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Ni Q, Xia L, Huang Y, Yuan X, Gu W, Chen Y, Wang Y, Nian M, Wu S, Cai H, Huang J. Gut microbiota dysbiosis orchestrates vitiligo-related oxidative stress through the metabolite hippuric acid. MICROBIOME 2025; 13:112. [PMID: 40329424 PMCID: PMC12054231 DOI: 10.1186/s40168-025-02102-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 03/26/2025] [Indexed: 05/08/2025]
Abstract
BACKGROUND Vitiligo, a depigmenting autoimmune skin disease characterized by melanocyte dysfunction or death, is known to be associated with an imbalance in gut microbiota. Oxidative stress plays a critical role in the pathogenesis of vitiligo. However, the complex promising interaction between abnormal accumulation of reactive oxygen species (ROS) in the skin and gut microbiota has remained unclear. RESULTS Here, we compared transcriptome data of vitiligo lesions and normal skin and identified a high expression of oxidative stress-related genes in vitiligo lesions. We also established a vitiligo mouse model and found that the presence of gut microbiota influenced the expression of ROS-related genes. Depletion of gut microbiota reduced abnormal ROS accumulation and mitochondrial abnormalities in melanocytes, significantly improving depigmentation. Our findings from manipulating gut microbiota through cohousing, fecal microbiota transplantation (FMT), and probiotic supplementation showed that transferring gut microbiota from mice with severe vitiligo-like phenotypes exacerbated skin depigmentation while probiotics inhibited its progression. Targeted metabolomics of fecal, serum, and skin tissues revealed gut microbiota-dependent accumulation of hippuric acid, mediating excessive ROS in the skin. Elevated serum hippuric acid levels were also confirmed in vitiligo patients. Additionally, a microbiota-dependent increase in intestinal permeability in vitiligo mice mediated elevated hippuric acid levels, and we found that hippuric acid could directly bind to ROS-related proteins (NOS2 and MAPK14). CONCLUSIONS Our results suggested the important role of gut microbiota in regulating vitiligo phenotypes and oxidative stress. We identified hippuric acid, a gut microbiota-host co-metabolite, as a critical mediator of oxidative stress in vitiligo skin and its binding targets (NOS2 and MAPK14), resulting in oxidative stress. Validation in a small human cohort suggested that hippuric acid could serve as a novel diagnostic biomarker and therapeutic target for vitiligo. These findings provided new insights into how gut microbiota regulates skin oxidative stress in vitiligo and suggested potential treatment strategies for the disease. Video Abstract.
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Affiliation(s)
- Qingrong Ni
- Department of Dermatology, Air Force Medical Center, Fourth Military Medical University, Beijing, 100142, China.
- Department of Neurobiology, Basic Medical Science Academy, Fourth Military Medical University, Xi'an, 710032, China.
| | - Lin Xia
- Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, 110016, China
| | - Ye Huang
- Department of Dermatology, Air Force Medical Center, Fourth Military Medical University, Beijing, 100142, China
| | - Xiaoying Yuan
- Department of Dermatology, Air Force Medical Center, Fourth Military Medical University, Beijing, 100142, China
| | - Weijie Gu
- Department of Dermatology, Air Force Medical Center, Fourth Military Medical University, Beijing, 100142, China
| | - Yueqi Chen
- Department of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China
| | - Yijin Wang
- Department of Dermatology, Air Force Medical Center, Fourth Military Medical University, Beijing, 100142, China
| | - Meng Nian
- Department of Neurobiology, Basic Medical Science Academy, Fourth Military Medical University, Xi'an, 710032, China
| | - Shengxi Wu
- Department of Neurobiology, Basic Medical Science Academy, Fourth Military Medical University, Xi'an, 710032, China
| | - Hong Cai
- Department of Dermatology, Air Force Medical Center, Fourth Military Medical University, Beijing, 100142, China.
| | - Jing Huang
- Department of Neurobiology, Basic Medical Science Academy, Fourth Military Medical University, Xi'an, 710032, China.
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Fu S, Xie B, Song X. Neurological Mechanisms Exploration and Therapeutic Targets in Segmental Vitiligo Accompanied by White Hair. Pigment Cell Melanoma Res 2025; 38:e70020. [PMID: 40252009 DOI: 10.1111/pcmr.70020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 03/04/2025] [Accepted: 04/06/2025] [Indexed: 04/21/2025]
Abstract
Vitiligo is the most common skin depigmentation disease, affecting 0.1%-2% of people in the world. 3.5%-20.5% of segmental patients account for the total number of vitiligo patients. It has been clinically observed that segmental vitiligo patients are more likely to generate white hair, which may be related to neuroendocrine factors. The color of human skin and hair is affected by the number and functional status of melanocytes. Vitiligo affects patients' physical and mental health due to the shame it causes from the white patches and hair. This article reviews the underlying mechanisms of segmental vitiligo with white hair based on skin and hair follicle melanocytes. The article attempts to propose possible targets for the treatment of this disease.
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Affiliation(s)
- Shiqi Fu
- Zhejiang Chinese Medical University, Hangzhou, China
| | - Bo Xie
- Department of Dermatology, Hangzhou Third People's Hospital, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China
| | - Xiuzu Song
- Department of Dermatology, Hangzhou Third People's Hospital, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China
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Leiding JW, Mathews CE, Arnold DE, Chen J. The Role of NADPH Oxidase 2 in Leukocytes. Antioxidants (Basel) 2025; 14:309. [PMID: 40227295 PMCID: PMC11939230 DOI: 10.3390/antiox14030309] [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: 01/21/2025] [Revised: 02/18/2025] [Accepted: 02/26/2025] [Indexed: 04/15/2025] Open
Abstract
NADPH oxidase (NOX) family members are major resources of intracellular reactive oxygen species (ROS). In the immune system, ROS derived from phagocytic NOX (NOX2) participate in both pathogen clearance and signaling transduction. The role of NOX2 in neutrophils and macrophages has been well studied as mutations in NOX2 subunits cause chronic granulomas disease (CGD). NOX2 is expressed across a wide range of immune cells and recent reports have demonstrated that NOX2-derived ROS play important roles in other immune cells during an immune response. In this review, we summarize current knowledge of functions of NADPH oxidase 2 in each subset of leukocytes, as well as associations of NOX2 deficiency with diseases associated specifically with autoimmunity and immune deficiency. We also discuss important knowledge gaps as well as potential future directions for NOX2 research.
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Affiliation(s)
- Jennifer W. Leiding
- Division of Allergy and Immunology, John Hopkins University, Baltimore, MD 21218, USA;
- Cancer and Blood Disorders Institute, Johns Hopkins All Children’s Hospital, St. Petersburg, FL 33701, USA
| | - Clayton E. Mathews
- Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA;
- Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Danielle E. Arnold
- Immune Deficiency Cellular Therapy Program, National Cancer Institutes, National Institutes of Health, Bethesda, MD 20892, USA;
| | - Jing Chen
- Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA;
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Alhamar G, Vinci C, Franzese V, Tramontana F, Le Goux N, Ludvigsson J, Nissim A, Strollo R. The role of oxidative post-translational modifications in type 1 diabetes pathogenesis. Front Immunol 2025; 16:1537405. [PMID: 40028329 PMCID: PMC11868110 DOI: 10.3389/fimmu.2025.1537405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Accepted: 01/22/2025] [Indexed: 03/05/2025] Open
Abstract
The pathogenesis of type 1 diabetes (T1D) involves a complex interplay of genetic predisposition, immune processes, and environmental factors, leading to the selective destruction of pancreatic beta-cells by the immune system. Emerging evidence suggests that intrinsic beta-cell factors, including oxidative stress and post-translational modifications (PTM) of beta-cell antigens, may also contribute to their immunogenicity, shedding new light on the multifaceted pathogenesis of T1D. Over the past 30 years, neoepitopes generated by PTMs have been hypothesized to play a role in T1D pathogenesis, but their involvement has only been systematically investigated in recent years. In this review, we explored the interplay between oxidative PTMs, neoepitopes, and T1D, highlighting oxidative stress as a pivotal factor in immune system dysfunction, beta-cell vulnerability, and disease onset.
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Affiliation(s)
- Ghadeer Alhamar
- Department of Immunology and Microbiology, Dasman Diabetes Institute, Dasman, Kuwait
| | - Chiara Vinci
- Center for Diabetes Research, Université Libre de Bruxelles, Brussels, Belgium
| | - Valentina Franzese
- Department for the Promotion of Human Science and Quality of Life, San Raffaele Open University, Rome, Italy
- Department of Medicine, Fondazione Policlinico Universitario Campus Bio-Medico di Roma, Rome, Italy
- Department of Medicine, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Flavia Tramontana
- Department of Medicine, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Nelig Le Goux
- Biochemical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom
| | - Johnny Ludvigsson
- Crown Princess Victoria Children’s Hospital and Division of Pediatrics, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Ahuva Nissim
- Biochemical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom
| | - Rocky Strollo
- Department for the Promotion of Human Science and Quality of Life, San Raffaele Open University, Rome, Italy
- Department of Medicine, Fondazione Policlinico Universitario Campus Bio-Medico di Roma, Rome, Italy
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Chen X, Chen H. Proteomics and transcriptomics combined reveal specific immunological markers in autoimmune thyroid disease. Front Immunol 2025; 15:1531402. [PMID: 39872521 PMCID: PMC11769792 DOI: 10.3389/fimmu.2024.1531402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 12/19/2024] [Indexed: 01/30/2025] Open
Abstract
Objective The pathogenesis of AITD remains unclear to date. This study employs a combination of proteomics and transcriptomics analysis to identify and validate specific immune response markers in patients with hyperthyroidism and hypothyroidism, thereby providing a scientific basis for the clinical diagnosis and treatment of AITD. Methods By collecting serum and whole blood tissue samples from patients with hyperthyroidism, hypothyroidism, and healthy controls, this study utilizes a combination of transcriptomics and proteomics to analyze changes in immune-related signaling molecules in patients. Specific biomarkers were identified, and the ELISA method was employed to determine the expression levels of these clinical markers and their correlation with clinical features of the patients, ultimately establishing a predictive model. Results Transcriptomic and proteomic analyses were conducted to identify differentially expressed genes and proteins in patients with hyperthyroidism and hypothyroidism compared to healthy controls. Enrichment analysis revealed that these differentially expressed genes and proteins are primarily associated with immune function, antigen-antibody binding, and alterations in immune cells. Through the combined analysis of transcriptomics and proteomics, key genes IGHG3, ISG15, and ZNF683 were identified. ELISA results from clinical patient serum samples indicated that the levels of IGHG3 were significantly higher in both the hyperthyroid and hypothyroid groups compared to the control group (P<0.05). Additionally, the serum levels of ISG15 in the hyperthyroid group were greater than those in both the control and hypothyroid groups (P<0.05), while the serum levels of ZNF683 in the hypothyroid group exceeded those in the control and hyperthyroid groups (P<0.05). Furthermore, all three biomarkers correlated with the thyroid function of the patients. Prediction models for hyperthyroid and hypothyroid patients were constructed using IGHG3, ISG15, and ZNF683, demonstrating good performance metrics and decision effect. Conclusion In patients with hyperthyroidism and hypothyroidism, significant changes primarily occur in immune function and immune cells when compared to healthy individuals. Key signaling molecules were identified: ISG15 for hyperthyroidism, ZNF683 for hypothyroidism, and IGHG3 common to both conditions. These findings provide new biomarkers for the diagnosis and monitoring of clinical patients, thereby offering a scientific basis for research on AITD and personalized treatment approaches.
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Affiliation(s)
- Xia Chen
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, China
| | - Hui Chen
- Department of Endocrinology and Metabolism, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, China
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Liang X, Guo F, Fan Q, Cai X, Wang J, Chen J, Liu F, Du Y, Chen Y, Li X. Healthy lifestyle choices: new insights into vitiligo management. Front Immunol 2024; 15:1440705. [PMID: 39624091 PMCID: PMC11609173 DOI: 10.3389/fimmu.2024.1440705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 10/16/2024] [Indexed: 01/03/2025] Open
Abstract
Background The treatment of vitiligo is complex, and providing guidance based on lifestyle habits is a good option that has not been summarized or analyzed. Objective To elucidate the relationship between vitiligo and lifestyle factors. Methods Four databases (PubMed, Embase, Cochrane, and China National Knowledge Internet) were searched for articles published between 1980 and December 2022. Keywords such as smoking, drinking, exercise, diet, and sleep were used. Results Based on the search strategy, 875 relevant studies were retrieved, and 73 were included in this study, of which 41 studies with 8,542 patients with vitiligo were included in the meta-analysis. Vitamin C [mean difference (MD), -0.342; 95% confidence interval (CI), -1.090-0.407; p >0.05), folic acid (MD, -1.463; 95% CI, -7.133-4.208; p >0.05), and selenium (MD, 0.350; 95% CI, -0.687-1.387; p >0.05) levels did not differ between the groups. Vitamin E (MD, -1.408; 95% CI, -2.611--0.206; p <0.05), vitamin B12 (MD, -0.951; 95% CI, -1.672--0.275; p <0.05), copper (MD, -0.719; 95% CI, -1.185--0.252, p <0.005), and zinc (MD, -0.642; 95% CI, -0.731--0.554; p <0.001) levels were lower in the vitiligo group than in the control group. The serum iron level of the vitiligo group was significantly higher than that of the control group (MD, 1.181; 95% CI, 0.390-1.972; p <0.005). Finally, more participants in the vitiligo group smoked and drank alcohol than those in the control group. Limitations Most studies are from Eastern countries; thus, extrapolating these results to Western populations is questionable. The significant heterogeneity may be attributed to the different stages, types, duration, center settings, population registries, etc., which seriously impair the validity of the results. Conclusions Patients with vitiligo should reduce smoking and alcohol consumption and take appropriate vitamin E, B12, copper, and zinc supplements. However, vitamin C, vitamin D, selenium, iron, and folic acid supplements are unnecessary. Moreover, they should consider sun protection and avoid permanent hair dye use. Patients with vitiligo may experience sleep disturbances and sexual dysfunction, and these patients should seek help from a specialist if necessary. Systematic review registration https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42023480757.
