, Spain
- Department of Legal Medicine and Psychiatry, Complutense University, Madrid, Spain
| | - Melchor Alvarez-Mon
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Immune System Diseases-Rheumatology, Oncology Service an Internal Medicine, Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas (CIBEREHD), University Hospital Príncipe de Asturias, Alcala de Henares, Spain
| | - Miguel A. Ortega
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Cancer Registry and Pathology Department, Principe de Asturias University Hospital, Alcala de Henares, Spain
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Arustamyan M, Kibrik P, Hatipoglu D, Bungo B, Mentias A, Hill BT, Moudgil R. The Safety of Bruton's Tyrosine Kinase Inhibitors in B-cell Malignancies: A Systematic Review. Eur J Haematol 2022; 109:696-710. [PMID: 36030394 DOI: 10.1111/ejh.13854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 08/17/2022] [Accepted: 08/19/2022] [Indexed: 12/01/2022]
Abstract
B-cell malignancies, most notably lymphomas, make up most of the non-Hodgkin lymphomas in the United States. There is limited randomized data comparing 1st and 2nd generation Bruton Tyrosine Kinase inhibitors. Our aim was to compare the safety profiles of 1st versus 2nd generation Bruton Tyrosine Kinase inhibitors. A systematic search was performed from database inception to January 13, 2020. Studies with Bruton Tyrosine Kinase inhibitor monotherapy for the treatment of B-cell malignancies in the adult population (> 18 years old) were utilized and the adverse events were extracted. Fifty-five studies that met the inclusion criteria were included in the systematic review with forty-one studies with 1st generation and fourteen studies with 2nd generation. The review included both clinical trials and retrospective studies with average time of follow-up of 2 years for the 1st generation group and 18 months for the 2nd generation group. We found that the incidence of cardiovascular adverse events was significantly higher in the 1st generation group (20.8%) as compared to the 2nd generation group (6.3%). However, there was a higher incidence of hematologic/oncologic and gastrointestinal side effects in the 2nd generation group compared to the 1st (62.3% compared to 39.2% and 36.9% compare to 28.9%). The number of Grade 5 cardiovascular events (death) were same in the 1st generation group compared to the 2nd generation. Further research is needed to develop highly selective Bruton Tyrosine Kinase inhibitors to avoid unwanted adverse events by minimizing off-targets. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Michael Arustamyan
- Section of Clinical Cardiology, Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Section of Leukemia/Lymphoma, Department of Hematology and Medical Oncology
| | - Pavel Kibrik
- Section of Clinical Cardiology, Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Section of Leukemia/Lymphoma, Department of Hematology and Medical Oncology
| | - Dilara Hatipoglu
- Section of Clinical Cardiology, Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Section of Leukemia/Lymphoma, Department of Hematology and Medical Oncology
| | - Brandon Bungo
- Section of Clinical Cardiology, Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Section of Leukemia/Lymphoma, Department of Hematology and Medical Oncology.,Taussig Cancer Institute and Case Comprehensive Cancer Center, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH
| | - Amgad Mentias
- Section of Clinical Cardiology, Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Section of Leukemia/Lymphoma, Department of Hematology and Medical Oncology
| | - Brian T Hill
- Taussig Cancer Institute and Case Comprehensive Cancer Center, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH
| | - Rohit Moudgil
- Section of Clinical Cardiology, Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Section of Leukemia/Lymphoma, Department of Hematology and Medical Oncology
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Ortega MA, García-Montero C, Fraile-Martinez O, Alvarez-Mon MA, Gómez-Lahoz AM, Lahera G, Monserrat J, Rodriguez-Jimenez R, Quintero J, Álvarez-Mon M. Immune-Mediated Diseases from the Point of View of Psychoneuroimmunoendocrinology. BIOLOGY 2022; 11:973. [PMID: 36101354 PMCID: PMC9312038 DOI: 10.3390/biology11070973] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 06/23/2022] [Accepted: 06/27/2022] [Indexed: 12/18/2022]
Abstract
Immune-mediated inflammatory diseases (IMIDs) represent a large group of diseases (Crohn's, ulcerative colitis, psoriasis, lupus, and rheumatoid arthritis) evidenced by systemic inflammation and multiorgan involvement. IMIDs result in a reduced quality of life and an economic burden for individuals, health care systems, and countries. In this brief descriptive review, we will focus on some of the common biological pathways of these diseases from the point of view of psychoneuroimmunoendocrinology (PNIE). PNIE consists of four medical disciplines (psychology, nervous system, immune system, and endocrine system), which are key drivers behind the health-disease concept that a human being functions as a unit. We examine these drivers and emphasize the need for integrative treatments that addresses the disease from a psychosomatic point of view.
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Affiliation(s)
- Miguel A. Ortega
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcalá de Henares, Spain; (C.G.-M.); (O.F.-M.); (M.A.A.-M.); (A.M.G.-L.); (G.L.); (J.M.); (M.Á.-M.)
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Cielo García-Montero
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcalá de Henares, Spain; (C.G.-M.); (O.F.-M.); (M.A.A.-M.); (A.M.G.-L.); (G.L.); (J.M.); (M.Á.-M.)
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Oscar Fraile-Martinez
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcalá de Henares, Spain; (C.G.-M.); (O.F.-M.); (M.A.A.-M.); (A.M.G.-L.); (G.L.); (J.M.); (M.Á.-M.)
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Miguel Angel Alvarez-Mon
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcalá de Henares, Spain; (C.G.-M.); (O.F.-M.); (M.A.A.-M.); (A.M.G.-L.); (G.L.); (J.M.); (M.Á.-M.)
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
- Department of Psychiatry and Mental Health, Hospital Universitario Infanta Leonor, 28031 Madrid, Spain;
| | - Ana Maria Gómez-Lahoz
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcalá de Henares, Spain; (C.G.-M.); (O.F.-M.); (M.A.A.-M.); (A.M.G.-L.); (G.L.); (J.M.); (M.Á.-M.)
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Guillermo Lahera
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcalá de Henares, Spain; (C.G.-M.); (O.F.-M.); (M.A.A.-M.); (A.M.G.-L.); (G.L.); (J.M.); (M.Á.-M.)
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
- Psychiatry Service, Center for Biomedical Research in the Mental Health Network, University Hospital Príncipe de Asturias (CIBERSAM), 28806 Alcalá de Henares, Spain
| | - Jorge Monserrat
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcalá de Henares, Spain; (C.G.-M.); (O.F.-M.); (M.A.A.-M.); (A.M.G.-L.); (G.L.); (J.M.); (M.Á.-M.)
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Roberto Rodriguez-Jimenez
- Department of Legal Medicine and Psychiatry, Complutense University, 28040 Madrid, Spain;
- Institute for Health Research 12 de Octubre Hospital, (Imas 12)/CIBERSAM (Biomedical Research Networking Centre in Mental Health), 28041 Madrid, Spain
| | - Javier Quintero
- Department of Psychiatry and Mental Health, Hospital Universitario Infanta Leonor, 28031 Madrid, Spain;
- Department of Legal Medicine and Psychiatry, Complutense University, 28040 Madrid, Spain;
| | - Melchor Álvarez-Mon
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcalá de Henares, Spain; (C.G.-M.); (O.F.-M.); (M.A.A.-M.); (A.M.G.-L.); (G.L.); (J.M.); (M.Á.-M.)
