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Pechroj S, Kaewkod T, Sattayawat P, Inta A, Suriyaprom S, Yata T, Tragoolpua Y, Promputtha I. Multifunctional Nanoemulsified Clinacanthus nutans Extract: Synergistic Anti-Pathogenic, Anti-Biofilm, Anti-Inflammatory, and Metabolic Modulation Effects against Periodontitis. BIOLOGY 2024; 13:815. [PMID: 39452124 PMCID: PMC11505571 DOI: 10.3390/biology13100815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 09/26/2024] [Accepted: 10/04/2024] [Indexed: 10/26/2024]
Abstract
This study investigates the therapeutic potential of Clinacanthus nutans extracts, focusing on the 95% ethanol (95E) extract and its nanoemulsified form, against oral pathogens and their bioactive effects. The findings demonstrate potent antibacterial activity against Streptococcus mutans and Staphylococcus aureus, essential for combating periodontal diseases, and significant anti-biofilm properties crucial for plaque management. Additionally, the extracts exhibit promising inhibitory effects on α-glucosidase enzymes, indicating potential for diabetes management through glucose metabolism regulation. Their anti-inflammatory properties, evidenced by reduced nitric oxide production, underscore their potential for treating oral infections and inflammation. Notably, the nanoemulsified 95E extract shows higher efficiency than the conventional extract, suggesting a multifunctional treatment approach for periodontal issues and metabolic disorders. These results highlight the enhanced efficacy of the nanoemulsified extract, proposing it as an effective treatment modality for periodontal disease in diabetic patients. This research offers valuable insights into the development of innovative drug delivery systems using natural remedies for improved periodontal care in diabetic populations.
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Affiliation(s)
- Sirintip Pechroj
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand; (S.P.); (T.K.); (P.S.); (A.I.); (S.S.); (Y.T.)
- Multidisciplinary and Interdisciplinary School, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Thida Kaewkod
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand; (S.P.); (T.K.); (P.S.); (A.I.); (S.S.); (Y.T.)
| | - Pachara Sattayawat
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand; (S.P.); (T.K.); (P.S.); (A.I.); (S.S.); (Y.T.)
| | - Angkhana Inta
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand; (S.P.); (T.K.); (P.S.); (A.I.); (S.S.); (Y.T.)
| | - Sureeporn Suriyaprom
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand; (S.P.); (T.K.); (P.S.); (A.I.); (S.S.); (Y.T.)
- Office of Research Administration, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Teerapong Yata
- Premier Innova Co., Ltd., Nong Bon, Prawet, Bangkok 10250, Thailand;
| | - Yingmanee Tragoolpua
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand; (S.P.); (T.K.); (P.S.); (A.I.); (S.S.); (Y.T.)
| | - Itthayakorn Promputtha
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand; (S.P.); (T.K.); (P.S.); (A.I.); (S.S.); (Y.T.)
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Lai Q, Wang X, Lai Z, Lai Y, Ye L, Liu S, Yang B, Man M. Stratum corneum hydration levels are negatively correlated with HbA1c levels in the elderly Chinese. J Diabetes 2024; 16:e70022. [PMID: 39463020 PMCID: PMC11513436 DOI: 10.1111/1753-0407.70022] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 08/05/2024] [Accepted: 10/14/2024] [Indexed: 10/29/2024] Open
Abstract
Highlights Stratum corneum hydration levels are negatively correlated with HbA1c levels and positively correlated with skin surface pH. Individuals with type 2 diabetes display lower levels of stratum corneum hydration. Because low stratum corneum hydration levels can increase circulating levels of proinflammatory cytokines, which are linked to the pathogenesis of type 2 diabetes, improvement in stratum corneum hydration can be an alternative approach in the management of type 2 diabetes.
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Affiliation(s)
- Qingsong Lai
- Department of DermatologyMedical Center for Public Health of PuningPuning CityChina
| | - Xiaohua Wang
- Dermatology HospitalSouthern Medical UniversityGuangzhouChina
| | - Zebin Lai
- Department of DermatologyMedical Center for Public Health of PuningPuning CityChina
| | - Yulin Lai
- Department of DermatologyMaternal and Child Health Care Hospital of PunningPuning CityChina
| | - Li Ye
- Dermatology HospitalSouthern Medical UniversityGuangzhouChina
| | - Sha Liu
- Department of DermatologyMedical Center for Public Health of PuningPuning CityChina
| | - Bin Yang
- Dermatology HospitalSouthern Medical UniversityGuangzhouChina
| | - Mao‐Qiang Man
- Dermatology HospitalSouthern Medical UniversityGuangzhouChina
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Lei D, Zhang J, Zhu T, Zhang L, Man MQ. Interplay between diabetes mellitus and atopic dermatitis. Exp Dermatol 2024; 33:e15116. [PMID: 38886904 DOI: 10.1111/exd.15116] [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: 01/28/2024] [Revised: 05/07/2024] [Accepted: 05/24/2024] [Indexed: 06/20/2024]
Abstract
Inflammatory dermatoses such as atopic dermatitis (AD) have long been linked to the pathogenesis of diabetes mellitus. Indeed, numerous studies show an increased risk of diabetes mellitus in individuals with AD although lower prevalence of diabetes mellitus is also observed in few studies. Though the underlying mechanisms accounting for the reciprocal influence between these two conditions are still unclear, the complex interplay between diabetes mellitus and AD is attributable, in part, to genetic and environmental factors, cytokines, epidermal dysfunction, as well as drugs used for the treatment of AD. Proper management of one condition can mitigate the other condition. In this review, we summarize the evidence of the interaction between diabetes mellitus and AD, and discuss the possible underlying mechanisms by which these two conditions influence each other.