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Affiliation(s)
- Xin Liang
- Chinese Medicine Department, Songnan Town Community Health Service Center, Shanghai, China
| | - Fei Guo
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Qian Fan
- Chinese Medicine Department, Songnan Town Community Health Service Center, Shanghai, China
| | - Xiaoce Cai
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jiao Wang
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jiale Chen
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Fang Liu
- Chinese Medicine Department, Songnan Town Community Health Service Center, Shanghai, China
| | - Yuhua Du
- Chinese Medicine Department, Songnan Town Community Health Service Center, Shanghai, China
| | - Yan Chen
- Chinese Medicine Department, Songnan Town Community Health Service Center, Shanghai, China
| | - Xin Li
- Chinese Medicine Department, Songnan Town Community Health Service Center, Shanghai, China
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
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Teng M, Wu TJ, Jing X, Day BW, Pritchard KA, Naylor S, Teng RJ. Temporal Dynamics of Oxidative Stress and Inflammation in Bronchopulmonary Dysplasia. Int J Mol Sci 2024; 25:10145. [PMID: 39337630 PMCID: PMC11431892 DOI: 10.3390/ijms251810145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 09/04/2024] [Accepted: 09/20/2024] [Indexed: 09/30/2024] Open
Abstract
Bronchopulmonary dysplasia (BPD) is the most common lung complication of prematurity. Despite extensive research, our understanding of its pathophysiology remains limited, as reflected by the stable prevalence of BPD. Prematurity is the primary risk factor for BPD, with oxidative stress (OS) and inflammation playing significant roles and being closely linked to premature birth. Understanding the interplay and temporal relationship between OS and inflammation is crucial for developing new treatments for BPD. Animal studies suggest that OS and inflammation can exacerbate each other. Clinical trials focusing solely on antioxidants or anti-inflammatory therapies have been unsuccessful. In contrast, vitamin A and caffeine, with antioxidant and anti-inflammatory properties, have shown some efficacy, reducing BPD by about 10%. However, more than one-third of very preterm infants still suffer from BPD. New therapeutic agents are needed. A novel tripeptide, N-acetyl-lysyltyrosylcysteine amide (KYC), is a reversible myeloperoxidase inhibitor and a systems pharmacology agent. It reduces BPD severity by inhibiting MPO, enhancing antioxidative proteins, and alleviating endoplasmic reticulum stress and cellular senescence in a hyperoxia rat model. KYC represents a promising new approach to BPD treatment.
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Affiliation(s)
- Michelle Teng
- Department of Pediatrics, Medical College of Wisconsin, Suite C410, Children Corporate Center, 999N 92nd Street, Milwaukee, WI 53226, USA; (M.T.); (T.-J.W.); (X.J.)
- Children’s Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd., Wauwatosa, WI 53226, USA;
| | - Tzong-Jin Wu
- Department of Pediatrics, Medical College of Wisconsin, Suite C410, Children Corporate Center, 999N 92nd Street, Milwaukee, WI 53226, USA; (M.T.); (T.-J.W.); (X.J.)
- Children’s Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd., Wauwatosa, WI 53226, USA;
| | - Xigang Jing
- Department of Pediatrics, Medical College of Wisconsin, Suite C410, Children Corporate Center, 999N 92nd Street, Milwaukee, WI 53226, USA; (M.T.); (T.-J.W.); (X.J.)
- Children’s Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd., Wauwatosa, WI 53226, USA;
| | - Billy W. Day
- ReNeuroGen LLC, 2160 San Fernando Dr., Elm Grove, WI 53122, USA; (B.W.D.); (S.N.)
| | - Kirkwood A. Pritchard
- Children’s Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd., Wauwatosa, WI 53226, USA;
- ReNeuroGen LLC, 2160 San Fernando Dr., Elm Grove, WI 53122, USA; (B.W.D.); (S.N.)
- Department of Surgery, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA
| | - Stephen Naylor
- ReNeuroGen LLC, 2160 San Fernando Dr., Elm Grove, WI 53122, USA; (B.W.D.); (S.N.)
| | - Ru-Jeng Teng
- Department of Pediatrics, Medical College of Wisconsin, Suite C410, Children Corporate Center, 999N 92nd Street, Milwaukee, WI 53226, USA; (M.T.); (T.-J.W.); (X.J.)
- Children’s Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd., Wauwatosa, WI 53226, USA;
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Le J, Meng Y, Wang Y, Li D, Zeng F, Xiong Y, Chen X, Deng G. Molecular and therapeutic landscape of ferroptosis in skin diseases. Chin Med J (Engl) 2024; 137:1777-1789. [PMID: 38973265 PMCID: PMC12077552 DOI: 10.1097/cm9.0000000000003164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Indexed: 07/09/2024] Open
Abstract
ABSTRACT Regulated cell death (RCD) is a critical physiological process essential in maintaining skin homeostasis. Among the various forms of RCD, ferroptosis stands out due to its distinct features of iron accumulation, lipid peroxidation, and involvement of various inhibitory antioxidant systems. In recent years, an expanding body of research has solidly linked ferroptosis to the emergence of skin disorders. Therefore, understanding the mechanisms underlying ferroptosis in skin diseases is crucial for advancing therapy and prevention strategies. This review commences with a succinct elucidation of the mechanisms that underpin ferroptosis, embarks on a thorough exploration of ferroptosis's role across a spectrum of skin conditions, encompassing melanoma, psoriasis, systemic lupus erythematosus (SLE), vitiligo, and dermatological ailments precipitated by ultraviolet (UV) exposure, and scrutinizes the potential therapeutic benefits of pharmacological interventions aimed at modulating ferroptosis for the amelioration of skin diseases.
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Affiliation(s)
- Jiayuan Le
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, Hunan 410008, China
- Furong Laboratory, Changsha, Hunan 410008, China
- Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan 410008, China
| | - Yu Meng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, Hunan 410008, China
- Furong Laboratory, Changsha, Hunan 410008, China
- Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan 410008, China
| | - Ying Wang
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, Hunan 410008, China
- Furong Laboratory, Changsha, Hunan 410008, China
- Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan 410008, China
| | - Daishi Li
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, Hunan 410008, China
- Furong Laboratory, Changsha, Hunan 410008, China
- Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan 410008, China
| | - Furong Zeng
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Yixiao Xiong
- Department of Dermatology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Xiang Chen
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, Hunan 410008, China
- Furong Laboratory, Changsha, Hunan 410008, China
- Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan 410008, China
| | - Guangtong Deng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, Hunan 410008, China
- Furong Laboratory, Changsha, Hunan 410008, China
- Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan 410008, China
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li W, Pang Y, He Q, Song Z, Xie X, Zeng J, Guo J. Exosome-derived microRNAs: emerging players in vitiligo. Front Immunol 2024; 15:1419660. [PMID: 39040109 PMCID: PMC11260631 DOI: 10.3389/fimmu.2024.1419660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 06/24/2024] [Indexed: 07/24/2024] Open
Abstract
Exosome-derived microRNAs (miRNAs) are biomacromolecules and nanoscale extracellular vesicles originating from intracellular compartments that are secreted by most cells into the extracellular space. This review examines the formation and function of exosomal miRNAs in biological information transfer, explores the pathogenesis of vitiligo, and highlights the relationship between exosomal miRNAs and vitiligo. The aim is to deepen the understanding of how exosomal miRNAs influence immune imbalance, oxidative stress damage, melanocyte-keratinocyte interactions, and melanogenesis disorders in the development of vitiligo. This enhanced understanding may contribute to the development of potential diagnostic and therapeutic options for vitiligo.
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Affiliation(s)
- Wenquan li
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Dermatological Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yaobin Pang
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Dermatological Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qingying He
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Dermatological Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Zongzou Song
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Dermatological Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xin Xie
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Dermatological Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jinhao Zeng
- Dermatological Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jing Guo
- Dermatological Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Hu W, Wang H, Li K, Lei Z, Xiang F, Li J, Kang X. Identification of active compounds in Vernonia anthelmintica (L.) willd by targeted metabolome MRM and kaempferol promotes HaCaT cell proliferation and reduces oxidative stress. Front Pharmacol 2024; 15:1343306. [PMID: 38659590 PMCID: PMC11041372 DOI: 10.3389/fphar.2024.1343306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 03/27/2024] [Indexed: 04/26/2024] Open
Abstract
Introduction: Vernonia anthelmintica (L.) Willd. is a traditional treatment for vitiligo in Xinjiang. However, its therapeutic mechanism remains unclear owing to its complex composition and limited research on its chemical profile. Methods: We employed a targeted metabolome approach, combining selective reaction monitoring/multiple response monitoring (SRM/MRM) with high-performance liquid chromatography and MRM mass spectrometry to quantitatively analyze the flavonoid constituents of Vernonia anthelmintica. We also used network pharmacology and molecular docking to identify potential vitiligo-linked compounds and targets of V. anthelmintica seeds. Additionally, we assessed HaCaT cell proliferation by AAPH-induced, alongside changes in SOD activity and MDA content, following treatment with V. anthelmintica components. Finally, flow cytometry was used to detect apoptosis and ROS levels. Results and Discussion: We identified 36 flavonoid compounds in V. anthelmintica seeds, with 14 compounds exhibiting druggability. AKT1, VEGFA, ESR1, PTGS2, and IL2 have been identified as key therapeutic target genes, with PI3K/AKT signaling being an important pathway. Notably, kaempferol, one of the identified compounds, exhibited high expression in network pharmacology analysis. Kaempferol exhibited a strong binding affinity to important targets. Further, kaempferol enhanced HaCaT cell viability, inhibited apoptosis, reduced MDA levels, suppressed ROS activity, and upregulated SOD activity, increase the expression of cellular antioxidant genes, including HO-1, GCLC, GCLM, Nrf2, NQO1 and Keap1, providing significant protection against oxidative stress damage in vitro. Here, we present the first comprehensive study integrating SRM/MRM approaches and network analysis to identify active flavonoid compounds within V. anthelmintica (L.) Willd. Moreover, we revealed that its active ingredient, kaempferol, offers protection against AAPH-induced damage in keratinocytes, highlighting its potential as a clinical resource.
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Affiliation(s)
- Wen Hu
- Department of Dermatology and Venereology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
- Xinjiang Clinical Research Center for Dermatologic Diseases, Urumqi, China
- Xinjiang Key Laboratory of Dermatology Research (XJYS1707), Urumqi, China
| | - Hongjuan Wang
- Department of Dermatology and Venereology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
- Xinjiang Clinical Research Center for Dermatologic Diseases, Urumqi, China
- Xinjiang Key Laboratory of Dermatology Research (XJYS1707), Urumqi, China
| | - Kaixiao Li
- Department of Dermatology and Venereology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
- Xinjiang Clinical Research Center for Dermatologic Diseases, Urumqi, China
- Xinjiang Key Laboratory of Dermatology Research (XJYS1707), Urumqi, China
| | - Zixian Lei
- Department of Dermatology and Venereology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
- Xinjiang Clinical Research Center for Dermatologic Diseases, Urumqi, China
- Xinjiang Key Laboratory of Dermatology Research (XJYS1707), Urumqi, China
| | - Fang Xiang
- Department of Dermatology and Venereology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
- Xinjiang Clinical Research Center for Dermatologic Diseases, Urumqi, China
- Xinjiang Key Laboratory of Dermatology Research (XJYS1707), Urumqi, China
| | - Jun Li
- Department of Dermatology and Venereology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
- Xinjiang Clinical Research Center for Dermatologic Diseases, Urumqi, China
- Xinjiang Key Laboratory of Dermatology Research (XJYS1707), Urumqi, China
| | - Xiaojing Kang
- Department of Dermatology and Venereology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
- Xinjiang Clinical Research Center for Dermatologic Diseases, Urumqi, China
- Xinjiang Key Laboratory of Dermatology Research (XJYS1707), Urumqi, China
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Kouchaki E, Rafiei H, Ghaderi A, Azadchehr MJ, Safa F, Omidian K, Khodabakhshi A, Vahid F, Rezapoor-Kafteroodi B, Banafshe HR, Safa N. Effects of crocin on inflammatory biomarkers and mental health status in patients with multiple sclerosis: A randomized, double-blinded clinical trial. Mult Scler Relat Disord 2024; 83:105454. [PMID: 38306888 DOI: 10.1016/j.msard.2024.105454] [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: 12/27/2023] [Revised: 01/08/2024] [Accepted: 01/18/2024] [Indexed: 02/04/2024]
Abstract
BACKGROUND Multiple sclerosis (MS), as a demyelinating disease correlated with inflammation and oxidative stress, affects the central nervous system and causes a wide range of complications, including psychiatric disorders. Considering the anti-inflammatory and antioxidant properties associated with the bioactive components of saffron, such as crocin (trans-crocetin bis(β-d-gentiobiosyl) ester), and their potential impact on ameliorating psychiatric symptoms, our study aimed to investigate the effect of crocin on biomarkers of inflammation, oxidative stress, and mental health, e.g., depression and anxiety in individuals with MS. METHOD Patients with MS were randomized into two groups, taking either 15 mg crocin tablets twice a day (n = 25; 30 mg/day) or placebo tablets (n = 25) for 8 weeks. The valid and reliable Beck depression and anxiety scale questionnaire was recorded, and fasting blood samples were collected to measure biomarkers, including high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), and nitric oxide (NO) at baseline and week 8 following the intervention. RESULTS The data analysis using ANCOVA showed that supplementation with crocin for 8 weeks significantly lowered hs-CRP levels (p-value= 0.01). In addition, within-group comparisons showed crocin significantly decreased anxiety (p-value= 0.01). However, crocin did not affect serum MDA and NO after 8 weeks of intervention. CONCLUSION Our findings suggest that crocin may keep promise in attenuating inflammation, evidenced by reducing hs-CRP in patients with MS. However, supplementation for 8 weeks may not be sufficient to improve mental health, and future clinical studies with higher sample sizes and various doses and durations are recommended.
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Affiliation(s)
- Ebrahim Kouchaki
- Department of Neurology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Hossein Rafiei
- College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Amir Ghaderi
- Department of Addiction Studies, School of Medical and Clinical Research Development Unit-Matini/Kargarnejad Hospital, Kashan University of Medical Sciences, Kashan, Iran
| | | | - Fateme Safa
- Department of Nutrition, Faculty of Public Health, Kerman University of Medical Sciences, Kerman, Iran
| | - Kosar Omidian
- College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Adeleh Khodabakhshi
- Department of Nutrition, Faculty of Public Health, Kerman University of Medical Sciences, Kerman, Iran; Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran
| | - Farhad Vahid
- Nutrition and Health Group, Department of Precision Health, Luxembourg Institute of Health, Strassen, Luxembourg
| | | | - Hamid-Reza Banafshe
- Department of Pharmacology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Nasim Safa
- Department of Neurology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.