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
- Immune System Diseases-Rheumatology, Oncology Service an Internal Medicine, University Hospital Príncipe de Asturias, (CIBEREHD), 28806 Alcalá de Henares, Spain
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Rodrigues BM, Mathias LS, Deprá IDC, Cury SS, de Oliveira M, Olimpio RMC, De Sibio MT, Gonçalves BM, Nogueira CR. Effects of Triiodothyronine on Human Osteoblast-Like Cells: Novel Insights From a Global Transcriptome Analysis. Front Cell Dev Biol 2022; 10:886136. [PMID: 35784485 PMCID: PMC9248766 DOI: 10.3389/fcell.2022.886136] [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: 02/28/2022] [Accepted: 05/06/2022] [Indexed: 11/13/2022] Open
Abstract
Background: Thyroid hormones play a significant role in bone development and maintenance, with triiodothyronine (T3) particularly being an important modulator of osteoblast differentiation, proliferation, and maintenance. However, details of the biological processes (BPs) and molecular pathways affected by T3 in osteoblasts remain unclear.Methods: To address this issue, primary cultures of human adipose-derived mesenchymal stem cells were subjected to our previously established osteoinduction protocol, and the resultant osteoblast-like cells were treated with 1 nm or 10 nm T3 for 72 h. RNA sequencing (RNA-Seq) was performed using the Illumina platform, and differentially expressed genes (DEGs) were identified from the raw data using Kallisto and DESeq2. Enrichment analysis of DEGs was performed against the Gene Ontology Consortium database for BP terms using the R package clusterProfiler and protein network analysis by STRING.Results: Approximately 16,300 genes were analyzed by RNA-Seq, with 343 DEGs regulated in the 1 nm T3 group and 467 upregulated in the 10 nm T3 group. Several independent BP terms related to bone metabolism were significantly enriched, with a number of genes shared among them (FGFR2, WNT5A, WNT3, ROR2, VEGFA, FBLN1, S1PR1, PRKCZ, TGFB3, and OSR1 for 1nM T3; and FZD1, SMAD6, NOG, NEO1, and ENG for 10 nm T3). An osteoblast-related search in the literature regarding this set of genes suggests that both T3 doses are unfavorable for osteoblast development, mainly hindering BMP and canonical and non-canonical WNT signaling.Conclusions: Therefore, this study provides new directions toward the elucidation of the mechanisms of T3 action on osteoblast metabolism, with potential future implications for the treatment of endocrine-related bone pathologies.
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Affiliation(s)
- Bruna Moretto Rodrigues
- Department of Internal Medicine, Medical School Botucatu, São Paulo State University (UNESP), Botucatu, Brazil
| | - Lucas Solla Mathias
- Department of Internal Medicine, Medical School Botucatu, São Paulo State University (UNESP), Botucatu, Brazil
| | - Igor de Carvalho Deprá
- Department of Internal Medicine, Medical School Botucatu, São Paulo State University (UNESP), Botucatu, Brazil
| | - Sarah Santiloni Cury
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, Brazil
| | - Miriane de Oliveira
- Department of Internal Medicine, Medical School Botucatu, São Paulo State University (UNESP), Botucatu, Brazil
| | | | - Maria Teresa De Sibio
- Department of Internal Medicine, Medical School Botucatu, São Paulo State University (UNESP), Botucatu, Brazil
| | - Bianca Mariani Gonçalves
- Department of Internal Medicine, Medical School Botucatu, São Paulo State University (UNESP), Botucatu, Brazil
| | - Célia Regina Nogueira
- Department of Internal Medicine, Medical School Botucatu, São Paulo State University (UNESP), Botucatu, Brazil
- *Correspondence: Célia Regina Nogueira,
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Lowin T, Kok C, Smutny S, Pongratz G. Impact of Δ 9-Tetrahydrocannabinol on Rheumatoid Arthritis Synovial Fibroblasts Alone and in Co-Culture with Peripheral Blood Mononuclear Cells. Biomedicines 2022; 10:1118. [PMID: 35625855 PMCID: PMC9138512 DOI: 10.3390/biomedicines10051118] [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: 04/08/2022] [Revised: 05/06/2022] [Accepted: 05/09/2022] [Indexed: 12/05/2022] Open
Abstract
δ9-Tetrahydrocannabinol (THC) has demonstrated anti-inflammatory effects in animal models of arthritis, but its mechanism of action and cellular targets are still unclear. The purpose of this study is to elucidate the effects of THC (0.1-25 µM) on synovial fibroblasts from patients with rheumatoid arthritis (RASF) and peripheral blood mononuclear cells (PBMC) from healthy donors in respect to proliferation, calcium mobilization, drug uptake, cytokine and immunoglobulin production. Intracellular calcium and drug uptake were determined by fluorescent dyes Cal-520 and PoPo3, respectively. Cytokine and immunoglobulin production were evaluated by ELISA. Cannabinoid receptors 1 and 2 (CB1 and CB2) were detected by flow cytometry. RASF express CB1 and CB2 and the latter was increased by tumor necrosis factor (TNF). In RASF, THC (≥5 µM) increased intracellular calcium levels/PoPo3 uptake in a TRPA1-dependent manner and reduced interleukin-8 (IL-8) and matrix metalloprotease 3 (MMP-3) production at high concentrations (25 µM). Proliferation was slightly enhanced at intermediate THC concentrations (1-10 µM) but was completely abrogated at 25 µM. In PBMC alone, THC decreased interleukin-10 (IL-10) production and increased immunoglobulin G (IgG). In PBMC/RASF co-culture, THC decreased TNF production when cells were stimulated with interferon-γ (IFN-γ) or CpG. THC provides pro- and anti-inflammatory effects in RASF and PBMC. This is dependent on the activating stimulus and concentration of THC. Therefore, THC might be used to treat inflammation in RA but it might need titrating to determine the effective concentration.
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Affiliation(s)
- Torsten Lowin
- Poliklinik, Funktionsbereich & Hiller Forschungszentrum für Rheumatologie, University Hospital Duesseldorf, 40225 Duesseldorf, Germany; (C.K.); (S.S.); (G.P.)
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Picca A, Calvani R, Marzetti E. Multisystem derangements in frailty and sarcopenia: a source for biomarker discovery. Curr Opin Clin Nutr Metab Care 2022; 25:173-177. [PMID: 35238804 DOI: 10.1097/mco.0000000000000828] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW Multisystem derangements, encompassing metabolic, musculoskeletal and stress-response systems, occur during aging and are associated with the development of physical frailty and sarcopenia. These modular changes are relevant sources for the identification of biomarkers for the two conditions. Here, we provide an up-to-date overview on existing biomarkers of physical frailty and sarcopenia and discuss emerging approaches for biomarker discovery. RECENT FINDINGS Inflammatory, metabolic and hematologic markers are shared between physical frailty and sarcopenia. Gut microbial derivatives and damage-associated molecular patterns transferred via extracellular vesicles have been indicated as possible gut-muscle axis regulators and candidate markers of physical frailty and sarcopenia. SUMMARY Mediators of metabolic, musculoskeletal and stress-response system dysregulation are shared by physical frailty and sarcopenia and indicate the existence of common pathophysiological pathways. Multiplatform biomarker analyses have been proposed as an innovating approach for tracking the multifaceted and dynamic nature of physical frailty and sarcopenia. Upon validation, the identified biomarkers may support diagnostic makeup and tracking of the two conditions in both research and clinical settings.
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Affiliation(s)
- Anna Picca
- Fondazione Policlinico Universitario 'Agostino Gemelli' IRCCS
| | | | - Emanuele Marzetti
- Fondazione Policlinico Universitario 'Agostino Gemelli' IRCCS
- Università Cattolica del Sacro Cuore, Department of Geriatrics and Orthopedics, Rome, Italy
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Arora P, Singh K, Kumari M, Trivedi R. Temporal profile of serum metabolites and inflammation following closed head injury in rats is associated with HPA axis hyperactivity. Metabolomics 2022; 18:28. [PMID: 35486220 DOI: 10.1007/s11306-022-01886-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 04/06/2022] [Indexed: 10/18/2022]
Abstract
INTRODUCTION Closed head injury (CHI) causes neurological disability along with systemic alterations that can activate neuro-endocrine response through hypothalamic-pituitary-adrenal (HPA) axis activation. A dysregulated HPA axis function can lead to relocation of energy substrates and alteration in metabolic pathways and inflammation at the systemic level. OBJECTIVES Assessment of time-dependent changes in serum metabolites and inflammation after both mild and moderate CHI. Along with this, serum corticosterone levels and hypothalamic microglial response were observed. METHODS Rats underwent mild and moderate weight-drop injury and their serum and hypothalamus were assessed at acute, sub-acute and chronic timepoints. Changes in serum metabolomics were determined using high resolution NMR spectroscopy. Serum inflammatory cytokine, corticosterone levels and hypothalamic microglia were assessed at all timepoints. RESULTS Metabolites including lactate, choline and branched chain amino acids were found as the classifiers that helped distinguish between control and injured rats during acute, sub-acute and chronic timepoints. While, increased αglucose: βglucose and TMAO: choline ratios after acute and sub-acute timepoints of mild injury differentiated from moderate injured rats. The injured rats also showed distinct inflammatory profile where IL-1β and TNF-α levels were upregulated in moderate injured rats while IL-10 levels were downregulated in mild injured rats. Furthermore, injury specific alterations in serum metabolic and immunologic profile were found to be associated with hyperactive HPA axis, with consistent increase in serum corticosterone concentration post injury. The hypothalamic microglia showed a characteristic activated de-ramified cellular morphology in both mild and moderate injured rats. CONCLUSION The study suggests that HPA axis hyperactivity along with hypothalamic microglial activation led to temporal changes in the systemic metabolism and inflammation. These time dependent changes in the metabolite profile of rats can further strengthen the knowledge of diagnostic markers and help distinguish injury related outcomes after TBI.
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Affiliation(s)
- Palkin Arora
- Radiological, Nuclear and Imaging Sciences (RNAIS), Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, Delhi, 110054, India
- Department of Biochemistry, Panjab University, Chandigarh, 160014, India
| | - Kavita Singh
- Radiological, Nuclear and Imaging Sciences (RNAIS), Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, Delhi, 110054, India
- Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Megha Kumari
- Radiological, Nuclear and Imaging Sciences (RNAIS), Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, Delhi, 110054, India
- Department of Biotechnology, Delhi Technological University (DTU), Delhi, 110042, India
| | - Richa Trivedi
- Radiological, Nuclear and Imaging Sciences (RNAIS), Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, Delhi, 110054, India.
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Ohlsson C, Langenskiöld M, Smidfelt K, Poutanen M, Ryberg H, Norlén AK, Nordanstig J, Bergström G, Tivesten Å. Low Progesterone and Low Estradiol Levels Associate With Abdominal Aortic Aneurysms in Men. J Clin Endocrinol Metab 2022; 107:e1413-e1425. [PMID: 34865072 PMCID: PMC8947245 DOI: 10.1210/clinem/dgab867] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Indexed: 11/26/2022]
Abstract
CONTEXT Male sex is a major risk factor for abdominal aortic aneurysms (AAA) but few studies have addressed associations between sex hormone levels and AAA. OBJECTIVE We aimed to describe the associations between serum sex steroids and early, screening-detected AAA in men. METHODS We validated a high-sensitivity liquid chromatography-tandem mass spectrometry assay for comprehensive serum sex hormone profiling. This assay was then employed in a case-control study including 147 men with AAA (infrarenal aorta ≥ 30 mm) and 251 AAA-free controls recruited at the general population-based ultrasound screening for AAA in 65-year-old Swedish men. OUTCOMES INCLUDED associations between dehydroepiandrosterone, progesterone, 17α-hydroxyprogesterone, androstenedione, estrone, testosterone, dihydrotestosterone, and estradiol and AAA presence. RESULTS Dehydroepiandrosterone, progesterone, 17α-hydroxyprogesterone, testosterone, and estradiol, but not the other hormones, were lower in men with AAA. In models with adjustments for known AAA risk factors and comorbidity, only progesterone (odds ratio per SD decrease 1.62 [95% CI, 1.18-2.22]) and estradiol (1.40 [95% CI, 1.04-1.87]) remained inversely associated with the presence of AAA. Progesterone and estradiol contributed with independent additive information for prediction of AAA presence; compared with men with high (above median) levels, men with low (below median) levels of both hormones had a 4-fold increased odds ratio for AAA (4.06 [95% CI, 2.25-7.31]). CONCLUSION Measured by a high-performance sex steroid assay, progesterone and estradiol are inversely associated with AAA in men, independent of known risk factors. Future studies should explore whether progesterone and estradiol, which are important reproductive hormones in women, are protective in human AAA.
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Affiliation(s)
- Claes Ohlsson
- Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden
- Department of Drug Treatment, Sahlgrenska University Hospital, Region Västra Götaland, SE-413 45 Gothenburg, Sweden
| | - Marcus Langenskiöld
- The Vascular Surgery Research Group, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden
| | - Kristian Smidfelt
- The Vascular Surgery Research Group, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden
| | - Matti Poutanen
- Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden
- Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, 20520 Turku, Finland
| | - Henrik Ryberg
- Department of Clinical Chemistry, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden
| | - Anna-Karin Norlén
- Department of Clinical Chemistry, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden
| | - Joakim Nordanstig
- The Vascular Surgery Research Group, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden
| | - Göran Bergström
- Wallenberg Laboratory for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden
- Department of Clinical Physiology, Sahlgrenska University Hospital, Region Västra Götaland, SE-413 45 Gothenburg, Sweden
| | - Åsa Tivesten
- Wallenberg Laboratory for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden
- Department of Endocrinology, Sahlgrenska University Hospital, Region Västra Götaland, SE-413 45 Gothenburg, Sweden
- Correspondence: Åsa Tivesten, MD, PhD, Wallenberg Laboratory for Cardiovascular and Metabolic Research, Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Gothenburg, Sweden.
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Aghajani M, Rahmati-Ahmadabad S, Zamani F, Ghanbari B, Azarbayjani MA. The effects of high-intensity interval training and orlistat on selected adipokines and cytokines in obese women. GERMAN JOURNAL OF EXERCISE AND SPORT RESEARCH 2022; 52:87-96. [DOI: 10.1007/s12662-021-00749-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 08/15/2021] [Indexed: 10/20/2022]
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The role of plasminogen activator inhibitor-1 in gynecological and obstetrical diseases: an update review. J Reprod Immunol 2022; 150:103490. [DOI: 10.1016/j.jri.2022.103490] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 01/20/2022] [Accepted: 01/25/2022] [Indexed: 11/21/2022]
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Kozera EK, Lowes MA, Hsiao JL, Frew JW. Clinical considerations in the management of hidradenitis suppurativa in women. Int J Womens Dermatol 2021; 7:664-671. [PMID: 35028361 PMCID: PMC8714605 DOI: 10.1016/j.ijwd.2021.10.012] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 10/20/2021] [Accepted: 10/24/2021] [Indexed: 12/20/2022] Open
Abstract
Hidradenitis suppurativa (HS) is a chronic, inflammatory disease of the skin with a predilection for women. The role of sex hormones, including estrogen and progesterone, is incompletely understood, but alterations in hormone levels may play a role in disease activity for many patients. Specific clinical considerations should be made for women with HS, particularly in the setting of pregnancy, childbirth, breastfeeding, and menopause. Current knowledge gaps regarding HS include the cumulative impact of disease across an individual's lifespan, as well as the mechanistic role of sex hormones in the disease. An improved understanding of the pathophysiologic role of hormones in HS would optimize our ability to use targeted therapies for hormonally driven disease. Psychological and psychosexual support for women with HS is an important facet of any holistic management strategy for the disease. This article integrates up-to-date pathogenic and mechanistic insights with evidence-based clinical management to optimize care for women with HS.