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Singh S. Antioxidant nanozymes as next-generation therapeutics to free radical-mediated inflammatory diseases: A comprehensive review. Int J Biol Macromol 2024; 260:129374. [PMID: 38242389 DOI: 10.1016/j.ijbiomac.2024.129374] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 12/30/2023] [Accepted: 01/08/2024] [Indexed: 01/21/2024]
Abstract
Recent developments in exploring the biological enzyme mimicking properties in nanozymes have opened a separate avenue, which provides a suitable alternative to the natural antioxidants and enzymes. Due to high and tunable catalytic activity, low cost of synthesis, easy surface modification, and good biocompatibility, nanozymes have garnered significant research interest globally. Several inorganic nanomaterials have been investigated to exhibit catalytic activities of some of the key natural enzymes, including superoxide dismutase (SOD), catalase, glutathione peroxidase, peroxidase, and oxidase, etc. These nanozymes are used for diverse biomedical applications including therapeutics, imaging, and biosensing in various cells/tissues and animal models. In particular, inflammation-related diseases are closely associated with reactive oxygen and reactive nitrogen species, and therefore effective antioxidants could be excellent therapeutics due to their free radical scavenging ability. Although biological enzymes and other artificial antioxidants could perform well in scavenging the reactive oxygen and nitrogen species, however, suffer from several drawbacks such as the requirement of strict physiological conditions for enzymatic activity, limited stability in the environment beyond their optimum pH and temperature, and high cost of synthesis, purification, and storage make then unattractive for broad-spectrum applications. Therefore, this review systematically and comprehensively presents the free radical-mediated evolution of various inflammatory diseases (inflammatory bowel disease, mammary gland fibrosis, and inflammation, acute injury of the liver and kidney, mammary fibrosis, and cerebral ischemic stroke reperfusion) and their mitigation by various antioxidant nanozymes in the biological system. The mechanism of free radical scavenging by antioxidant nanozymes under in vitro and in vivo experimental models and catalytic efficiency comparison with corresponding natural enzymes has also been presented.
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Affiliation(s)
- Sanjay Singh
- National Institute of Animal Biotechnology (NIAB), Opposite Journalist Colony, Near Gowlidoddy, Extended Q-City Road, Gachibowli, Hyderabad 500032, Telangana, India.
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Ndayambaje M, Wahnou H, Sow M, Chgari O, Habyarimana T, Karkouri M, Limami Y, Naya A, Oudghiri M. Exploring the multifaceted effects of Ammi visnaga: subchronic toxicity, antioxidant capacity, immunomodulatory, and anti-inflammatory activities. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART A 2024; 87:150-165. [PMID: 38037686 DOI: 10.1080/15287394.2023.2289430] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/02/2023]
Abstract
Ammi visnaga (A. visnaga) is an annual herb that has been used in traditional medicine to treat various ailments attributed to the presence of its bioactive compounds. The purpose of this study was to identify and examine the phytochemical properties of the hydroalcoholic extract of A. visnaga using in vitro and in vivo models. Our findings demonstrated that the extract contained a variety of beneficial components, including phenols, flavonoids, tannins, coumarins, saponins, khellin, and visnagin. The total polyphenolic content and total flavonoid content were 23.26 mg/GAE/g dry weight and 13.26 mg/GAE/g dry weight, respectively. In vitro tests demonstrated that the extract possessed antioxidant properties as evidenced by the ability to scavenge free radicals, including DPPH, ABTS, nitric oxide (NO), phosphomolybdate, and ferric-reducing antioxidant power (FRAP). Further, the extract was found to inhibit hydrogen peroxide (H2O2)-induced hemolysis. In a 90-d in vivo study, female Wistar rats were administered 1 g/kg of A. visnaga extract orally resulting in a significant increase in total white blood cell count. Although morphological changes were observed in the liver, no marked alterations were noted in kidneys and spleen. In a female Swiss albino mice model of acetic acid-induced vascular permeability, A. visnaga significantly inhibited extravasations of Evans blue at doses of 0.5 or 1 g/kg with inhibition percentages of 51 and 65%, respectively, blocking tissue necrosis. The extract also demonstrated potential immunomodulatory properties in mice by enhancing antibody production in response to antigens. In silico molecular docking studies demonstrated a strong affinity between khellin or visnagin and immunomodulatory proteins, NF-κB, p52, and TNF-α. These findings suggest that A. visnaga may be considered a beneficial antioxidant with immunomodulatory properties and might serve as a therapeutic agent to combat certain diseases.
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Affiliation(s)
- Martin Ndayambaje
- Laboratory of Immunology and Biodiversity, Faculty of Sciences Ain Chock, Hassan II University of Casablanca, Casablanca, Morocco
| | - Hicham Wahnou
- Laboratory of Immunology and Biodiversity, Faculty of Sciences Ain Chock, Hassan II University of Casablanca, Casablanca, Morocco
| | - Marieme Sow
- Laboratory of Immunology and Biodiversity, Faculty of Sciences Ain Chock, Hassan II University of Casablanca, Casablanca, Morocco
| | - Oumaima Chgari
- Laboratory of Immunology and Biodiversity, Faculty of Sciences Ain Chock, Hassan II University of Casablanca, Casablanca, Morocco
| | | | - Mehdi Karkouri
- Cellular and Molecular Pathology Laboratory, Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
| | - Youness Limami
- Laboratory of Immunology and Biodiversity, Faculty of Sciences Ain Chock, Hassan II University of Casablanca, Casablanca, Morocco
- Laboratory of Health Sciences and Technologies, Higher Institute of Health Sciences, Hassan First University of Settat, Settat, Morocco
| | - Abdallah Naya
- Laboratory of Immunology and Biodiversity, Faculty of Sciences Ain Chock, Hassan II University of Casablanca, Casablanca, Morocco
| | - Mounia Oudghiri
- Laboratory of Immunology and Biodiversity, Faculty of Sciences Ain Chock, Hassan II University of Casablanca, Casablanca, Morocco
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Li C, Li X, Zhang Z. Oxidative stress and pro-inflammatory cytokines following perchloroethylene exposure in young female dry-cleaning workers. Work 2024; 77:975-979. [PMID: 37781844 DOI: 10.3233/wor-230080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/03/2023] Open
Abstract
BACKGROUND The involvement of Perchloroethylene (PCE) in the development of autoimmune diseases has been reported. However, few studies investigated immunotoxicity in PCE-exposed workers. OBJECTIVE To study changes in the oxidative stress and cytokine profile of young female dry-cleaning workers exposed to PCE. METHODS Thirty-eight exposed workers and 38 unexposed controls were recruited. All the participants were young nonsmoker females. Individual interviews were conducted by a physician. Blood samples were collected and hematological tests were performed by an automated Coulter Counter. Plasma PCE levels were determined using gas chromatography/flame ionization detection. Plasma total antioxidant capacity (TAC), Catalase (CAT), Superoxide dismutase (SOD), and Malondialdehyde (MDA) levels were measured using the colorimetric method. The levels of plasma cytokines interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-8, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured by commercially kits. RESULTS The levels of plasma PCE averaged 561±96 ng/ml in the exposed group compared with 1.3±0.5 ng/ml in the controls. The hematological tests failed to find abnormalities in the exposed workers. Exposed workers presented significantly increased plasma levels of MDA, SOD and CAT. There were no significant differences between the two groups for level of plasma TAC. Significantly increased plasma IL-1β and TNF-α and decreased IL-2 and IL-8 levels were seen in the exposed workers. There were no significant differences between the two groups for IL-4, IL-6, and IFN-γ. CONCLUSION PCE exposure resulted in changed cytokine profile in dry-cleaning workers, suggesting the potential immunotoxicity of PCE at low exposure levels.
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Affiliation(s)
- Changhao Li
- School of Public Health, Soochow University, Suzhou, China
| | - Xinyu Li
- School of Public Health, Soochow University, Suzhou, China
| | - Zengli Zhang
- School of Public Health, Soochow University, Suzhou, China
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15
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Yetim E, Eren MA, Karaaslan H, Sabuncu T. Higher Levels of Plasma Fetuin-A, Nrf2, and Cytokeratin 18 in Patients with Hashimoto's Disease. SISLI ETFAL HASTANESI TIP BULTENI 2023; 57:473-478. [PMID: 38268661 PMCID: PMC10805046 DOI: 10.14744/semb.2023.95826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 07/28/2023] [Accepted: 08/09/2023] [Indexed: 01/26/2024]
Abstract
Objectives Fetuin-A is a protein that exhibits proatherogenic, pro-inflammatory, and anti-inflammatory effects with increased insulin resistance and adipocyte dysfunction. The nuclear factor erythroid 2-related factor (Nrf2) is a transcription factor that is crucial for protecting cells against oxidative damage. As a cell death product, cytokeratin 18 (CK18) levels increase during necrosis and apoptosis of both normal and tumor cells. We analyzed the plasma levels of three biomarkers based on the hypothesis that they might be related to some pathophysiological pathways in Hashimoto's disease. Methods We compared 34 female patients with overt hypothyroidism due to Hashimoto's disease (Group 1) with 34 age-matched healthy females (Group 2). For comparison, plasma levels of thyroid-stimulating hormone (TSH), fetuin-A, Nrf2, and CK18 were measured in all participants. Results In group 1, the mean TSH levels (31.4±15.3) were significantly higher than those in group 2 (2.6±1.0) (p<0.001). The levels of mean fetuin-A (606.7±34.2) and Nrf2 (1.3±0.6) were found to be significantly higher in group 1 than in group 2 (440.0±34.2 vs. 0.7±0.2) (p<0.001 for both). CK18 levels in group 1 (0.36±0.13) were also significantly higher than in group 2 (0.26±0.16) (p=0.020). A significant correlation was observed between TSH levels and fetuin-A (r=0.401, p=0.001). Conclusion Increased levels of fetuin-A, Nrf2, and CK18 may be a consequence or cause of the pathophysiological pathways of Hashimoto's disease. The clinical significance of increased levels of these biomarkers requires further investigation.
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Affiliation(s)
- Esma Yetim
- Department of Internal Medicine, Harran University Faculty of Medicine, Sanliurfa, Türkiye
| | - Mehmet Ali Eren
- Department of Endocrinology, Harran University, Faculty of Medicine, Sanliurfa, Türkiye
| | - Huseyin Karaaslan
- Department of Endocrinology, Harran University, Faculty of Medicine, Sanliurfa, Türkiye
| | - Tevfik Sabuncu
- Department of Endocrinology, Harran University, Faculty of Medicine, Sanliurfa, Türkiye
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Perpiñán E, Sanchez-Fueyo A, Safinia N. Immunoregulation: the interplay between metabolism and redox homeostasis. FRONTIERS IN TRANSPLANTATION 2023; 2:1283275. [PMID: 38993920 PMCID: PMC11235320 DOI: 10.3389/frtra.2023.1283275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Accepted: 11/13/2023] [Indexed: 07/13/2024]
Abstract
Regulatory T cells are fundamental for the induction and maintenance of immune homeostasis, with their dysfunction resulting in uncontrolled immune responses and tissue destruction predisposing to autoimmunity, transplant rejection and several inflammatory and metabolic disorders. Recent discoveries have demonstrated that metabolic processes and mitochondrial function are critical for the appropriate functioning of these cells in health, with their metabolic adaptation, influenced by microenvironmental factors, seen in several pathological processes. Upon activation regulatory T cells rearrange their oxidation-reduction (redox) system, which in turn supports their metabolic reprogramming, adding a layer of complexity to our understanding of cellular metabolism. Here we review the literature surrounding redox homeostasis and metabolism of regulatory T cells to highlight new mechanistic insights of these interlinked pathways in immune regulation.
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Affiliation(s)
| | | | - N. Safinia
- Department of Inflammation Biology, School of Immunology and Microbial Sciences, Institute of Liver Studies, James Black Centre, King’s College London, London, United Kingdom
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Lee S, Ma X, Lee W. Association between exposure to external airborne agents and autoimmune disease. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2023; 263:115334. [PMID: 37567098 DOI: 10.1016/j.ecoenv.2023.115334] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Revised: 08/02/2023] [Accepted: 08/03/2023] [Indexed: 08/13/2023]
Abstract
The etiology of autoimmune disease pathogeneses remains obscure, and the impact of general environmental or occupational exposure to external airborne agents (EAA) on autoimmune diseases remains understudied. This study was conducted to elucidate the association between exposure to EAA and the risk of autoimmune diseases according to exposure type. From the NHIS-NSC (2002-2019), 17,984,963 person-years were included in the data analysis. Autoimmune diseases were categorized based on the InterLymph classification. We estimated the incidence and rate ratio of autoimmune diseases according to the EAA exposure. Association between exposure and autoimmune diseases was investigated using logistic regression analysis, adjusted for potential confounders. Of the 1,082,879 participants, 86,376 (8.0%) were diagnosed with autoimmune diseases. Among these, 208 (14.1%) experienced severe exposure to EAA. Total EAA exposure was significantly associated with any autoimmune disease (OR: 1.29, 95% CI: 1.11-1.49) and organ-specific diseases (OR: 1.28, 95% CI: 1.08-1.53). Inorganic dust exposure was associated with organ-specific diseases (OR, 1.38; 95% CI: 1.01-1.81). Exposure to other dust was significantly associated with any autoimmune disease (OR: 1.35, 95% CI: 1.10-1.66), connective tissue diseases (OR: 1.43, 95% CI: 1.03-1.99), and organ-specific diseases (OR: 1.28, 95% CI: 1.00-1.65). Exposure to EAA was predominantly related to psoriasis, rheumatoid arthritis (RA), and type 1 diabetes (T1DM). We found that exposure to EAA is a potential risk factor for autoimmune diseases, especially psoriasis, RA, and T1DM. Our findings provide insight into the role of exposure to severe airborne agents in the pathogenesis of autoimmune diseases.
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Affiliation(s)
- Seunghyun Lee
- Department of Occupational and Environmental Medicine, College of Medicine, Gachon University, Incheon, Republic of Korea
| | - Xiaoxue Ma
- Department of Pediatrics, The First Hospital of China Medical University, Shenyang, China
| | - Wanhyung Lee
- Department of Preventive Medicine, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.