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Affiliation(s)
- Emily K. Kozera
- Liverpool Hospital Department of Dermatology, Sydney, Australia
| | | | - Jennifer L. Hsiao
- Division of Dermatology, University of California, Los Angeles, California
| | - John W. Frew
- Liverpool Hospital Department of Dermatology, Sydney, Australia
- University of New South Wales, Sydney, Australia
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Mohammadi H, Talebi S, Ghavami A, Rafiei M, Sharifi S, Faghihimani Z, Ranjbar G, Miraghajani M, Askari G. Effects of zinc supplementation on inflammatory biomarkers and oxidative stress in adults: A systematic review and meta-analysis of randomized controlled trials. J Trace Elem Med Biol 2021; 68:126857. [PMID: 34560424 DOI: 10.1016/j.jtemb.2021.126857] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 09/03/2021] [Accepted: 09/10/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND & OBJECTIVE Current evidence is debatable regarding the feasible effects of zinc supplementation on the inflammation and oxidative stress status of adults. This systematic review and meta-analysis aimed to clarify this inconclusiveness. MATERIALS AND METHODS Literature search was conducted via online databases such as PubMed, Scopus, ISI Web of Science, Cochrane Library, and Google Scholar until June 2020. The overall effect was presented as the weighted mean difference (WMD) at 95 % confidence interval (CI) in a random-effects meta-analysis model. Publication bias was also assessed using Egger's and Begg's statistics. RESULTS In total, 25 clinical trials (n = 1428) were reviewed, which indicated that zinc supplementation significantly affects the concentration of C- reactive protein (WMD: -0.03 mg/l; 95 % CI: -0.06, 0.0; P = 0.029), interlukin-6 (WMD: -3.81 pg/mL; 95 % CI: -6.87, -0.76; P = 0.014), malondialdehyde (WMD: -0.78 μmol/l; 95 % CI: -1.14, -0.42; P < 0.001), and total antioxidant capacity (WMD: 95.96 mmol/l; 95 % CI: 22.47, 169.44; P = 0.010). In addition, a significant between-study heterogeneity and a non-significant increment was reported in nitric oxide (WMD: 1.47 μmol/l; 95 % CI: -2.45, 5.40; P = 0.461) and glutathione (WMD: 34.84 μmol/l; 95 % CI: -5.12, 74.80; P = 0.087). CONCLUSION According to the results, zinc supplementation may have beneficial anti-inflammatory and anti-oxidative effects in adults.
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Affiliation(s)
- Hamed Mohammadi
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Sepide Talebi
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Abed Ghavami
- Student Research Committee, Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Masoumeh Rafiei
- Student Research Committee, Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Shima Sharifi
- Student Research Committee, Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Zahra Faghihimani
- Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Golnaz Ranjbar
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maryam Miraghajani
- Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; The Early Life Research Unit, Division of Child Health, Obstetrics and Gynecology, and Nottingham Digestive Disease Centre and Biomedical Research Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Gholamreza Askari
- Department of Community Nutrition, School of Nutrition and Food Sciences, Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
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35
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Belcher T, Dubois V, Rivera-Millot A, Locht C, Jacob-Dubuisson F. Pathogenicity and virulence of Bordetella pertussis and its adaptation to its strictly human host. Virulence 2021; 12:2608-2632. [PMID: 34590541 PMCID: PMC8489951 DOI: 10.1080/21505594.2021.1980987] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
The highly contagious whooping cough agent Bordetella pertussis has evolved as a human-restricted pathogen from a progenitor which also gave rise to Bordetella parapertussis and Bordetella bronchiseptica. While the latter colonizes a broad range of mammals and is able to survive in the environment, B. pertussis has lost its ability to survive outside its host through massive genome decay. Instead, it has become a highly successful human pathogen by the acquisition of tightly regulated virulence factors and evolutionary adaptation of its metabolism to its particular niche. By the deployment of an arsenal of highly sophisticated virulence factors it overcomes many of the innate immune defenses. It also interferes with vaccine-induced adaptive immunity by various mechanisms. Here, we review data from invitro, human and animal models to illustrate the mechanisms of adaptation to the human respiratory tract and provide evidence of ongoing evolutionary adaptation as a highly successful human pathogen.
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Affiliation(s)
- Thomas Belcher
- Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, Lille, France
| | - Violaine Dubois
- Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, Lille, France
| | - Alex Rivera-Millot
- Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, Lille, France
| | - Camille Locht
- Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, Lille, France
| | - Françoise Jacob-Dubuisson
- Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, Lille, France
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36
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Gorabi AM, Abbasifard M, Imani D, Aslani S, Razi B, Alizadeh S, Bagheri-Hosseinabadi Z, Sathyapalan T, Sahebkar A. Effect of curcumin on C-reactive protein as a biomarker of systemic inflammation: An updated meta-analysis of randomized controlled trials. Phytother Res 2021; 36:85-97. [PMID: 34586711 DOI: 10.1002/ptr.7284] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 06/27/2021] [Accepted: 08/06/2021] [Indexed: 11/11/2022]
Abstract
It has been suggested that curcumin is a potential agent for lowering the levels of C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP), as markers of inflammation. In the current meta-analysis, we attempted to clarify the efficacy of curcumin supplementation in lowering the concentrations of CRP and hs-CRP in patients with autoinflammatory conditions. Nine studies were found evaluating the effect of curcumin on CRP levels, while 23 studies were identified for hs-CRP. CRP concentration was decreased significantly compared to the placebo (WMD = -3.67 mg/L, 95% CI = -6.96 to -0.38, p = 0.02). There was a significant effect of curcumin at dose ≤1,000 mg/day on the CRP concentration. CRP concentration significantly decreased after >10-week intervention compared with placebo.hs-CRP concentration in the intervention group was significantly lower than that of placebo group. A significant effect of curcumin consumption was detected on the serum level of hs-CRP in studies with prescribing ≤1,000 mg/day, and those with ≤10-week duration of intervention. Curcumin consumption resulted in a reduction of hs-CRP in a non-linear fashion with stronger effects with less than 2000 mg curcumin per day. Curcumin seems to be beneficial in decreasing the hs-CRP and CRP levels in proinflammatory settings.
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Affiliation(s)
- Armita Mahdavi Gorabi
- Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mitra Abbasifard
- Department of Internal Medicine, Ali-Ibn Abi-Talib hospital, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.,Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan, Iran
| | - Danyal Imani
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Saeed Aslani
- Department of Immunology, School of medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Bahman Razi
- Department of Hematology and Blood transfusion, School of Medicine, Tarbiat Modares University, Tehran, Iran
| | - Shahab Alizadeh
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Bagheri-Hosseinabadi
- Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan, Iran.,Department of Clinical Biochemistry, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Thozhukat Sathyapalan
- Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, United Kingdom
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,School of Medicine, The University of Western Australia, Perth, Australia.,School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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Gorabi AM, Aslani S, Imani D, Razi B, Sathyapalan T, Sahebkar A. Effect of resveratrol on C-reactive protein: An updated meta-analysis of randomized controlled trials. Phytother Res 2021; 35:6754-6767. [PMID: 34472150 DOI: 10.1002/ptr.7262] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 06/27/2021] [Accepted: 08/14/2021] [Indexed: 12/13/2022]
Abstract
We conducted a meta-analysis on the available randomized clinical trials (RCTs) to assess the role of resveratrol in lowering C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) levels, as markers of inflammation, in various inflammatory disorders. Literature search through Medline/PubMed, Scopus, ISI Web of Science, and Cochrane Library yielded 35 RCTs (24 studies for hs-CRP and 11 studies for CRP). Pooled results revealed that resveratrol supplementation significantly reduced the hs-CRP (MWD = -0.40 mg/L; 95% CI: -0.70 to -0.09 mg/L; p = .01) and CRP (MWD = -0.31 mg/L; 95% CI: -0.47 to -0.15 mg/L; p < .001) levels in serum. Subgroup analysis revealed that resveratrol in group with ≥10 weeks significantly reduces hs-CRP levels (MWD = -0.48 mg/L; 95% CI: -0.92 to -0.04 mg/L; p = .03) and CRP (WMD = -0.47 mg/L, 95% CI = -0.69 to -0.25, p < .001). A dose of ≥500 mg/day supplementation improves the levels of CRP, but not hs-CRP. This meta-analysis demonstrates that resveratrol consumption is effective in lowering the levels of CRP and hs-CRP in inflammatory conditions, especially if supplementation takes place for ≥10 weeks with ≥500 mg/day.
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Affiliation(s)
- Armita Mahdavi Gorabi
- Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Saeed Aslani
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Danyal Imani
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Bahman Razi
- Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Thozhukat Sathyapalan
- Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull, UK
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,School of Medicine, The University of Western Australia, Perth, Australia.,School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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38
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Martín AI, Priego T, Moreno-Ruperez Á, González-Hedström D, Granado M, López-Calderón A. IGF-1 and IGFBP-3 in Inflammatory Cachexia. Int J Mol Sci 2021; 22:ijms22179469. [PMID: 34502376 PMCID: PMC8430490 DOI: 10.3390/ijms22179469] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Revised: 08/05/2021] [Accepted: 08/28/2021] [Indexed: 02/04/2023] Open
Abstract
Inflammation induces a wide response of the neuroendocrine system, which leads to modifications in all the endocrine axes. The hypothalamic–growth hormone (GH)–insulin-like growth factor-1 (IGF-1) axis is deeply affected by inflammation, its response being characterized by GH resistance and a decrease in circulating levels of IGF-1. The endocrine and metabolic responses to inflammation allow the organism to survive. However, in chronic inflammatory conditions, the inhibition of the hypothalamic–GH–IGF-1 axis contributes to the catabolic process, with skeletal muscle atrophy and cachexia. Here, we review the changes in pituitary GH secretion, IGF-1, and IGF-1 binding protein-3 (IGFBP-3), as well as the mechanism that mediated those responses. The contribution of GH and IGF-1 to muscle wasting during inflammation has also been analyzed.
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Affiliation(s)
- Ana Isabel Martín
- Department of Physiology, Faculty of Medicine, Complutense University of Madrid, 28040 Madrid, Spain; (A.I.M.); (Á.M.-R.)
| | - Teresa Priego
- Department of Physiology, Faculty of Nursing, Physiotherapy and Podiatry, Complutense University of Madrid, 28040 Madrid, Spain;
| | - Álvaro Moreno-Ruperez
- Department of Physiology, Faculty of Medicine, Complutense University of Madrid, 28040 Madrid, Spain; (A.I.M.); (Á.M.-R.)
| | - Daniel González-Hedström
- Department of Physiology, Faculty of Medicine, Autonomous University of Madrid, 28049 Madrid, Spain; (D.G.-H.); (M.G.)
- Pharmactive Biotech Products S.L. Parque Científico de Madrid, Avenida del Doctor Severo Ochoa, 37 Local 4J, 28108 Alcobendas, Spain
| | - Miriam Granado
- Department of Physiology, Faculty of Medicine, Autonomous University of Madrid, 28049 Madrid, Spain; (D.G.-H.); (M.G.)
- CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Asunción López-Calderón
- Department of Physiology, Faculty of Medicine, Complutense University of Madrid, 28040 Madrid, Spain; (A.I.M.); (Á.M.-R.)
- Correspondence: ; Tel.: +34-913-941-491
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Gaspari L, Paris F, Kalfa N, Soyer-Gobillard MO, Sultan C, Hamamah S. Experimental Evidence of 2,3,7,8-Tetrachlordibenzo-p-Dioxin (TCDD) Transgenerational Effects on Reproductive Health. Int J Mol Sci 2021; 22:ijms22169091. [PMID: 34445797 PMCID: PMC8396488 DOI: 10.3390/ijms22169091] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 08/09/2021] [Accepted: 08/19/2021] [Indexed: 12/12/2022] Open
Abstract
Previous studies have demonstrated that endocrine disruptors (EDs) can promote the transgenerational inheritance of disease susceptibility. Among the many existing EDs, 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) affects reproductive health, including in humans, following direct occupational exposure or environmental disasters, for instance the Agent Orange sprayed during the Vietnam War. Conversely, few studies have focused on TCDD multigenerational and transgenerational effects on human reproductive health, despite the high amount of evidence in animal models of such effects on male and female reproductive health that mimic human reproductive system disorders. Importantly, these studies show that paternal ancestral TCDD exposure substantially contributes to pregnancy outcome and fetal health, although pregnancy outcome is considered tightly related to the woman’s health. In this work, we conducted a systematic review of the literature and a knowledge synthesis in order (i) to describe the findings obtained in rodent models concerning TCDD transgenerational effects on reproductive health and (ii) to discuss the epigenetic molecular alterations that might be involved in this process. As ancestral toxicant exposure cannot be changed in humans, identifying the crucial reproductive functions that are negatively affected by such exposure may help clinicians to preserve male and female fertility and to avoid adverse pregnancy outcomes.
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Affiliation(s)
- Laura Gaspari
- Unité d’Endocrinologie-Gynécologie Pédiatrique, Service de Pédiatrie, CHU Montpellier, University of Montpellier, 34090 Montpellier, France; (L.G.); (F.P.); (C.S.)
- Centre de Référence Maladies Rares du Développement Génital, Constitutif Sud, CHU Montpellier, University of Montpellier, Hôpital Lapeyronie, 34090 Montpellier, France;
- INSERM 1203, Développement Embryonnaire Fertilité Environnement, University of Montpellier, 34295 Montpellier, France
| | - Françoise Paris
- Unité d’Endocrinologie-Gynécologie Pédiatrique, Service de Pédiatrie, CHU Montpellier, University of Montpellier, 34090 Montpellier, France; (L.G.); (F.P.); (C.S.)
- Centre de Référence Maladies Rares du Développement Génital, Constitutif Sud, CHU Montpellier, University of Montpellier, Hôpital Lapeyronie, 34090 Montpellier, France;
- INSERM 1203, Développement Embryonnaire Fertilité Environnement, University of Montpellier, 34295 Montpellier, France
| | - Nicolas Kalfa
- Centre de Référence Maladies Rares du Développement Génital, Constitutif Sud, CHU Montpellier, University of Montpellier, Hôpital Lapeyronie, 34090 Montpellier, France;
- Département de Chirurgie Viscérale et Urologique Pédiatrique, CHU Montpellier, University of Montpellier, Hôpital Lapeyronie, 34090 Montpellier, France
- Institut Debrest de Santé Publique IDESP, UMR INSERM, University of Montpellier, 34090 Montpellier, France
| | - Marie-Odile Soyer-Gobillard
- CNRS, Sorbonne University, 75006 Paris, France;
- Association Hhorages-France, 95270 Asnières-sur-Oise, France
| | - Charles Sultan
- Unité d’Endocrinologie-Gynécologie Pédiatrique, Service de Pédiatrie, CHU Montpellier, University of Montpellier, 34090 Montpellier, France; (L.G.); (F.P.); (C.S.)
| | - Samir Hamamah
- INSERM 1203, Développement Embryonnaire Fertilité Environnement, University of Montpellier, 34295 Montpellier, France
- Département de Biologie de la Reproduction, Biologie de la Reproduction/DPI et CECOS, CHU Montpellier, University of Montpellier, 34090 Montpellier, France
- Correspondence: ; Fax: +33-4-67-33-62-90
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40
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Alam MA, Quamri MA, Haider N. Efficacy and safety of Barg-e-Sahajna ( Moringa oleifera Lam.) in primary hypothyroidism. Drug Metab Pers Ther 2021; 37:21-26. [PMID: 34449175 DOI: 10.1515/dmpt-2021-0136] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 06/28/2021] [Indexed: 11/15/2022]
Abstract
OBJECTIVES Hypothyroidism is the most common disorder arising from hormone deficiency. It frequently affects women than men. The prevalence of overall hypothyroidism has been reported to be 4.8-11%. Levothyroxine is the treatment of choice for all types of hypothyroidism. The purpose of this pilot study was to evaluate the efficacy and safety of Barg-e-Sahajna (Leaves of Moringa oleifera Lam.) among diagnosed patients of primary hypothyroidism. METHODS This study was an open observational study. A total of 22 patients were screened, out of which 10 were excluded (did not meet inclusion criteria) and 2 refused to consent to be part of the study, rest 10 participants were enrolled after obtaining written informed consent finally 8 subjects completed the study and 2 are dropout in last follow up. The drug was given in the form of decoction at the dose of 5 g fresh leaves twice a day after meal for 45 days. RESULTS The study effects on objective parameter thyroid stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) were found extremely significant when compared before (16.62 ± 11.49, 132 ± 19.32, 9.28 ± 1.46) and after (4.75 ± 3.12, 150.37 ± 20.68, 11.84 ± 3.81) treatment with a significant decrease in serum TSH level (p<0.0246) and an increase in serum T3 (p<0.0005) and T4 (p<0.0438) levels. The results were analyzed using paired "t" test. CONCLUSIONS The improvements in thyroid profiles (TSH, T3 and T4) after consuming 'Barg-e-Sahajna' show that the test drug is effective in primary hypothyroidism and the relief was considerable. No significant effect on safety parameters (serum-glutamic-oxaloacetic-transaminase [SGOT], serum glutamic-pyruvic transaminase [SGPT], blood urea, and serum creatinine) was observed. Therefore, it may be concluded that the Barg-e-Sahajna is preliminarily safe and effective in the management of primary hypothyroidism.