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Kravchenko V, Zakharchenko T. Thyroid hormones and minerals in immunocorrection of disorders in autoimmune thyroid diseases. Front Endocrinol (Lausanne) 2023; 14:1225494. [PMID: 37711890 PMCID: PMC10499380 DOI: 10.3389/fendo.2023.1225494] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 08/08/2023] [Indexed: 09/16/2023] Open
Abstract
Thyroid hormones and essential elements iodine (I), selenium (Se), iron (Fe), copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), etc. play an important role in the work of many organs and systems of the body, including the immune system and the thyroid gland, and a violation of their supply can be the cause of pathological changes in them. In pathology, the interaction between thyroid hormones (TG), minerals and the immune system is disturbed. The review of the literature examines the immunomodulatory role of TG, minerals, their properties, and their participation in the pathogenesis of autoimmune thyroid diseases (AITD). The study of the relationship between the excess or deficiency of minerals and AITD is described. The basis of the development of AITD - Hashimoto's thyroiditis (HT), Graves' disease (GD), Graves' ophthalmopathy (GO) is the loss of immune tolerance to thyroid antigens - thyroid peroxidase (TPO), thyroglobulin (Tg) and thyroid-stimulating hormone receptor (TSH-R). Immune-mediated mechanisms - production of autoantibodies to thyroid antigens and lymphocytic thyroid infiltration - are involved in the pathogenesis of AITD. Insufficiency of regulatory T cells (Treg) and regulatory B cells (Breg), imbalance between Th17-lymphocytes and Treg-lymphocytes, abnormal production of pro-inflammatory cytokines has a significant influence on the progression of AITD. With AITD, the balance between oxidants and antioxidants is disturbed and oxidative stress (OS) occurs. The lack of modern effective pharmacological therapy of AITD prompted us to consider the mechanisms of influence, possibilities of immunocorrection of pathogenetic factors using TG, micro/macronutrients. In order to develop a more effective treatment strategy, as well as approaches to prevention, a critical analysis of the ways of immunotherapeutic use of dietary supplements of I, Se, Zn, Mg and other minerals in AITD was carried out.
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Affiliation(s)
- Viktor Kravchenko
- Epidemiology of Endocrine Diseases, Vasily Pavlovich Komisarenko Institute of Endocrinology and Metabolism, Kyiv, Ukraine
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Zirilli A, Ruggeri RM, Barbalace MC, Hrelia S, Giovanella L, Campennì A, Cannavò S, Alibrandi A. The Influence of Food Regimes on Oxidative Stress: A Permutation-Based Approach Using the NPC Test. Healthcare (Basel) 2023; 11:2263. [PMID: 37628461 PMCID: PMC10454221 DOI: 10.3390/healthcare11162263] [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: 06/28/2023] [Revised: 08/01/2023] [Accepted: 08/06/2023] [Indexed: 08/27/2023] Open
Abstract
(1) Background: This paper aims to assess the existence of significant differences between two dietary regimes (omnivorous vs. semi-vegetarian) with reference to some oxidative stress markers (SOD, GPx, TRxR, GR, AGEs, and AOPPs) using non-parametric combination methodology based on a permutation test. (2) Methods: At the endocrinology unit of Messina University Hospital, two hundred subjects were asked to fill out a questionnaire about their dietary habits. None were under any pharmacological treatment. Using the NPC test, all comparisons were performed stratifying patients according to gender, age (≤40 or >40 years), BMI (normal weight vs. overweight), physical activity (sedentary vs. active lifestyle), TSH, FT4 levels in quartiles, and diagnosis of Hashimoto's thyroiditis. We evaluated differences in oxidative stress parameters in relation to two examined dietary regimes (omnivorous vs. semi-vegetarian). (3) Results: The antioxidant parameters GPx and TRxR were significantly lower in subjects with an omnivorous diet than in semi-vegetarians, particularly in females, both age groups, subjects with normal weight, those not affected by Hashimoto's thyroiditis, and both the sedentary and active lifestyle groups. Finally, the AGE and AOPP markers were significantly lower in semi-vegetarians. (4) Conclusion: Thanks to the NPC methodology, we can state that dietary patterns exert a significant influence on some oxidative stress parameters.
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Affiliation(s)
- Agata Zirilli
- Department of Economics, University of Messina, 98122 Messina, Italy;
| | - Rosaria Maddalena Ruggeri
- Department of Human Pathology of Adults and Developmental Age “G. Barresi”, University of Messina, 98125 Messina, Italy; (R.M.R.); (S.C.)
| | - Maria Cristina Barbalace
- Department for Life Quality Studies, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; (M.C.B.); (S.H.)
| | - Silvana Hrelia
- Department for Life Quality Studies, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; (M.C.B.); (S.H.)
| | - Luca Giovanella
- Clinic for Nuclear Medicine and Molecular Imaging, Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland;
- Clinic for Nuclear Medicine, University Hospital of Zürich, 8091 Zürich, Switzerland
| | - Alfredo Campennì
- Unit of Nuclear Medicine, Department of Biomedical Sciences and Morphological and Functional Images, University of Messina, 98125 Messina, Italy;
| | - Salvatore Cannavò
- Department of Human Pathology of Adults and Developmental Age “G. Barresi”, University of Messina, 98125 Messina, Italy; (R.M.R.); (S.C.)
| | - Angela Alibrandi
- Department of Economics, University of Messina, 98122 Messina, Italy;
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Gałuszka-Bulaga A, Tkacz K, Węglarczyk K, Siedlar M, Baran J. Air pollution induces pyroptosis of human monocytes through activation of inflammasomes and Caspase-3-dependent pathways. J Inflamm (Lond) 2023; 20:26. [PMID: 37563611 PMCID: PMC10416410 DOI: 10.1186/s12950-023-00353-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 07/17/2023] [Indexed: 08/12/2023] Open
Abstract
According to the World Health Organization (WHO), air pollution is one of the most serious threats for our planet. Despite a growing public awareness of the harmful effects of air pollution on human health, the specific influence of particulate matter (PM) on human immune cells remains poorly understood. In this study, we investigated the effect of PM on peripheral blood monocytes in vitro. Monocytes from healthy donors (HD) were exposed to two types of PM: NIST (SRM 1648a, standard urban particulate matter from the US National Institute for Standards and Technology) and LAP (SRM 1648a with the organic fraction removed). The exposure to PM-induced mitochondrial ROS production followed by the decrease of mitochondrial membrane potential and activation of apoptotic protease activating factor 1 (Apaf-1), Caspase-9, and Caspase-3, leading to the cleavage of Gasdermin E (GSDME), and initiation of pyroptosis. Further analysis showed a simultaneous PM-dependent activation of inflammasomes, including NLRP3 (nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3) and Caspase-1, followed by cleavage of Gasdermin D (GSDMD) and secretion of IL-1β. These observations suggest that PM-treated monocytes die by pyroptosis activated by two parallel signaling pathways, related to the inorganic and organic PM components. The release of IL-1β and expression of danger-associated molecular patterns (DAMPs) by pyroptotic cells further activated the remnant viable monocytes to produce inflammatory cytokines (TNF-α, IL-6, IL-8) and protected them from death induced by the second challenge with PM.In summary, our report shows that PM exposure significantly impacts monocyte function and induces their death by pyroptosis. Our observations indicate that the composition of PM plays a crucial role in this process-the inorganic fraction of PM is responsible for the induction of the Caspase-3-dependent pyroptotic pathway. At the same time, the canonical inflammasome path is activated by the organic components of PM, including LPS (Lipopolysaccharide/endotoxin). PM-induced pyroptosis of human monocytes. Particulate matter (PM) treatment affects monocytes viability already after 15 min of their exposure to NIST or LAP in vitro. The remnant viable monocytes in response to danger-associated molecular patterns (DAMPs) release pro-inflammatory cytokines and activate Th1 and Th17 cells. The mechanism of PM-induced cell death includes the increase of reactive oxygen species (ROS) production followed by collapse of mitochondrial membrane potential (ΔΨm), activation of Apaf-1, Caspase-9 and Caspase-3, leading to activation of Caspase-3-dependent pyroptotic pathway, where Caspase-3 cleaves Gasdermin E (GSDME) to produce a N-terminal fragment responsible for the switch from apoptosis to pyroptosis. At the same time, PM activates the canonical inflammasome pathway, where activated Caspase-1 cleaves the cytosolic Gasdermin D (GSDMD) to produce N-terminal domain allowing IL-1β secretion. As a result, PM-treated monocytes die by pyroptosis activated by two parallel pathways-Caspase-3-dependent pathway related to the inorganic fraction of PM and the canonical inflammasome pathway dependent on the organic components of PM.
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Affiliation(s)
- Adrianna Gałuszka-Bulaga
- Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, Wielicka Street 265, 30-663 Krakow, Poland
| | - Karolina Tkacz
- Department of Clinical Immunology, University Children’s Hospital, Krakow, Poland
| | - Kazimierz Węglarczyk
- Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, Wielicka Street 265, 30-663 Krakow, Poland
- Department of Clinical Immunology, University Children’s Hospital, Krakow, Poland
| | - Maciej Siedlar
- Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, Wielicka Street 265, 30-663 Krakow, Poland
- Department of Clinical Immunology, University Children’s Hospital, Krakow, Poland
| | - Jarek Baran
- Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, Wielicka Street 265, 30-663 Krakow, Poland
- Department of Clinical Immunology, University Children’s Hospital, Krakow, Poland
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21
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Taherinia S, Heidari Z, Salehidoost R, Karimifar M, Arab A, Alshahrani SH, Askari G. Associations between empirically derived dietary patterns and oxidative stress and inflammation in adults with primary hypothyroidism: a case-control study. BMC Endocr Disord 2023; 23:105. [PMID: 37161471 PMCID: PMC10170704 DOI: 10.1186/s12902-023-01348-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Accepted: 04/19/2023] [Indexed: 05/11/2023] Open
Abstract
BACKGROUND Primary hypothyroidism is a common endocrine disorder caused by impaired production of thyroid hormones. Recent studies have shown that dietary habits, oxidative stress, and inflammation may play roles in thyroid hypofunction. Thus, the present article aimed to determine the relationship between major dietary patterns and oxidative stress and inflammation in primary hypothyroid patients and healthy people in Iranian adults. METHODS This matched case-control study was conducted on 200 participants (100 cases and 100 controls). The presence of primary hypothyroidism was determined by endocrinologists based on American Thyroid Association (ATA) criteria. Dietary intake was assessed using a validated 168-item, semi-quantitative food frequency questionnaire (FFQ). The principal component analysis (PCA) method was used to derive major dietary patterns. Statistical analysis was performed using logistic regression analysis, and the findings were reported using odds ratios (ORs) with 95% CIs. RESULTS We identified 2 major dietary patterns (i.e., healthy and Western dietary patterns). After adjusting for confounding variables, participants in the highest tertile of the healthy eating pattern had lower odds of primary hypothyroidism. Also, there was a significant relationship between total antioxidant capacity (TAC) levels and thyroid hypofunction; however, no significant correlation was seen between the Western dietary pattern and malondialdehyde (MDA) and C-reactive protein (CRP) with hypothyroidism. CONCLUSIONS There were statistically direct associations between healthy dietary patterns (loaded with vegetables, nuts and seeds, fruits, dried fruits, olives, garlic, black pepper, starchy vegetables, low-fat dairy, and legumes) and increased TAC levels with a decreased risk of thyroid hypofunction. However, Western dietary patterns and MDA and CRP levels did not associate with an underactive thyroid.
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Affiliation(s)
- Sorour Taherinia
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
- Department of Community Nutrition, School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Zahra Heidari
- Department of Biostatistics and Epidemiology, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Rezvan Salehidoost
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mozhgan Karimifar
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Arman Arab
- Department of Community Nutrition, School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Gholamreza Askari
- Department of Community Nutrition, School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
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22
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Lessons Learned from Anatomic Susceptibility in Vitiligo Patients: A Systematic Review. CURRENT DERMATOLOGY REPORTS 2023. [DOI: 10.1007/s13671-023-00384-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2023]
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23
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Maleki H, Azadi H, Yousefpoor Y, Doostan M, Doostan M, Farzaei MH. Encapsulation of Ginger Extract in Nanoemulsions: Preparation, Characterization and in vivo Evaluation in Rheumatoid Arthritis. J Pharm Sci 2023; 112:1687-1697. [PMID: 36773928 DOI: 10.1016/j.xphs.2023.02.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 02/01/2023] [Accepted: 02/01/2023] [Indexed: 02/11/2023]
Abstract
Ginger is an anti-inflammatory and antioxidant natural substance, however, its effectiveness is limited primarily due to insufficient solubility and low oral bioavailability. This study aimed to formulate ginger extract into nanoemulsion (NE) to enhance therapeutic benefits against rheumatoid arthritis (RA). Hence, ginger extract-loaded NEs were prepared by the spontaneous emulsification method. The NE that passed the thermodynamic stability analyses showed no phase changes or appearance of turbidity. They had an average droplet diameter of 76 ± 45 nm with a zeta potential of - 35 ± 12 mV. Besides, the high antioxidant activities (IC50 = 53.89 µg/mL), about ten times increment of the skin permeability, and no sign of skin irritancy were observed from the ginger-loaded NE. The anti-arthritic evaluations of RA-induced rats treated with ginger-loaded NE showed a significant decline in arthritic symptoms and the highest rate of paw edema inhibition (27.7 %). In addition, the level of involved inflammatory cytokines in the serum of rats was significantly reduced (p < 0.05) compared to the negative control, so that histopathological manifestations also approved the reduction of inflammation indications. Thus, the topical delivery of ginger-loaded NE can be an efficient approach for reducing inflammation and inhibit of RA symptoms.
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Affiliation(s)
- Hassan Maleki
- Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; Pharmaceutical Sciences Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
| | - Hediyeh Azadi
- Pharmaceutical Sciences Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Yaser Yousefpoor
- Research Center of Advanced Technologies in Medicine, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran; Khalil Abad Health Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahtab Doostan
- Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Maryam Doostan
- Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mohammad Hosein Farzaei
- Pharmaceutical Sciences Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
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24
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Zhan Q, Zhang J, Lin Y, Chen W, Fan X, Zhang D. Pathogenesis and treatment of Sjogren's syndrome: Review and update. Front Immunol 2023; 14:1127417. [PMID: 36817420 PMCID: PMC9932901 DOI: 10.3389/fimmu.2023.1127417] [Citation(s) in RCA: 68] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 01/23/2023] [Indexed: 02/05/2023] Open
Abstract
Sjogren's syndrome (SS) is a chronic autoimmune disease accompanied by multiple lesions. The main manifestations include dryness of the mouth and eyes, along with systemic complications (e.g., pulmonary disease, kidney injury, and lymphoma). In this review, we highlight that IFNs, Th17 cell-related cytokines (IL-17 and IL-23), and B cell-related cytokines (TNF and BAFF) are crucial for the pathogenesis of SS. We also summarize the advances in experimental treatment strategies, including targeting Treg/Th17, mesenchymal stem cell treatment, targeting BAFF, inhibiting JAK pathway, et al. Similar to that of SLE, RA, and MS, biotherapeutic strategies of SS consist of neutralizing antibodies and inflammation-related receptor blockers targeting proinflammatory signaling pathways. However, clinical research on SS therapy is comparatively rare. Moreover, the differences in the curative effects of immunotherapies among SS and other autoimmune diseases are not fully understood. We emphasize that targeted drugs, low-side-effect drugs, and combination therapies should be the focus of future research.