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Affiliation(s)
- Md Anzar Alam
- Department of Moalajat (Medicine), National Institute of Unani Medicine (Under Ministry of AYUSH), Bangalore, India
| | - Mohd Aleemuddin Quamri
- Department of Moalajat (Medicine), National Institute of Unani Medicine (Under Ministry of AYUSH), Bangalore, India
| | - Nafis Haider
- Department of Basic Medical Sciences Unit, Prince Sultan Military College of Health Sciences, Dhahran, Kingdom of Saudi Arabia
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Alam MA, Quamri MA, Haider N. Efficacy and safety of Barg-e-Sahajna ( Moringa olifera Lam.) in primary hypothyroidism. Drug Metab Pers Ther 2021; 0:dmdi-2021-0136. [PMID: 34390640 DOI: 10.1515/dmdi-2021-0136] [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: 04/29/2021] [Accepted: 06/28/2021] [Indexed: 11/15/2022]
Abstract
OBJECTIVES Hypothyroidism is the most common disorder arising from hormone deficiency. It frequently affects women than men. The prevalence of overall hypothyroidism has been reported to be 4.8-11%. Levothyroxine is the treatment of choice for all types of hypothyroidism. The purpose of this pilot study was to evaluate the efficacy and safety of Barg-e-Sahajna (Leaves of Moringa olifera Lam.) among diagnosed patients of primary hypothyroidism. METHODS This study was an open observational study. A total of 22 patients were screened, out of which 10 were excluded (did not meet inclusion criteria) and 2 refused to consent to be part of the study, rest 10 participants were enrolled after obtaining written informed consent finally 8 subjects completed the study and 2 are dropout in last follow up. The drug was given in the form of decoction at the dose of 5 g fresh leaves twice a day after meal for 45 days. RESULTS The study effects on objective parameter thyroid stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) were found extremely significant when compared before (16.62 ± 11.49, 132 ± 19.32, 9.28 ± 1.46) and after (4.75 ± 3.12, 150.37 ± 20.68, 11.84 ± 3.81) treatment with a significant decrease in serum TSH level (p<0.0246) and an increase in serum T3 (p<0.0005) and T4 (p<0.0438) levels. The results were analyzed using paired "t" test. CONCLUSIONS The improvements in thyroid profiles (TSH, T3 and T4) after consuming 'Barg-e-Sahajna' show that the test drug is effective in primary hypothyroidism and the relief was considerable. No significant effect on safety parameters (serum-glutamic-oxaloacetic-transaminase [SGOT], serum glutamic-pyruvic transaminase [SGPT], blood urea, and serum creatinine) was observed. Therefore, it may be concluded that the Barg-e-Sahajna is preliminarily safe and effective in the management of primary hypothyroidism.
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Affiliation(s)
- Md Anzar Alam
- Department of Moalajat (Medicine), National Institute of Unani Medicine (Under Ministry of AYUSH), Bangalore, India
| | - Mohd Aleemuddin Quamri
- Department of Moalajat (Medicine), National Institute of Unani Medicine (Under Ministry of AYUSH), Bangalore, India
| | - Nafis Haider
- Department of Basic Medical Sciences Unit, Prince Sultan Military College of Health Sciences, Dhahran, Kingdom of Saudi Arabia
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Dinsdale NL, Crespi BJ. Endometriosis and polycystic ovary syndrome are diametric disorders. Evol Appl 2021; 14:1693-1715. [PMID: 34295358 PMCID: PMC8288001 DOI: 10.1111/eva.13244] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 04/09/2021] [Accepted: 04/10/2021] [Indexed: 12/15/2022] Open
Abstract
Evolutionary and comparative approaches can yield novel insights into human adaptation and disease. Endometriosis and polycystic ovary syndrome (PCOS) each affect up to 10% of women and significantly reduce the health, fertility, and quality of life of those affected. PCOS and endometriosis have yet to be considered as related to one another, although both conditions involve alterations to prenatal testosterone levels and atypical functioning of the hypothalamic-pituitary-gonadal (HPG) axis. Here, we propose and evaluate the novel hypothesis that endometriosis and PCOS represent extreme and diametric (opposite) outcomes of variation in HPG axis development and activity, with endometriosis mediated in notable part by low prenatal and postnatal testosterone, while PCOS is mediated by high prenatal testosterone. This diametric disorder hypothesis predicts that, for characteristics shaped by the HPG axis, including hormonal profiles, reproductive physiology, life-history traits, and body morphology, women with PCOS and women with endometriosis will manifest opposite phenotypes. To evaluate these predictions, we review and synthesize existing evidence from developmental biology, endocrinology, physiology, life history, and epidemiology. The hypothesis of diametric phenotypes between endometriosis and PCOS is strongly supported across these diverse fields of research. Furthermore, the contrasts between endometriosis and PCOS in humans parallel differences among nonhuman animals in effects of low versus high prenatal testosterone on female reproductive traits. These findings suggest that PCOS and endometriosis represent maladaptive extremes of both female life-history variation and expression of sexually dimorphic female reproductive traits. The diametric disorder hypothesis for endometriosis and PCOS provides novel, unifying, proximate, and evolutionary explanations for endometriosis risk, synthesizes diverse lines of research concerning the two most common female reproductive disorders, and generates future avenues of research for improving the quality of life and health of women.
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Affiliation(s)
| | - Bernard J. Crespi
- Department of Biological SciencesSimon Fraser UniversityBurnabyBCCanada
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Gorabi AM, Razi B, Aslani S, Abbasifard M, Imani D, Sathyapalan T, Sahebkar A. Effect of curcumin on proinflammatory cytokines: A meta-analysis of randomized controlled trials. Cytokine 2021; 143:155541. [PMID: 33934954 DOI: 10.1016/j.cyto.2021.155541] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 03/27/2021] [Accepted: 04/09/2021] [Indexed: 12/23/2022]
Abstract
It has been suggested that curcumin has the potential for lowering inflammation. In the current meta-analysis, we attempted to clarify the efficacy of curcumin/turmeric supplementation in reducing concentrations of interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-α in patients with an inflammatory background. The main databases were searched to identify eligible trials evaluating the effect of curcumin in reducing IL-1, IL-6, IL-8, and TNF-α in serum up to March 2021. The effect sizes for weighted mean difference (WMD) and 95% confidence intervals (CI) were calculated. Overall, 32 randomized controlled trials (RCTs) were included. There was a significant decrease in the serum levels of IL-1 (WMD = -2.33 pg/ml, 95% CI = -3.33 to -1.34, P < 0.001) and TNF-α (WMD = -1.61 pg/ml, 95% CI = -2.72, -0.51, P < 0.001) compared to the placebo group following treatment. Nonetheless, curcumin/turmeric supplementation was non-significantly associated with reduced levels of IL-6 (WMD = -0.33 pg/ml, 95% CI = -0.99-0.34, P = 0.33) and increased levels of IL-8 (WMD = 0.52 pg/ml, 95% CI = -1.13-2.17, P = 0.53). The dose-responses analysis indicated that curcumin/turmeric supplementation resulted in IL-1 and IL-8 alteration in a non-linear model. Subgroup analysis according to duration and dose of treatment and target population revealed diverse outcomes. Curcumin could have a beneficial effect in reducing the proinflammatory cytokines IL-1 and TNF-α, but not IL-6 and IL-8 levels.
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Affiliation(s)
- Armita Mahdavi Gorabi
- Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Bahman Razi
- Department of Hematology and Blood Transfusion, School of Medicine, Tarbiat Modares University, Tehran, Iran
| | - Saeed Aslani
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mitra Abbasifard
- Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Department of Internal Medicine, School of Medicine, Ali Ibn Abi Talib Hospital, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Danyal Imani
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Thozhukat Sathyapalan
- Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull, United Kingdom
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
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Lopes PC, French SS, Woodhams DC, Binning SA. Sickness behaviors across vertebrate taxa: proximate and ultimate mechanisms. J Exp Biol 2021; 224:260576. [PMID: 33942101 DOI: 10.1242/jeb.225847] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
There is nothing like a pandemic to get the world thinking about how infectious diseases affect individual behavior. In this respect, sick animals can behave in ways that are dramatically different from healthy animals: altered social interactions and changes to patterns of eating and drinking are all hallmarks of sickness. As a result, behavioral changes associated with inflammatory responses (i.e. sickness behaviors) have important implications for disease spread by affecting contacts with others and with common resources, including water and/or sleeping sites. In this Review, we summarize the behavioral modifications, including changes to thermoregulatory behaviors, known to occur in vertebrates during infection, with an emphasis on non-mammalian taxa, which have historically received less attention. We then outline and discuss our current understanding of the changes in physiology associated with the production of these behaviors and highlight areas where more research is needed, including an exploration of individual and sex differences in the acute phase response and a greater understanding of the ecophysiological implications of sickness behaviors for disease at the population level.
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Affiliation(s)
- Patricia C Lopes
- Schmid College of Science and Technology, Chapman University, Orange, CA 92866, USA
| | - Susannah S French
- Department of Biology and The Ecology Center, Utah State University, Logan, UT 84322, USA
| | - Douglas C Woodhams
- Department of Biology, University of Massachusetts Boston, Boston, MA 02125, USA
| | - Sandra A Binning
- Département de Sciences Biologiques, Université de Montréal, Montréal, QC, Canada, H3C 3J7
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Xu T, Wu X, Lu X, Liang Y, Mao Y, Loor JJ, Yang Z. Metformin activated AMPK signaling contributes to the alleviation of LPS-induced inflammatory responses in bovine mammary epithelial cells. BMC Vet Res 2021; 17:97. [PMID: 33648513 PMCID: PMC7923493 DOI: 10.1186/s12917-021-02797-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 02/02/2021] [Indexed: 12/15/2022] Open
Abstract
Background Lipopolysaccharides (LPS) derived from gram-negative bacterial are often regarded as primary inducer of bovine mammary inflammation. This study evaluated the biological response of metformin activated AMPK signaling on LPS-induced inflammatory responses and metabolic changes in primary bovine mammary epithelial cells (pbMEC). The pbMEC were exposed to either 3 mmol/L Metf. for 12 h as Metf. group (Metf.) or 2 μg/mL LPS for 6 h as LPS group (LPS). Cells pretreated with 3 mmol/L metformin for 12 h followed by washing and 2 μg/mL LPS exposure for 6 h were served as ML group (ML). PBS was added to cells as the control group (Con.). Results Pre-incubation with Metf. inhibited LPS-induced expression of pro-inflammatory genes (TNF, IL1B, IL6, CXCL8, MYD88 and TLR4) and proteins (IL-1β, TNF-α, NLRP3, Caspase1, ASC) and was accompanied by increased activation of AMPK signaling. Compared with the LPS group, phosphorylation of p65 and IκBα in the ML group were decreased and accumulation of NF-κB in the nucleus was significantly reduced by pretreatment with metformin. Metformin protects the cells from the increase of LPS-induced binding activity of NF-κB on both TNFA and IL1B promoters. Compared with the LPS group, genes (G6PC, PCK2) and proteins (SREBP1, SCD1) related to lipogenesis and carbohydrate metabolism were downregulated while catabolic ones (PPARA, ACSL1, Glut1, HK1) were upregulated in the ML group. Furthermore, increased acetylation of H3K14 by LPS challenge was reversed by pretreatment with metformin. Conclusion Altogether, our results indicated that pretreatment with metformin dampens LPS-induced inflammatory responses mediated in part by AMPK/NF-κB/NLRP3 signaling and modification of histone H3K14 deacetylation and metabolic changes. Supplementary Information The online version contains supplementary material available at 10.1186/s12917-021-02797-x.
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Affiliation(s)
- Tianle Xu
- College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, People's Republic of China.,Joint International Research Laboratory of Agriculture and Agri-product Safety of Ministry of Education of China, Yangzhou University, Yangzhou, 225009, People's Republic of China
| | - Xinyue Wu
- College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, People's Republic of China.,Joint International Research Laboratory of Agriculture and Agri-product Safety of Ministry of Education of China, Yangzhou University, Yangzhou, 225009, People's Republic of China
| | - Xubin Lu
- College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, People's Republic of China
| | - Yusheng Liang
- Mammalian NutriPhysioGenomics, Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, 61801, USA
| | - Yongjiang Mao
- College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, People's Republic of China
| | - Juan J Loor
- Mammalian NutriPhysioGenomics, Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, 61801, USA
| | - Zhangping Yang
- College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, People's Republic of China. .,Joint International Research Laboratory of Agriculture and Agri-product Safety of Ministry of Education of China, Yangzhou University, Yangzhou, 225009, People's Republic of China.
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El-Massry A, Doheim MF, Iqbal M, Fawzy O, Said OM, Yousif MO, Badawi AE, Tawfik A, Abousamra A. Association Between Keratoconus and Thyroid Gland Dysfunction: A Cross-Sectional Case-Control Study. J Refract Surg 2021; 36:253-257. [PMID: 32267956 DOI: 10.3928/1081597x-20200226-03] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2019] [Accepted: 02/25/2020] [Indexed: 11/20/2022]
Abstract
PURPOSE To examine the clinical association between thyroid gland dysfunction and keratoconus. METHODS This was a cross-sectional case-control study conducted between May 2018 and July 2019. After performing Pentacam (Oculus Optikgeräte GmbH, Wetzlar, Germany) examination, flat, steep, and maximum simulated keratometric readings were recorded for each patient. Serum concentrations of free triiodothyronine, free thyroxine, and thyroid-stimulating hormone were measured. Further examinations by an endocrinologist were indicated for patients with positive laboratory results to confirm thyroid gland dysfunction. RESULTS One hundred eighty-seven patients with bilateral keratoconus and 187 sex- and age-matched healthy controls without keratoconus were analyzed. Mean age was 26.4 ± 8.2 years for the patients with keratoconus and 27.1 ± 9.4 years for the control patients, with no significant difference. The results showed that thyroid gland dysfunction prevalence was 10 of 187 patients with keratoconus (5.3%) and 2 of 187 control patients (1.1%), and the difference was statistically significant (P = .036). For the patients with keratoconus and thyroid gland dysfunction, 8 were women and 2 were men. Additionally, 6 patients (2 men and 4 women) had hyperthyrosis and 4 women had hypothyrosis. For controls, the two patients had hypothyrosis. CONCLUSIONS This study showed that there is a possible association between keratoconus and thyroid gland dysfunction, but more studies are needed to build upon these results. [J Refract Surg. 2020;36(4):253-257.].
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Fried LP, Cohen AA, Xue QL, Walston J, Bandeen-Roche K, Varadhan R. The physical frailty syndrome as a transition from homeostatic symphony to cacophony. NATURE AGING 2021; 1:36-46. [PMID: 34476409 PMCID: PMC8409463 DOI: 10.1038/s43587-020-00017-z] [Citation(s) in RCA: 286] [Impact Index Per Article: 71.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 12/07/2020] [Indexed: 12/14/2022]
Abstract
Frailty in aging marks a state of decreased reserves resulting in increased vulnerability to adverse outcomes when exposed to stressors. This Perspective synthesizes the evidence on the aging-related pathophysiology underpinning the clinical presentation of physical frailty as a phenotype of a clinical syndrome that is distinct from the cumulative-deficit-based frailty index. We focus on integrating the converging evidence on the conceptualization of physical frailty as a state, largely independent of chronic diseases, that emerges when the dysregulation of multiple interconnected physiological and biological systems crosses a threshold to critical dysfunction, severely compromising homeostasis. Our exegesis posits that the physiology underlying frailty is a critically dysregulated complex dynamical system. This conceptual framework implies that interventions such as physical activity that have multisystem effects are more promising to remedy frailty than interventions targeted at replenishing single systems. We then consider how this framework can drive future research to further understanding, prevention and treatment of frailty, which will likely preserve health and resilience in aging populations.