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Affiliation(s)
| | | | | | | | | | - Dunfang Zhang
- State Key Laboratory of Biotherapy and Cancer Center, Department of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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25
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Di Salvo E, Casciaro M, Giorgianni CM, Cicero N, Gangemi S. Age-Related Diseases and Foods Generating Chlorinative Stress. Antioxidants (Basel) 2023; 12:antiox12020249. [PMID: 36829808 PMCID: PMC9952263 DOI: 10.3390/antiox12020249] [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: 11/16/2022] [Revised: 01/08/2023] [Accepted: 01/20/2023] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND Aging is a slow and inexorable process affecting all life beings and is characterised by age-related worsening in adaptation to external changes. Several factors contribute to such a process, and oxidative stress due to external damages is one key player. Of particular interest is the oxidative stress generated from halogen compounds such as chloride. Hypochlorus acid is produced starting from MPO's interaction with hydrogen peroxide. We focused on the oxidation of tyrosine residues by HOCl, which leads as a result to the formation of 3-chlorotyrosine (3-ClTyr). This molecule, due to its stability, is considered a marker for MPO activity. RESULTS We collected data from literature research articles evaluating chlorinative stress and the effects of 3-ClTyr on chronic diseases linked to aging. As diseases are not the only source of 3-ClTyr in people, we also focused on other origins of chlorinative stress, such as food intake. DISCUSSION Oxidation and halogenation are caused by infectious diseases and by pathologies characterised by inflammation. Moreover, diet could negatively or positively influence chlorinative stress. Comparing 3-ClTyr levels in the oldest and youngest old with age-related diseases and comparing data between different geographic areas with different pesticide rules could be the next challenge.
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Affiliation(s)
- Eleonora Di Salvo
- Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy
| | - Marco Casciaro
- School and Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy
- Correspondence: ; Tel.: +39-0902212013
| | - Concetto Mario Giorgianni
- Department of Biomedical, Dental and Morphological and Functional Imaging, University of Messina, 98125 Messina, Italy
| | - Nicola Cicero
- Department of Biomedical, Dental and Morphological and Functional Imaging, University of Messina, 98125 Messina, Italy
- Science4life srl, Spin off Company, University of Messina, 98100 Messina, Italy
| | - Sebastiano Gangemi
- School and Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy
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26
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Burke ND, Nixon B, Roman SD, Schjenken JE, Walters JLH, Aitken RJ, Bromfield EG. Male infertility and somatic health - insights into lipid damage as a mechanistic link. Nat Rev Urol 2022; 19:727-750. [PMID: 36100661 DOI: 10.1038/s41585-022-00640-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/27/2022] [Indexed: 11/08/2022]
Abstract
Over the past decade, mounting evidence has shown an alarming association between male subfertility and poor somatic health, with substantial evidence supporting the increased incidence of oncological disease, cardiovascular disease, metabolic disorders and autoimmune diseases in men who have previously received a subfertility diagnosis. This paradigm is concerning, but might also provide a novel window for a crucial health reform in which the infertile phenotype could serve as an indication of potential pathological conditions. One of the major limiting factors in this association is the poor understanding of the molecular features that link infertility with comorbidities across the life course. Enzymes involved in the lipid oxidation process might provide novel clues to reconcile the mechanistic basis of infertility with incident pathological conditions. Building research capacity in this area is essential to enhance the early detection of disease states and provide crucial information about the disease risk of offspring conceived through assisted reproduction.
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Affiliation(s)
- Nathan D Burke
- Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, Callaghan, New South Wales, Australia
- Hunter Medical Research Institute, Infertility and Reproduction Research Program, New Lambton Heights, New South Wales, Australia
| | - Brett Nixon
- Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, Callaghan, New South Wales, Australia
- Hunter Medical Research Institute, Infertility and Reproduction Research Program, New Lambton Heights, New South Wales, Australia
| | - Shaun D Roman
- Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, Callaghan, New South Wales, Australia
- Hunter Medical Research Institute, Infertility and Reproduction Research Program, New Lambton Heights, New South Wales, Australia
- Priority Research Centre for Drug Development, School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, Callaghan, New South Wales, Australia
| | - John E Schjenken
- Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, Callaghan, New South Wales, Australia
- Hunter Medical Research Institute, Infertility and Reproduction Research Program, New Lambton Heights, New South Wales, Australia
| | - Jessica L H Walters
- Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, Callaghan, New South Wales, Australia
- Hunter Medical Research Institute, Infertility and Reproduction Research Program, New Lambton Heights, New South Wales, Australia
| | - R John Aitken
- Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, Callaghan, New South Wales, Australia
- Hunter Medical Research Institute, Infertility and Reproduction Research Program, New Lambton Heights, New South Wales, Australia
| | - Elizabeth G Bromfield
- Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, Callaghan, New South Wales, Australia.
- Hunter Medical Research Institute, Infertility and Reproduction Research Program, New Lambton Heights, New South Wales, Australia.
- Department of Biomolecular Health Sciences, Utrecht University, Utrecht, Netherlands.
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27
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Chen C, Wang P, Zhang RD, Fang Y, Jiang LQ, Fang X, Zhao Y, Wang DG, Ni J, Pan HF. Mendelian randomization as a tool to gain insights into the mosaic causes of autoimmune diseases. Clin Exp Rheumatol 2022; 21:103210. [PMID: 36273526 DOI: 10.1016/j.autrev.2022.103210] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Revised: 10/06/2022] [Accepted: 10/11/2022] [Indexed: 12/14/2022]
Abstract
Autoimmune diseases (ADs) are a broad range of disorders which are characterized by long-term inflammation and tissue damage arising from an immune response against one's own tissues. It is now widely accepted that the causes of ADs include environmental factors, genetic susceptibility and immune dysregulation. However, the exact etiology of ADs has not been fully elucidated to date. Because observational studies are plagued by confounding factors and reverse causality, no firm conclusions can be drawn about the etiology of ADs. Over the years, Mendelian randomization (MR) analysis has come into focus, offering unique perspectives and insights into the etiology of ADs and promising the discovery of potential therapeutic interventions. In MR analysis, genetic variation (alleles are randomly dispensed during meiosis, usually irrespective of environmental or lifestyle factors) is used instead of modifiable exposure to explore the link between exposure factors and disease or other outcomes. Therefore, MR analysis can provide a valuable method for exploring the causal relationship between different risk factors and ADs when its inherent assumptions and limitations are fully considered. This review summarized the recent findings of MR in major ADs, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), and type 1 diabetes mellitus (T1DM), focused on the effects of different risk factors on ADs risks. In addition, we also discussed the opportunities and challenges of MR methods in ADs research.
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Affiliation(s)
- Cong Chen
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui, China; Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, China
| | - Peng Wang
- Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, China; Teaching Center for Preventive Medicine, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui, China
| | - Ruo-Di Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui, China; Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, China
| | - Yang Fang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui, China; Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, China
| | - Ling-Qiong Jiang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui, China; Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, China
| | - Xi Fang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui, China; Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, China
| | - Yan Zhao
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui, China; Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, China
| | - De-Guang Wang
- Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, China; Department of Nephrology, The Second Hospital of Anhui Medical University, Hefei, China.
| | - Jing Ni
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui, China; Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, China.
| | - Hai-Feng Pan
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui, China; Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, China.
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28
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Sex Biases in Cancer and Autoimmune Disease Incidence Are Strongly Positively Correlated with Mitochondrial Gene Expression across Human Tissues. Cancers (Basel) 2022; 14:cancers14235885. [PMID: 36497367 PMCID: PMC9736300 DOI: 10.3390/cancers14235885] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 11/10/2022] [Accepted: 11/24/2022] [Indexed: 12/02/2022] Open
Abstract
Cancer occurs more frequently in men while autoimmune diseases (AIDs) occur more frequently in women. To explore whether these sex biases have a common basis, we collected 167 AID incidence studies from many countries for tissues that have both a cancer type and an AID that arise from that tissue. Analyzing a total of 182 country-specific, tissue-matched cancer-AID incidence rate sex bias data pairs, we find that, indeed, the sex biases observed in the incidence of AIDs and cancers that occur in the same tissue are positively correlated across human tissues. The common key factor whose levels across human tissues are most strongly associated with these incidence rate sex biases is the sex bias in the expression of the 37 genes encoded in the mitochondrial genome.
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29
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Asgari R, Yarani R, Mohammadi P, Emami Aleagha MS. HIF-1α in the Crosstalk Between Reactive Oxygen Species and Autophagy Process: A Review in Multiple Sclerosis. Cell Mol Neurobiol 2022; 42:2121-2129. [PMID: 34089426 PMCID: PMC11421632 DOI: 10.1007/s10571-021-01111-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 05/27/2021] [Indexed: 12/16/2022]
Abstract
Cellular stress can lead to the production of reactive oxygen species (ROS) while autophagy, as a catabolic pathway, protects the cells against stress. Autophagy in its turn plays a pivotal role in the pathophysiology of multiple sclerosis (MS). In the current review, we first summarized the contribution of ROS and autophagy to MS pathogenesis. Then probable crosstalk between these two pathways through HIF-1α for the first time has been proposed with the hope of employing a better understanding of MS pathophysiology and probable therapeutic approaches.
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Affiliation(s)
- Rezvan Asgari
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Reza Yarani
- Translational Type 1 Diabetes Biology, Department of Clinical Research, Steno Diabetes Center Copenhagen, Copenhagen, Denmark
| | - Pantea Mohammadi
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
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30
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Yu X, Cui Y, Zhu X, Xu H, Li L, Gao G. MicroRNAs: Emerging players in the pathogenesis of vitiligo. Front Cell Dev Biol 2022; 10:964982. [PMID: 36187493 PMCID: PMC9523438 DOI: 10.3389/fcell.2022.964982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 08/03/2022] [Indexed: 11/13/2022] Open
Abstract
Vitiligo is an autoimmune skin disease characterized by presence of pale patchy areas of depigmentation. MicroRNAs (miRNAs) are important regulators of gene expression and play significant roles in diverse biological and pathological processes. Accumulating evidence has shown that miRNAs were differentially expressed in skin lesions and peripheral blood mononuclear cells of patients with vitiligo. In particular, miRNAs are significantly correlated with the development and progression of vitiligo. The abundance of some miRNAs in serum was also correlated with the vitiligo lesion severity, indicating that miRNAs might serve as prognostic biomarkers. Importantly, the direct involvement of miRNAs in the pathogenesis of vitiligo has been demonstrated. For example, increased expression of miR-25 contributes to vitiligo through promoting the dysfunction and oxidative stress-induced destruction of melanocytes. However, there are limited studies on the function and mechanism of deregulated miRNAs in vitiligo. Further studies are required to establish clinical applications of miRNAs for vitiligo. More in-depth investigations of miRNAs are needed for the understanding of the pathogenesis of vitiligo and the development of novel therapeutic targets. This present review summarizes the current literature on the deregulation and pathogenic roles of miRNAs in vitiligo. We also highlight the potential clinical applications of miRNAs in patients with vitiligo.
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Affiliation(s)
| | | | | | | | - Linfeng Li
- *Correspondence: Linfeng Li, ; Guangcheng Gao,
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Inhibiting peripheral and central MAO-B ameliorates joint inflammation and cognitive impairment in rheumatoid arthritis. EXPERIMENTAL & MOLECULAR MEDICINE 2022; 54:1188-1200. [PMID: 35982301 PMCID: PMC9440195 DOI: 10.1038/s12276-022-00830-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 05/07/2022] [Accepted: 05/31/2022] [Indexed: 12/29/2022]
Abstract
Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation and the destruction of joints and systemic organs. RA is commonly accompanied by neuropsychiatric complications, such as cognitive impairment and depression. However, the role of monoamine oxidase (MAO) and its inhibitors in controlling neurotransmitters associated with these complications in RA have not been clearly identified. Here, we report that peripheral and central MAO-B are highly associated with joint inflammation and cognitive impairment in RA, respectively. Ribonucleic acid (RNA) sequencing and protein expression quantification were used to show that MAO-B and related molecules, such as gamma aminobutyric acid (GABA), were elevated in the inflamed synovium of RA patients. In primary cultured fibroblast-like synoviocytes in the RA synovium, MAO-B expression was significantly increased by tumor necrosis factor (TNF)-α-induced autophagy, which produces putrescine, the polyamine substrate for GABA synthesis. We also observed that MAO-B-mediated aberrant astrocytic production of GABA was augmented by interleukin (IL)-1β and inhibited CA1-hippocampal pyramidal neurons, which are responsible for memory storage, in an animal model of RA. Moreover, a newly developed reversible inhibitor of MAO-B ameliorated joint inflammation by inhibiting cyclooxygenase (Cox)-2. Therefore, MAO-B can be an effective therapeutic target for joint inflammation and cognitive impairment in patients with RA. Inhibiting an enzyme that is upregulated during joint inflammation may prove a valuable therapy for rheumatoid arthritis (RA). As well as causing considerable pain and discomfort in the joints, RA can also trigger neuropsychiatric problems including depression and memory impairment. The monoamine oxidase (MAO) enzyme family is involved in the control of neurotransmitters, and there is evidence that links MAO-B levels with systemic inflammation. C. Justin Lee at Center for Cognition and Sociality, Institute for Basic Science,, Daejeon, South Korea, and co-workers examined the role of MAO-B in RA using patient tissue samples and mouse models. MAO-B and related molecules were upregulated in patients’ inflamed joint tissues. In mice, elevated MAO-B triggered the inhibition of nerve cell activity related to memory storage. A novel drug that inhibits MAO-B reduced RA-related inflammation and cognitive impairment in mice, suggesting a promising approach to treatment.
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Ogbodo JO, Arazu AV, Iguh TC, Onwodi NJ, Ezike TC. Volatile organic compounds: A proinflammatory activator in autoimmune diseases. Front Immunol 2022; 13:928379. [PMID: 35967306 PMCID: PMC9373925 DOI: 10.3389/fimmu.2022.928379] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 06/30/2022] [Indexed: 11/13/2022] Open
Abstract
The etiopathogenesis of inflammatory and autoimmune diseases, including pulmonary disease, atherosclerosis, and rheumatoid arthritis, has been linked to human exposure to volatile organic compounds (VOC) present in the environment. Chronic inflammation due to immune breakdown and malfunctioning of the immune system has been projected to play a major role in the initiation and progression of autoimmune disorders. Macrophages, major phagocytes involved in the regulation of chronic inflammation, are a major target of VOC. Excessive and prolonged activation of immune cells (T and B lymphocytes) and overexpression of the master pro-inflammatory constituents [cytokine and tumor necrosis factor-alpha, together with other mediators (interleukin-6, interleukin-1, and interferon-gamma)] have been shown to play a central role in the pathogenesis of autoimmune inflammatory responses. The function and efficiency of the immune system resulting in immunostimulation and immunosuppression are a result of exogenous and endogenous factors. An autoimmune disorder is a by-product of the overproduction of these inflammatory mediators. Additionally, an excess of these toxicants helps in promoting autoimmunity through alterations in DNA methylation in CD4 T cells. The purpose of this review is to shed light on the possible role of VOC exposure in the onset and progression of autoimmune diseases.
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Affiliation(s)
- John Onyebuchi Ogbodo
- Department of Science Laboratory Technology, University of Nigeria, Nsukkagu, Enugu State, Nigeria
| | - Amarachukwu Vivan Arazu
- Department of Science Laboratory Technology, University of Nigeria, Nsukkagu, Enugu State, Nigeria
| | - Tochukwu Chisom Iguh
- Department of Plant Science and Biotechnology, University of Nigeria, Nsukka, Enugu State, Nigeria
| | - Ngozichukwuka Julie Onwodi
- Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria, Nsukka, Enugu State, Nigeria
| | - Tobechukwu Christian Ezike
- Department of Biochemistry, University of Nigeria, Nsukka, Enugu State, Nigeria
- *Correspondence: Tobechukwu Christian Ezike,
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Arleevskaya M, Takha E, Petrov S, Kazarian G, Renaudineau Y, Brooks W, Larionova R, Korovina M, Valeeva A, Shuralev E, Mukminov M, Kravtsova O, Novikov A. Interplay of Environmental, Individual and Genetic Factors in Rheumatoid Arthritis Provocation. Int J Mol Sci 2022; 23:ijms23158140. [PMID: 35897715 PMCID: PMC9329780 DOI: 10.3390/ijms23158140] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 07/18/2022] [Accepted: 07/19/2022] [Indexed: 02/05/2023] Open
Abstract
In this review, we explore systemization of knowledge about the triggering effects of non-genetic factors in pathogenic mechanisms that contribute to the development of rheumatoid arthritis (RA). Possible mechanisms involving environmental and individual factors in RA pathogenesis were analyzed, namely, infections, mental stress, sleep deprivation ecology, age, perinatal and gender factors, eating habits, obesity and smoking. The non-genetic factors modulate basic processes in the body with the impact of these factors being non-specific, but these common challenges may be decisive for advancement of the disease in the predisposed body at risk for RA. The provocation of this particular disease is associated with the presence of congenital loci minoris resistentia. The more frequent non-genetic factors form tangles of interdependent relationships and, thereby, several interdependent external factors hit one vulnerable basic process at once, either provoking or reinforcing each other. Understanding the specific mechanisms by which environmental and individual factors impact an individual under RA risk in the preclinical stages can contribute to early disease diagnosis and, if the factor is modifiable, might be useful for the prevention or delay of its development.
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Affiliation(s)
- Marina Arleevskaya
- Central Research Laboratory, Kazan State Medical Academy, 420012 Kazan, Russia; (E.T.); (S.P.); (G.K.); (R.L.); (M.K.); (A.V.); (E.S.); (M.M.)
- Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, Russia;
- Correspondence: ; Tel.: +7-89172-886-679; Fax: +7-843-238-5413
| | - Elena Takha
- Central Research Laboratory, Kazan State Medical Academy, 420012 Kazan, Russia; (E.T.); (S.P.); (G.K.); (R.L.); (M.K.); (A.V.); (E.S.); (M.M.)
| | - Sergey Petrov
- Central Research Laboratory, Kazan State Medical Academy, 420012 Kazan, Russia; (E.T.); (S.P.); (G.K.); (R.L.); (M.K.); (A.V.); (E.S.); (M.M.)
- Institute of Environmental Sciences, Kazan (Volga Region) Federal University, 420008 Kazan, Russia
| | - Gevorg Kazarian
- Central Research Laboratory, Kazan State Medical Academy, 420012 Kazan, Russia; (E.T.); (S.P.); (G.K.); (R.L.); (M.K.); (A.V.); (E.S.); (M.M.)
| | - Yves Renaudineau
- Department of Immunology, CHU Toulouse, INSERM U1291, CNRS U5051, University Toulouse IIII, 31000 Toulouse, France;
| | - Wesley Brooks
- Department of Chemistry, University of South Florida, Tampa, FL 33620, USA;
| | - Regina Larionova
- Central Research Laboratory, Kazan State Medical Academy, 420012 Kazan, Russia; (E.T.); (S.P.); (G.K.); (R.L.); (M.K.); (A.V.); (E.S.); (M.M.)
| | - Marina Korovina
- Central Research Laboratory, Kazan State Medical Academy, 420012 Kazan, Russia; (E.T.); (S.P.); (G.K.); (R.L.); (M.K.); (A.V.); (E.S.); (M.M.)
- Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, Russia;
| | - Anna Valeeva
- Central Research Laboratory, Kazan State Medical Academy, 420012 Kazan, Russia; (E.T.); (S.P.); (G.K.); (R.L.); (M.K.); (A.V.); (E.S.); (M.M.)
| | - Eduard Shuralev
- Central Research Laboratory, Kazan State Medical Academy, 420012 Kazan, Russia; (E.T.); (S.P.); (G.K.); (R.L.); (M.K.); (A.V.); (E.S.); (M.M.)
- Institute of Environmental Sciences, Kazan (Volga Region) Federal University, 420008 Kazan, Russia
| | - Malik Mukminov
- Central Research Laboratory, Kazan State Medical Academy, 420012 Kazan, Russia; (E.T.); (S.P.); (G.K.); (R.L.); (M.K.); (A.V.); (E.S.); (M.M.)
- Institute of Environmental Sciences, Kazan (Volga Region) Federal University, 420008 Kazan, Russia
| | - Olga Kravtsova
- Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, Russia;
| | - Andrey Novikov
- Mathematical Center, Sobolev Instiute of Mathematics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia;
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Jadeja SD, Tobin DJ. Autoantigen Discovery in the Hair Loss Disorder, Alopecia Areata: Implication of Post-Translational Modifications. Front Immunol 2022; 13:890027. [PMID: 35720384 PMCID: PMC9205194 DOI: 10.3389/fimmu.2022.890027] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Accepted: 04/21/2022] [Indexed: 12/24/2022] Open
Abstract
Alopecia areata (AA) is a chronic, multifactorial, polygenic, and heterogeneous disorder affecting growing hair follicles in susceptible individuals, which results in a non-scarring and reversible hair loss with a highly unpredictable course. Despite very considerable research effort, the nature of the precipitating factor(s) responsible for initiating AA in any given hair follicle remains unclear, due largely to significant gaps in our knowledge of the precise sequence of the etiopathogenic events in this dermatosis. However, disease-related changes in the immune-competence of the lower growing hair follicle, together with an active immune response (humoral and cellular) to hair follicle-associated antigens, are key associated phenomena. Confirmation of the hair follicle antigen(s) implicated in AA disease onset has remained stubbornly elusive. While it may be considered somewhat philosophical by some, it is also unclear whether immune-mediated hair loss in AA results from a) an ectopic (i.e., in an abnormal location) immune response to native (unmodified) self-antigens expressed by the healthy hair follicle, b) a normal immune response against modified self-antigens (or neoantigens), or c) a normal immune response against self-antigens (modified/non-modified) that were not previously visible to the immune system (because they were conformationally-hidden or sequestered) but become exposed and presentable in an MHC-I/-II molecule-restricted manner. While some candidate hair follicle antigen target(s) in AA are beginning to emerge, with a potential role for trichohyalin, it is not yet clear whether this represents the initial and immunodominant antigenic focus in AA or is simply one of an expanding repertoire of exposed hair follicle tissue damage-associated antigens that are secondary to the disease. Confirmation of autoantigen identity is essential for our understanding of AA etiopathogenesis, and consequently for developing a more informed therapeutic strategy. Major strides have been made in autoantigen discovery in other autoimmune conditions. In particular, some of these conditions may provide insights into how post-translational modifications (e.g., citrullination, deamidation, etc.) of hair follicle-restricted proteins may increase their antigenicity and so help drive the anti-hair follicle immune attack in AA.
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Affiliation(s)
- Shahnawaz D. Jadeja
- The Charles Institute of Dermatology, School of Medicine, University College Dublin, Dublin, Ireland
| | - Desmond J. Tobin
- The Charles Institute of Dermatology, School of Medicine, University College Dublin, Dublin, Ireland
- The Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland
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Gomes ARQ, Cunha N, Varela ELP, Brígido HPC, Vale VV, Dolabela MF, de Carvalho EP, Percário S. Oxidative Stress in Malaria: Potential Benefits of Antioxidant Therapy. Int J Mol Sci 2022; 23:ijms23115949. [PMID: 35682626 PMCID: PMC9180384 DOI: 10.3390/ijms23115949] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 05/17/2022] [Accepted: 05/19/2022] [Indexed: 01/07/2023] Open
Abstract
Malaria is an infectious disease and a serious public health problem in the world, with 3.3 billion people in endemic areas in 100 countries and about 200 million new cases each year, resulting in almost 1 million deaths in 2018. Although studies look for strategies to eradicate malaria, it is necessary to know more about its pathophysiology to understand the underlying mechanisms involved, particularly the redox balance, to guarantee success in combating this disease. In this review, we addressed the involvement of oxidative stress in malaria and the potential benefits of antioxidant supplementation as an adjuvant antimalarial therapy.
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Affiliation(s)
- Antonio Rafael Quadros Gomes
- Post-Graduate Program in Pharmaceutica Innovation, Institute of Health Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil; (A.R.Q.G.); (H.P.C.B.); (V.V.V.); (M.F.D.)
- Oxidative Stress Research Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil; (N.C.); (E.L.P.V.); (E.P.d.C.)
| | - Natasha Cunha
- Oxidative Stress Research Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil; (N.C.); (E.L.P.V.); (E.P.d.C.)
| | - Everton Luiz Pompeu Varela
- Oxidative Stress Research Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil; (N.C.); (E.L.P.V.); (E.P.d.C.)
- Post-graduate Program in Biodiversity and Biotechnology (BIONORTE), Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil
| | - Heliton Patrick Cordovil Brígido
- Post-Graduate Program in Pharmaceutica Innovation, Institute of Health Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil; (A.R.Q.G.); (H.P.C.B.); (V.V.V.); (M.F.D.)
| | - Valdicley Vieira Vale
- Post-Graduate Program in Pharmaceutica Innovation, Institute of Health Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil; (A.R.Q.G.); (H.P.C.B.); (V.V.V.); (M.F.D.)
| | - Maria Fâni Dolabela
- Post-Graduate Program in Pharmaceutica Innovation, Institute of Health Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil; (A.R.Q.G.); (H.P.C.B.); (V.V.V.); (M.F.D.)
- Post-graduate Program in Biodiversity and Biotechnology (BIONORTE), Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil
| | - Eliete Pereira de Carvalho
- Oxidative Stress Research Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil; (N.C.); (E.L.P.V.); (E.P.d.C.)
- Post-graduate Program in Biodiversity and Biotechnology (BIONORTE), Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil
| | - Sandro Percário
- Oxidative Stress Research Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil; (N.C.); (E.L.P.V.); (E.P.d.C.)
- Post-graduate Program in Biodiversity and Biotechnology (BIONORTE), Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil
- Correspondence:
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Zhang J, Liang N, Cao Y, Li M. Differentially Expressed Circular RNAs and Their Therapeutic Mechanism in Non-segmental Vitiligo Patients Treated With Methylprednisolone. Front Med (Lausanne) 2022; 9:839066. [PMID: 35652072 PMCID: PMC9149005 DOI: 10.3389/fmed.2022.839066] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 03/30/2022] [Indexed: 01/31/2023] Open
Abstract
Vitiligo is characterized by chronic skin depigmentation arising from the autoimmune destruction of epidermal melanocytes. Systemic corticosteroid therapy is an effective immunosuppressive treatment for progressive generalized vitiligo. Circular RNAs (circRNAs) play various roles in diseases. In systemic corticosteroid therapy, however, how circRNAs function to counter vitiligo is still unclear. In this article, we identified the differentially expressed circRNAs (DEcircRNAs) in vitiligo patients before and after the administration of methylprednisolone. Total RNA was extracted from the peripheral blood of patients with vitiligo, and samples were hybridized into a circRNA array. A total of 375 (51 upregulated and 324 downregulated) circRNAs were differentially expressed. Box, scatter, volcano, and heatmap plots were generated to classify the samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on DEcircRNAs. These DEcircRNAs were enriched in vitiligo-related biological processes, such as ferroptosis, organic substance transport, protein metabolic process, and cellular component organization or biogenesis. Two different databases, TargetScan and miRanda, were used to predict circRNA/miRNA interactions. Several circRNA/miRNA interactions were involved in ferroptosis. These circRNAs might serve as therapeutic targets in the treatment of vitiligo.