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Affiliation(s)
- Linda P. Fried
- Columbia University Mailman School of Public Health, New York, NY, USA
| | - Alan A. Cohen
- Groupe de recherche PRIMUS, Department of Family Medicine, Université de Sherbrooke, Quebec City, Quebec, Canada
| | - Qian-Li Xue
- Johns Hopkins Center on Aging and Health, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jeremy Walston
- School of Medicine, Johns Hopkins University, Baltimore, MD, USA
| | - Karen Bandeen-Roche
- Johns Hopkins Center on Aging and Health, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
- These authors jointly supervised this work: Karen Bandeen-Roche, Ravi Varadhan
| | - Ravi Varadhan
- Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA
- These authors jointly supervised this work: Karen Bandeen-Roche, Ravi Varadhan
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van der Spoel E, Roelfsema F, van Heemst D. Within-Person Variation in Serum Thyrotropin Concentrations: Main Sources, Potential Underlying Biological Mechanisms, and Clinical Implications. Front Endocrinol (Lausanne) 2021; 12:619568. [PMID: 33716972 PMCID: PMC7945716 DOI: 10.3389/fendo.2021.619568] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Accepted: 01/08/2021] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Individuals exhibit fluctuations in the concentration of serum thyroid-stimulating hormone (TSH) over time. The scale of these variations ranges from minutes to hours, and from months to years. The main factors contributing to the observed within-person fluctuations in serum TSH comprise pulsatile secretion, circadian rhythm, seasonality, and ageing. In clinical practice and clinical research however, such within-person biological variation in serum TSH concentrations is often not considered. The aim of this review is to present an overview of the main sources of within-person variation in TSH levels, as well as the potential underlying biological mechanisms, and the clinical implications. SUMMARY In euthyroid individuals, the circadian rhythm, with a nocturnal surge around 02:00-04:00 h and a nadir during daytime has the greatest impact on variations in serum TSH concentrations. Another source of within-person variation in TSH levels is seasonality, with generally higher levels during the cold winter months. Since TSH is secreted in a pulsatile manner, TSH levels also fluctuate over minutes. Furthermore, elevated TSH levels have been observed with ageing. Other factors that affect TSH levels include thyroid peroxidase (TPO)-antibody positivity, BMI, obesity, smoking, critical illness, and many xenobiotics, including environmental pollutants and drugs. Potential underlying biological mechanisms of within-person variation in TSH levels can be safely concluded from the ability of TSH to respond quickly to changes in cues from the internal or external environment in order to maintain homeostasis. Such cues include the biological clock, environmental temperature, and length of day. The observed increase in TSH level with ageing can be explained at a population level and at an organism level. In clinical practice, the season for thyroid testing can influence a patient's test result and it occurs frequently that subclinical hypothyroid patients normalize to euthyroid levels over time without intervention. CONCLUSIONS Serum TSH concentrations vary over time within an individual, which is caused by multiple different internal and external factors. It is important to take the within-person variations in serum TSH concentrations into account when testing a patient in clinical practice, but also in performing clinical research.
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Affiliation(s)
- Evie van der Spoel
- Section Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
- *Correspondence: Evie van der Spoel,
| | - Ferdinand Roelfsema
- Section Endocrinology, Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
| | - Diana van Heemst
- Section Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
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Pratap UP, Hima L, Kannan T, Thyagarajan C, Priyanka HP, Vasantharekha R, Pushparani A, Thyagarajan S. Sex-Based Differences in the Cytokine Production and Intracellular Signaling Pathways in Patients With Rheumatoid Arthritis. Arch Rheumatol 2020; 35:545-557. [PMID: 33758811 PMCID: PMC7945702 DOI: 10.46497/archrheumatol.2020.7481] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Accepted: 11/26/2019] [Indexed: 12/12/2022] Open
Abstract
Objectives
This study aims to investigate lymphoproliferation, cytokine production, and intracellular signaling molecules in peripheral blood mononuclear cells (PBMCs) isolated from healthy individuals and rheumatoid arthritis (RA) patients to understand the extent of the involvement of these pathways in the pathogenesis of RA. Patients and methods
The study included 65 participants (29 males, 36 females; mean age 51.8±10.3 years; range, 37 to 71 years) who were categorized into four groups as healthy males (n=22, mean age 49.8±10.6 years; range, 39 to 65 years), male RA patients (n=7, mean age 51.8±13.9 years; range, 37 to 68 years), healthy females (n=20, mean age 53.7±8.8 years; range, 42 to 67 years), and female RA patients (n=16, mean age 52.9±10.4 years; range, 40 to 71 years). PBMCs were collected from the participants and analyzed for Concanavalin A (Con A)-induced lymphoproliferation using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cytokine production, and phospho-signal transducer and activator of transcription 3 (p-STAT-3), phospho-extracellular-signal-regulated kinase (p-ERK), phospho-cAMP response element binding (p-CREB), and phospho-protein kinase B expressions using enzyme-linked immunosorbent assay. Short form of the Arthritis Impact Measurement Scales 2 and multidimensional health assessment questionnaire were used to measure the level of disability and the quality of life. Results
In RA patients, production of Con A-induced interleukin (IL)-2 and IL-17 was higher in both sexes while interferon-gamma levels decreased in RA females alone. Expression of p-STAT-3 in PBMCs increased in RA males while it was unaltered in RA females. p-ERK expression was not altered while p-CREB expression was enhanced in RA males and females. Protein-protein interaction analyses demonstrated that these and other key signaling molecules were dysregulated in RA patients. Conclusion Our results suggest that sex-based differences in RA pathogenesis result from differential alterations in signaling pathways to influence the inflammatory process.
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Affiliation(s)
- Uday P Pratap
- Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Lalgi Hima
- Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Thangamani Kannan
- Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Chadrasekaran Thyagarajan
- Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Hannah P Priyanka
- Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Ramasamy Vasantharekha
- Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Anand Pushparani
- Department of Anesthesiology, SRM Medical College and Research Center, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Srinivasan Thyagarajan
- Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
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Burini RC, Anderson E, Durstine JL, Carson JA. Inflammation, physical activity, and chronic disease: An evolutionary perspective. SPORTS MEDICINE AND HEALTH SCIENCE 2020; 2:1-6. [PMID: 35783338 PMCID: PMC9219305 DOI: 10.1016/j.smhs.2020.03.004] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Revised: 03/11/2020] [Accepted: 03/20/2020] [Indexed: 12/17/2022] Open
Abstract
Low-grade inflammation is emerging as a common feature of contemporary metabolic, psychiatric, and neurodegenerative diseases. Both physical inactivity and abdominal adiposity are associated with persistent systemic low-grade inflammation. Thus, the behavioral, biological, and physiological changes that cause a predisposition to obesity and other co-morbidities could have epigenetic underpinnings in addition to various evolutionary scenarios. A key assumption involves the potential for a mismatch between the human genome molded over generations, and the issue of adapting to the modern high calorie diet and common built environments promoting inactivity. This biological mismatch appears to have dire health consequences. Therefore, the goal of this article is to provide a brief overview on the importance of inflammation as part of human survival and how physical activity (PA) and physical inactivity are critical regulators of systemic inflammation. The review will highlight anti-inflammatory effects of PA and exercise training from a metabolic and systemic signaling perspective, which includes skeletal muscle to utilization of fatty acids, TLR4 signaling, and myokine/adipokine effects. The available evidence suggests that PA, regular exercise, and weight loss offer both protection against and treatment for a wide variety of chronic diseases associated with low-grade inflammation through an improved inflammatory profile.
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Affiliation(s)
| | - Elizabeth Anderson
- Arnold School of Public Health, Department of Exercise Science, University of South Carolina, Columbia, SC, USA
| | - J. Larry Durstine
- Arnold School of Public Health, Department of Exercise Science, University of South Carolina, Columbia, SC, USA
| | - James A. Carson
- College of Health Professions, Division of Rehabilitation Science, University of Tennessee Health Science Center, Memphis, TN, USA
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