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Affiliation(s)
- Jiaqi Zhang
- Department of Dermatology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, China
| | - Ning Liang
- Department of Dermatology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, China
| | - Yan Cao
- Department of Dermatology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, China
- *Correspondence: Yan Cao,
| | - Min Li
- Department of Dermatology, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Min Li,
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Jahangir S, John P, Bhatti A, Aslam MM, Mehmood Malik J, Anderson JR, Peffers MJ. LC-MS/MS-Based Serum Protein Profiling for Identification of Candidate Biomarkers in Pakistani Rheumatoid Arthritis Patients. Life (Basel) 2022; 12:life12030464. [PMID: 35330214 PMCID: PMC8955720 DOI: 10.3390/life12030464] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 03/11/2022] [Accepted: 03/15/2022] [Indexed: 11/16/2022] Open
Abstract
Rheumatoid arthritis is an autoimmune disorder of complex disease etiology. Currently available serological diagnostic markers lack in terms of sensitivity and specificity and thus additional biomarkers are warranted for early disease diagnosis and management. We aimed to screen and compare serum proteome profiles of rheumatoid arthritis serotypes with healthy controls in the Pakistani population for identification of potential disease biomarkers. Serum samples from rheumatoid arthritis patients and healthy controls were enriched for low abundance proteins using ProteoMinerTM columns. Rheumatoid arthritis patients were assigned to one of the four serotypes based on anti-citrullinated peptide antibodies and rheumatoid factor. Serum protein profiles were analyzed via liquid chromatography-tandem mass spectrometry. The changes in the protein abundances were determined using label-free quantification software ProgenesisQITM followed by pathway analysis. Findings were validated in an independent cohort of patients and healthy controls using an enzyme-linked immunosorbent assay. A total of 213 proteins were identified. Comparative analysis of all groups (false discovery rate < 0.05, >2-fold change, and identified with ≥2 unique peptides) identified ten proteins that were differentially expressed between rheumatoid arthritis serotypes and healthy controls including pregnancy zone protein, selenoprotein P, C4b-binding protein beta chain, apolipoprotein M, N-acetylmuramoyl-L-alanine amidase, catalytic chain, oncoprotein-induced transcript 3 protein, Carboxypeptidase N subunit 2, Apolipoprotein C-I and Apolipoprotein C-III. Pathway analysis predicted inhibition of liver X receptor/retinoid X receptor activation pathway and production of nitric oxide and reactive oxygen species pathway in macrophages in all serotypes. A catalogue of potential serum biomarkers for rheumatoid arthritis were identified. These biomarkers can be further evaluated in larger cohorts from different populations for their diagnostic and prognostic potential.
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Affiliation(s)
- Sidrah Jahangir
- Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan; (S.J.); (A.B.)
| | - Peter John
- Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan; (S.J.); (A.B.)
- Correspondence: ; Tel.: +92-051-9085-6151
| | - Attya Bhatti
- Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan; (S.J.); (A.B.)
| | - Muhammad Muaaz Aslam
- Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA 15216, USA;
| | | | - James R. Anderson
- Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, William Henry Duncan Building, 6 West Derby Street, Liverpool L7 8TX, UK; (J.R.A.); (M.J.P.)
| | - Mandy J. Peffers
- Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, William Henry Duncan Building, 6 West Derby Street, Liverpool L7 8TX, UK; (J.R.A.); (M.J.P.)
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Pereira JPC, Pereira FAC, Pimenta CJ. Benefits of coffee consumption for human health: an overview. CURRENT NUTRITION & FOOD SCIENCE 2022. [DOI: 10.2174/1573401318666220111151531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
Coffee is one of the most consumed beverages worldwide and is popular for its characteristic flavor and rich organoleptic properties.
Aim:
Based on published articles, the aims of this review are i) study the association between
coffee consumption and benefits to human health; ii) the effects of coffee consumption on
some pathologies; and iii) provide a description of coffee’s bioactive compounds.
Discussion:
Coffee presents bioactive compounds, which include phenolic compounds, especially chlorogenic acid (caffeoylquinic acid), trigonelline, and diterpenes, such as cafestol and
kahweol. These compounds are related to the beneficial effects for human health, including
high antioxidant activity, antimutagenic activity, hepatoprotective action, reduced incidence of
type 2 diabetes mellitus, reduced risk of cardiovascular diseases, decreased incidence of inflammatory diseases, reduced menopausal symptoms, and others. Coffee’s bioactive compounds are caffeine, chlorogenic acid, trigonelline, cafestol and kahweol, which are closely related to coffee’s beneficial effects.
Conclusion:
The present review clarified that the benefits of moderate coffee consumption
outweigh the associated risks.
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Affiliation(s)
| | | | - Carlos José Pimenta
- Department of Food Science, Federal University of Lavras, 37200-000 Lavras, MG, Brazil
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Natural Autoimmunity to Selenoprotein P Impairs Selenium Transport in Hashimoto's Thyroiditis. Int J Mol Sci 2021; 22:ijms222313088. [PMID: 34884891 PMCID: PMC8658221 DOI: 10.3390/ijms222313088] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 11/26/2021] [Accepted: 11/30/2021] [Indexed: 02/07/2023] Open
Abstract
The essential trace element selenium (Se) is needed for the biosynthesis of selenocysteine-containing selenoproteins, including the secreted enzyme glutathione peroxidase 3 (GPX3) and the Se-transporter selenoprotein P (SELENOP). Both are found in blood and thyroid colloid, where they serve protective functions. Serum SELENOP derives mainly from hepatocytes, whereas the kidney contributes most serum GPX3. Studies using transgenic mice indicated that renal GPX3 biosynthesis depends on Se supply by hepatic SELENOP, which is produced in protein variants with varying Se contents. Low Se status is an established risk factor for autoimmune thyroid disease, and thyroid autoimmunity generates novel autoantigens. We hypothesized that natural autoantibodies to SELENOP are prevalent in thyroid patients, impair Se transport, and negatively affect GPX3 biosynthesis. Using a newly established quantitative immunoassay, SELENOP autoantibodies were particularly prevalent in Hashimoto’s thyroiditis as compared with healthy control subjects (6.6% versus 0.3%). Serum samples rich in SELENOP autoantibodies displayed relatively high total Se and SELENOP concentrations in comparison with autoantibody-negative samples ([Se]; 85.3 vs. 77.1 µg/L, p = 0.0178, and [SELENOP]; 5.1 vs. 3.5 mg/L, p = 0.001), while GPX3 activity was low and correlated inversely to SELENOP autoantibody concentrations. In renal cells in culture, antibodies to SELENOP inhibited Se uptake. Our results indicate an impairment of SELENOP-dependent Se transport by natural SELENOP autoantibodies, suggesting that the characterization of health risk from Se deficiency may need to include autoimmunity to SELENOP as additional biomarker of Se status.
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Seebacher NA, Krchniakova M, Stacy AE, Skoda J, Jansson PJ. Tumour Microenvironment Stress Promotes the Development of Drug Resistance. Antioxidants (Basel) 2021; 10:1801. [PMID: 34829672 PMCID: PMC8615091 DOI: 10.3390/antiox10111801] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 10/29/2021] [Accepted: 11/08/2021] [Indexed: 01/18/2023] Open
Abstract
Multi-drug resistance (MDR) is a leading cause of cancer-related death, and it continues to be a major barrier to cancer treatment. The tumour microenvironment (TME) has proven to play an essential role in not only cancer progression and metastasis, but also the development of resistance to chemotherapy. Despite the significant advances in the efficacy of anti-cancer therapies, the development of drug resistance remains a major impediment to therapeutic success. This review highlights the interplay between various factors within the TME that collectively initiate or propagate MDR. The key TME-mediated mechanisms of MDR regulation that will be discussed herein include (1) altered metabolic processing and the reactive oxygen species (ROS)-hypoxia inducible factor (HIF) axis; (2) changes in stromal cells; (3) increased cancer cell survival via autophagy and failure of apoptosis; (4) altered drug delivery, uptake, or efflux and (5) the induction of a cancer stem cell (CSC) phenotype. The review also discusses thought-provoking ideas that may assist in overcoming the TME-induced MDR. We conclude that stressors from the TME and exposure to chemotherapeutic agents are strongly linked to the development of MDR in cancer cells. Therefore, there remains a vast area for potential research to further elicit the interplay between factors existing both within and outside the TME. Elucidating the mechanisms within this network is essential for developing new therapeutic strategies that are less prone to failure due to the development of resistance in cancer cells.
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Affiliation(s)
| | - Maria Krchniakova
- Department of Experimental Biology, Faculty of Science, Masaryk University, 62500 Brno, Czech Republic;
- International Clinical Research Center, St. Anne’s University Hospital, 65691 Brno, Czech Republic
| | - Alexandra E. Stacy
- Cancer Drug Resistance & Stem Cell Program, School of Medical Science, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia;
| | - Jan Skoda
- Department of Experimental Biology, Faculty of Science, Masaryk University, 62500 Brno, Czech Republic;
- International Clinical Research Center, St. Anne’s University Hospital, 65691 Brno, Czech Republic
| | - Patric J. Jansson
- Cancer Drug Resistance & Stem Cell Program, School of Medical Science, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia;
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, Faculty of Medicine and Health, The University of Sydney, St. Leonards, NSW 2065, Australia
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41
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Roe K. How major fungal infections can initiate severe autoimmune diseases. Microb Pathog 2021; 161:105200. [PMID: 34537272 DOI: 10.1016/j.micpath.2021.105200] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 08/12/2021] [Accepted: 09/14/2021] [Indexed: 12/22/2022]
Abstract
Several autoimmune diseases have long been linked to viral and bacterial infections. In contrast, the possibility of fungal infections causing autoimmune diseases has received almost no attention. However, major fungal infections can cause severe autoimmune diseases, by decreasing TREG cells and increasing production of interleukin-23, CD4 TH17 T-cells, interleukin-17 and other cytokines, including interleukin-22. Several factors can cause fungal infections, including antibiotic usage. Bacterial and fungal populations compete in mammalian oropharyngeal, respiratory, gastrointestinal, and genitourinary tracts. Antibiotic usage decreases bacteria and thereby favors fungal populations over bacterial populations. This leads to an explanatory hypothesis for the pathogenesis of severe autoimmune diseases by major fungal infections. The increase in fungal populations in individuals susceptible to major fungal infections can also explain the higher incidence of autoimmune diseases. CD4 TH17 T-cells and certain interleukins can be one path of pathogenesis between major fungal infections and increased incidences of major autoimmune diseases, including type 1 diabetes, multiple sclerosis, and various types of arthritis.
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Toxic Feedback Loop Involving Iron, Reactive Oxygen Species, α-Synuclein and Neuromelanin in Parkinson's Disease and Intervention with Turmeric. Mol Neurobiol 2021; 58:5920-5936. [PMID: 34426907 DOI: 10.1007/s12035-021-02516-5] [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: 03/16/2021] [Accepted: 08/03/2021] [Indexed: 12/20/2022]
Abstract
Parkinson's disease (PD) is a movement disorder associated with severe loss of mainly dopaminergic neurons in the substantia nigra. Pathological hallmarks include Lewy bodies, and loss of neuromelanin, due to degeneration of neuromelanin-containing dopaminergic neurons. Despite being described over 200 years ago, the etiology of PD remains unknown. Here, we highlight the roles of reactive oxygen species (ROS), iron, alpha synuclein (α-syn) and neuromelanin in a toxic feedback loop culminating in neuronal death and spread of the disease. Dopaminergic neurons are particularly vulnerable due to decreased antioxidant concentration with aging, constant exposure to ROS and presence of neurotoxic compounds (e.g. ortho-quinones). ROS and iron increase each other's levels, creating a state of oxidative stress. α-Syn aggregation is influenced by ROS and iron but also increases ROS and iron via its induced mitochondrial dysfunction and ferric-reductase activity. Neuromelanin's binding affinity is affected by increased ROS and iron. Furthermore, during neuronal death, neuromelanin is degraded in the extracellular space, releasing its bound toxins. This cycle of events continues to neighboring neurons in the form of a toxic loop, causing PD pathology. The increase in ROS and iron may be an important target for therapies to disrupt this toxic loop, and therefore diets rich in certain 'nutraceuticals' may be beneficial. Turmeric is an attractive candidate, as it is known to have anti-oxidant and iron chelating properties. More studies are needed to test this theory and if validated, this would be a step towards development of lifestyle-based therapeutic modalities to complement existing PD treatments.
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Liu C, Hirakawa H, Katsube T, Fang Y, Tanaka K, Nenoi M, Fujimori A, Wang B. Altered Induction of Reactive Oxygen Species by X-rays in Hematopoietic Cells of C57BL/6-Tg (CAG-EGFP) Mice. Int J Mol Sci 2021; 22:6929. [PMID: 34203224 PMCID: PMC8268547 DOI: 10.3390/ijms22136929] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 06/14/2021] [Accepted: 06/15/2021] [Indexed: 12/20/2022] Open
Abstract
Previous work pointed to a critical role of excessive production of reactive oxygen species (ROS) in increased radiation hematopoietic death in GFP mice. Meanwhile, enhanced antioxidant capability was not demonstrated in the mouse model of radio-induced adaptive response (RAR) using rescue of radiation hematopoietic death as the endpoint. ROS induction by ex vivo X-irradiation at a dose ranging from 0.1 to 7.5 Gy in the nucleated bone marrow cells was comparatively studied using GFP and wild type (WT) mice. ROS induction was also investigated in the cells collected from mice receiving a priming dose (0.5 Gy) efficient for RAR induction in WT mice. Significantly elevated background and increased induction of ROS in the cells from GFP mice were observed compared to those from WT mice. Markedly lower background and decreased induction of ROS were observed in the cells collected from WT mice but not GFP mice, both receiving the priming dose. GFP overexpression could alter background and induction of ROS by X-irradiation in hematopoietic cells. The results provide a reasonable explanation to the previous study on the fate of cells and mice after X-irradiation and confirm enhanced antioxidant capability in RAR. Investigations involving GFP overexpression should be carefully interpreted.
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Affiliation(s)
- Cuihua Liu
- Molecular and Cellular Radiation Biology Group, Department of Charged Particle Therapy Research, Institute for Quantum Medical Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan; (C.L.); (H.H.); (Y.F.)
| | - Hirokazu Hirakawa
- Molecular and Cellular Radiation Biology Group, Department of Charged Particle Therapy Research, Institute for Quantum Medical Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan; (C.L.); (H.H.); (Y.F.)
| | - Takanori Katsube
- Dietary Effects Research Group, Department of Radiation Effects Research, National Institute of Radiological Sciences, Quantum Life and Medical Science Directorate, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan; (T.K.); (K.T.)
| | - Yaqun Fang
- Molecular and Cellular Radiation Biology Group, Department of Charged Particle Therapy Research, Institute for Quantum Medical Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan; (C.L.); (H.H.); (Y.F.)
| | - Kaoru Tanaka
- Dietary Effects Research Group, Department of Radiation Effects Research, National Institute of Radiological Sciences, Quantum Life and Medical Science Directorate, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan; (T.K.); (K.T.)
| | - Mitsuru Nenoi
- Human Resources Development Center, Quantum Life and Medical Science Directorate, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan;
| | - Akira Fujimori
- Molecular and Cellular Radiation Biology Group, Department of Charged Particle Therapy Research, Institute for Quantum Medical Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan; (C.L.); (H.H.); (Y.F.)
| | - Bing Wang
- Dietary Effects Research Group, Department of Radiation Effects Research, National Institute of Radiological Sciences, Quantum Life and Medical Science Directorate, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan; (T.K.); (K.T.)
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45
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Luque-Campos N, Bustamante-Barrientos FA, Pradenas C, García C, Araya MJ, Bohaud C, Contreras-López R, Elizondo-Vega R, Djouad F, Luz-Crawford P, Vega-Letter AM. The Macrophage Response Is Driven by Mesenchymal Stem Cell-Mediated Metabolic Reprogramming. Front Immunol 2021; 12:624746. [PMID: 34149687 PMCID: PMC8213396 DOI: 10.3389/fimmu.2021.624746] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Accepted: 05/13/2021] [Indexed: 12/17/2022] Open
Abstract
Mesenchymal stem cells (MSCs) are multipotent adult stromal cells widely studied for their regenerative and immunomodulatory properties. They are capable of modulating macrophage plasticity depending on various microenvironmental signals. Current studies have shown that metabolic changes can also affect macrophage fate and function. Indeed, changes in the environment prompt phenotype change. Therefore, in this review, we will discuss how MSCs orchestrate macrophage’s metabolic plasticity and the impact on their function. An improved understanding of the crosstalk between macrophages and MSCs will improve our knowledge of MSC’s therapeutic potential in the context of inflammatory diseases, cancer, and tissue repair processes in which macrophages are pivotal.
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Affiliation(s)
- Noymar Luque-Campos
- Laboratorio de Inmunología Celular y Molecular, Facultad de Medicina, Universidad de los Andes, Santiago, Chile.,Centro de Investigación e Innovación Biomédica, Universidad de los Andes, Santiago, Chile.,Programa de Doctorado en Biomedicina, Facultad de Medicina, Universidad de los Andes, Santiago, Chile
| | - Felipe A Bustamante-Barrientos
- Laboratorio de Inmunología Celular y Molecular, Facultad de Medicina, Universidad de los Andes, Santiago, Chile.,Centro de Investigación e Innovación Biomédica, Universidad de los Andes, Santiago, Chile
| | - Carolina Pradenas
- Laboratorio de Inmunología Celular y Molecular, Facultad de Medicina, Universidad de los Andes, Santiago, Chile.,Centro de Investigación e Innovación Biomédica, Universidad de los Andes, Santiago, Chile.,Facultad de Ciencias, Universidad de Chile, Santiago, Chile
| | - Cynthia García
- Laboratorio de Inmunología Celular y Molecular, Facultad de Medicina, Universidad de los Andes, Santiago, Chile.,Centro de Investigación e Innovación Biomédica, Universidad de los Andes, Santiago, Chile.,Escuela de Biotecnología, Facultad de Ciencias, Universidad Mayor, Santiago, Chile
| | - María Jesús Araya
- Laboratorio de Inmunología Celular y Molecular, Facultad de Medicina, Universidad de los Andes, Santiago, Chile.,Centro de Investigación e Innovación Biomédica, Universidad de los Andes, Santiago, Chile.,Escuela de Biotecnología, Facultad de Ciencias, Universidad Mayor, Santiago, Chile
| | | | | | - Roberto Elizondo-Vega
- Laboratorio de Biología Celular, Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile
| | | | - Patricia Luz-Crawford
- Laboratorio de Inmunología Celular y Molecular, Facultad de Medicina, Universidad de los Andes, Santiago, Chile.,Centro de Investigación e Innovación Biomédica, Universidad de los Andes, Santiago, Chile
| | - Ana María Vega-Letter
- Centro de Investigación e Innovación Biomédica, Universidad de los Andes, Santiago, Chile.,Cells for Cells, Regenero, Las Condes, Santiago, Chile.,Laboratory of Nano-Regenerative Medicine, Facultad de Medicina, Universidad de los Andes, Santiago, Chile
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ROS Cocktails as an Adjuvant for Personalized Antitumor Vaccination? Vaccines (Basel) 2021; 9:vaccines9050527. [PMID: 34069708 PMCID: PMC8161309 DOI: 10.3390/vaccines9050527] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 05/15/2021] [Accepted: 05/17/2021] [Indexed: 12/22/2022] Open
Abstract
Cancer is the second leading cause of death worldwide. Today, the critical role of the immune system in tumor control is undisputed. Checkpoint antibody immunotherapy augments existing antitumor T cell activity with durable clinical responses in many tumor entities. Despite the presence of tumor-associated antigens and neoantigens, many patients have an insufficient repertoires of antitumor T cells. Autologous tumor vaccinations aim at alleviating this defect, but clinical success is modest. Loading tumor material into autologous dendritic cells followed by their laboratory expansion and therapeutic vaccination is promising, both conceptually and clinically. However, this process is laborious, time-consuming, costly, and hence less likely to solve the global cancer crisis. Therefore, it is proposed to re-focus on personalized anticancer vaccinations to enhance the immunogenicity of autologous therapeutic tumor vaccines. Recent work re-established the idea of using the alarming agents of the immune system, oxidative modifications, as an intrinsic adjuvant to broaden the antitumor T cell receptor repertoire in cancer patients. The key novelty is the use of gas plasma, a multi-reactive oxygen and nitrogen species-generating technology, for diversifying oxidative protein modifications in a, so far, unparalleled manner. This significant innovation has been successfully used in proof-of-concept studies and awaits broader recognition and implementation to explore its chances and limitations of providing affordable personalized anticancer vaccines in the future. Such multidisciplinary advance is timely, as the current COVID-19 crisis is inexorably reflecting the utmost importance of innovative and effective vaccinations in modern times.
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Hasegawa T, Mizugaki A, Inoue Y, Kato H, Murakami H. Cystine reduces tight junction permeability and intestinal inflammation induced by oxidative stress in Caco-2 cells. Amino Acids 2021; 53:1021-1032. [PMID: 33991253 PMCID: PMC8241805 DOI: 10.1007/s00726-021-03001-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Accepted: 05/06/2021] [Indexed: 12/16/2022]
Abstract
Intestinal oxidative stress produces pro-inflammatory cytokines, which increase tight junction (TJ) permeability, leading to intestinal and systemic inflammation. Cystine (Cys2) is a substrate of glutathione (GSH) and inhibits inflammation, however, it is unclear whether Cys2 locally improves intestinal barrier dysfunction. Thus, we investigated the local effects of Cys2 on oxidative stress-induced TJ permeability and intestinal inflammatory responses. Caco-2 cells were cultured in a Cys2-supplemented medium for 24 h and then treated with H2O2 for 2 h. We assessed TJ permeability by measuring transepithelial electrical resistance and the paracellular flux of fluorescein isothiocyanate–dextran 4 kDa. We measured the concentration of Cys2 and GSH after Cys2 pretreatment. The mRNA expression of pro-inflammatory cytokines was assessed. In addition, the levels of TJ proteins were assessed by measuring the expression of TJ proteins in the whole cells and the ratio of TJ proteins in the detergent-insoluble fractions to soluble fractions (IS/S ratio). Cys2 treatment reduced H2O2-induced TJ permeability. Cys2 did not change the expression of TJ proteins in the whole cells, however, suppressed the IS/S ratio of claudin-4. Intercellular levels of Cys2 and GSH significantly increased in cells treated with Cys2. Cys2 treatment suppressed the mRNA expression of pro-inflammatory cytokines, and the mRNA levels were significantly correlated with TJ permeability. In conclusion, Cys2 treatment locally reduced oxidative stress-induced intestinal barrier dysfunction possively due to the mitigation of claudin-4 dislocalization. Furthermore, the effect of Cys2 on the improvement of intestinal barrier function is related to the local suppression of oxidative stress-induced pro-inflammatory responses.
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Affiliation(s)
- Tatsuya Hasegawa
- Institute of Food Sciences and Technologies, Ajinomoto Co., Inc, Kanagawa, 210-8681, Japan
| | - Ami Mizugaki
- Institute of Food Sciences and Technologies, Ajinomoto Co., Inc, Kanagawa, 210-8681, Japan
| | - Yoshiko Inoue
- Institute of Food Sciences and Technologies, Ajinomoto Co., Inc, Kanagawa, 210-8681, Japan
| | - Hiroyuki Kato
- Institute of Food Sciences and Technologies, Ajinomoto Co., Inc, Kanagawa, 210-8681, Japan.
| | - Hitoshi Murakami
- Institute of Food Sciences and Technologies, Ajinomoto Co., Inc, Kanagawa, 210-8681, Japan
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Ostadkarampour M, Putnins EE. Monoamine Oxidase Inhibitors: A Review of Their Anti-Inflammatory Therapeutic Potential and Mechanisms of Action. Front Pharmacol 2021; 12:676239. [PMID: 33995107 PMCID: PMC8120032 DOI: 10.3389/fphar.2021.676239] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 04/06/2021] [Indexed: 12/18/2022] Open
Abstract
Chronic inflammatory diseases are debilitating, affect patients' quality of life, and are a significant financial burden on health care. Inflammation is regulated by pro-inflammatory cytokines and chemokines that are expressed by immune and non-immune cells, and their expression is highly controlled, both spatially and temporally. Their dysregulation is a hallmark of chronic inflammatory and autoimmune diseases. Significant evidence supports that monoamine oxidase (MAO) inhibitor drugs have anti-inflammatory effects. MAO inhibitors are principally prescribed for the management of a variety of central nervous system (CNS)-associated diseases such as depression, Alzheimer's, and Parkinson's; however, they also have anti-inflammatory effects in the CNS and a variety of non-CNS tissues. To bolster support for their development as anti-inflammatories, it is critical to elucidate their mechanism(s) of action. MAO inhibitors decrease the generation of end products such as hydrogen peroxide, aldehyde, and ammonium. They also inhibit biogenic amine degradation, and this increases cellular and pericellular catecholamines in a variety of immune and some non-immune cells. This decrease in end product metabolites and increase in catecholamines can play a significant role in the anti-inflammatory effects of MAO inhibitors. This review examines MAO inhibitor effects on inflammation in a variety of in vitro and in vivo CNS and non-CNS disease models, as well as their anti-inflammatory mechanism(s) of action.
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Affiliation(s)
- Mahyar Ostadkarampour
- Department of Oral Biological and Medical Sciences, Faculty of Dentistry, The University of British Columbia, Vancouver, BC, Canada
| | - Edward E Putnins
- Department of Oral Biological and Medical Sciences, Faculty of Dentistry, The University of British Columbia, Vancouver, BC, Canada
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Abstract
Adequate iodine intake is necessary for normal thyroid function. Iodine deficiency is associated with serious complications, but also iodine excess can lead to thyroid dysfunction, and iodine supplementation aimed to prevent iodine deficiency disorders has been associated with development of thyroid autoimmunity. The epidemiology of thyroid diseases has undergone profound changes since the implementation of iodoprophylaxis, notably by means of iodine-enriched salt, specifically resulting in decreased prevalence of goiter and neonatal hypothyroidism, improved cognitive function development in infancy, and reduced incidence of more aggressive forms of thyroid cancer. The main question we address with this review is the clinical relevance of the possible effect on autoimmunity exerted by the use of iodine-enriched salt to correct iodine deficiency. In animal models, exogenous iodine is able to trigger or exacerbate thyroid autoimmunity, but it is still not clear whether the observed immunological changes are due to a direct effect of iodine on immune response, or whether they represent a secondary response to a toxic effect of iodine on thyroid tissue. Previous iodine status of a population seems to influence the functional thyroid response to increased iodine intake and possibly the development of thyroid autoimmunity. Moreover, the prevalence of thyroid antibodies, regarded as hallmark of autoimmune thyroid disease, varies between populations under the influence of genetic and environmental factors, and the presence of thyroid antibodies does not always coincide with the presence of thyroid disease or its future development. In addition, the incidence of autoimmune diseases shows a general increasing trend in the last decades. For all these reasons, available data are quite heterogeneous and difficult to analyze and compare. In conclusion, available data from long-term population surveys show that a higher than adequate population iodine intake due to a poorly controlled program of iodine prophylaxis could induce thyroid dysfunction, including thyroid autoimmunity mostly represented by euthyroid or subclinical hypothyroid autoimmune thyroiditis. Close monitoring iodine prophylaxis is therefore advised to ensure that effects of both iodine deficiency and iodine excess are avoided.
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Tavassolifar MJ, Changaei M, Salehi Z, Ghasemi F, Javidan M, Nicknam MH, Pourmand MR. Redox imbalance in Crohn's disease patients is modulated by Azathioprine. Redox Rep 2021; 26:80-84. [PMID: 33882797 PMCID: PMC8079067 DOI: 10.1080/13510002.2021.1915665] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background Crohn's disease (CD) is a chronic inflammatory disease without a specific cause. Inflammation in these patients can disturb the oxidants/antioxidants balance and results in oxidative stress that plays a destructive role. This study aimed to evaluate the gene expression of sod1, sod2, cat, nrf2 and gp91phox in CD patients before and after Azathioprine (Aza) consumption. Method Peripheral bloodmononuclear cells (PBMCs) were separated from CD patients (n= 15, mean age = 33.6 ± 1.8) before and after treatment with Aza and healthy controls (n= 15, mean age = 31.5 ± 1.2). The expression levels of sod1, sod2, cat, nrf2 and gp91phox were measured in byusing real-time qRT-PCR technique. Result The expression levels of gp91phox (P-value < 0.001), cat (P-value < 0.05), sod1 (P-value < 0.001), nrf2 (P-value < 0.001) were significantly increased compared to control group. Following treatment with Aza, the decreased expression levels of gp91phox (P-value < 0.05), cat (P-value < 0.05), sod1(P-value < 0.001) and nrf2 (P-value < 0.001) were observed in CD patients. Conclusion Overall, our results showed that prescription of Azathioprine can lead to the altered expression of redox system-related genes in patients with CD.
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Affiliation(s)
| | - Mostafa Changaei
- Immunology Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Salehi
- Immunology Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Ghasemi
- Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Moslem Javidan
- Immunology Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mohammad Reza Pourmand
- Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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