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Affiliation(s)
- Dongyun Lei
- Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China
| | - Jiechen Zhang
- Department of Dermatology, Tongren Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China
| | - Tingting Zhu
- Department of Dermatology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Litao Zhang
- Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China
| | - Mao-Qiang Man
- Dermatology Hospital, Southern Medical University, Guangzhou, China
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Reis M, Teixeira A, Cardoso J, Borges T, Caldas Afonso A, Correia-Costa L. Association between proinflammatory cytokines and arterial stiffness in type 1 diabetic adolescents. J Pediatr Endocrinol Metab 2024; 37:405-412. [PMID: 38592062 DOI: 10.1515/jpem-2023-0530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 03/03/2024] [Indexed: 04/10/2024]
Abstract
OBJECTIVES Type 1 diabetes mellitus is considered a state of chronic low-grade inflammation and activation of the innate immune system, which is regulated by several proinflammatory cytokines and other acute-phase reactants. Arterial stiffness, a dynamic property of the vessels evaluated by the determination of pulse wave velocity (PWV), is increased in diabetic patients and is associated with microvascular and macrovascular complications of diabetes and higher cardiovascular risk. In the present study, we aimed to compare the proinflammatory state and arterial stiffness in diabetic and non-diabetic adolescents, and to characterize the association between these two parameters. METHODS Twenty-three type 1 diabetic patients, aged 12-16 years, followed at a tertiary center, and 23 adolescents nonoverweighted healthy controls, from a Portuguese birth-cohort, were included in the present analysis. Anthropometry, blood pressure, glycemic control data, and lipid parameters were collected. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity. Proinflammatory cytokines' concentrations (TNF-α, IL-1β, IL-6, IL-10, IFN-γ, and GM-CSF) were quantified by multiplex immunoassays using a Luminex 200 analyzer. RESULTS There were no statistically significant differences between the proinflammatory cytokines' concentrations in the two groups. PWV [6.63 (6.23-7.07) vs. 6.07 (5.15-6.65) m/s, p=0.015] was significantly higher in the diabetic group. PWV was negatively correlated with GM-CSF (ρ=-0.437, p=0.037) in the diabetic group. A linear association was found between diabetes duration and PWV (with PWV increasing by 0.094 m/s (95 % confidence interval, 0.019 to 0.169) per month of disease duration). In the diabetic group, HbA1c was negatively correlated with IL-10 (ρ=-0.473, p=0.026). Negative correlations were also found between IL-10 and total, HDL, and LDL cholesterol only in the diabetic group. CONCLUSIONS Diabetic adolescent patients present higher PWV, when compared to their healthy counterparts, even though we could not find differences in the levels of several proinflammatory cytokines between the two groups. The negative correlation found between IL-10 and HbA1c might translate a protective counterbalance effect of this anti-inflammatory cytokine, which might also explain the negative correlations found with blood lipids. Further studies are needed to better clarify the association between arterial stiffness and the proinflammatory milieu of diabetes.
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Affiliation(s)
- Mónica Reis
- Instituto de Ciências Biomédicas Abel Salazar, 89239 Universidade do Porto , Porto, Portugal
- 522166 Centro Hospitalar Universitário de Santo António , Porto, Portugal
| | - Ana Teixeira
- EPIUnit - Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal
- Division of Pediatric Nephrology, Centro Materno-Infantil do Norte, 522166 Centro Hospitalar Universitário do Porto , Porto, Portugal
| | - Juliana Cardoso
- Division of Pediatrics, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário de Santo António, Porto, Portugal
| | - Teresa Borges
- Instituto de Ciências Biomédicas Abel Salazar, 89239 Universidade do Porto , Porto, Portugal
- Division of Pediatric Endocrinology, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário de Santo António, Porto, Portugal
| | - Alberto Caldas Afonso
- Instituto de Ciências Biomédicas Abel Salazar, 89239 Universidade do Porto , Porto, Portugal
- EPIUnit - Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal
- Division of Pediatric Nephrology, Centro Materno-Infantil do Norte, 522166 Centro Hospitalar Universitário do Porto , Porto, Portugal
- Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR), Universidade do Porto, Porto, Portugal
- CAC ICBAS-CHP - Centro Académico Clínico Instituto de Ciências Biomédicas Abel Salazar - Centro Hospitalar Universitário de Santo António, Porto, Portugal
| | - Liane Correia-Costa
- Instituto de Ciências Biomédicas Abel Salazar, 89239 Universidade do Porto , Porto, Portugal
- EPIUnit - Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal
- Division of Pediatric Nephrology, Centro Materno-Infantil do Norte, 522166 Centro Hospitalar Universitário do Porto , Porto, Portugal
- Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR), Universidade do Porto, Porto, Portugal
- CAC ICBAS-CHP - Centro Académico Clínico Instituto de Ciências Biomédicas Abel Salazar - Centro Hospitalar Universitário de Santo António, Porto, Portugal
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Taneera J, Khalique A, Mohammed AK, Mussa BM, Sulaiman N, Abu-Gharbieh E, El-Huneidi W, Saber-Ayad MM. Investigating the Impact of IL6 on Insulin Secretion: Evidence from INS-1 Cells, Human Pancreatic Islets, and Serum Analysis. Cells 2024; 13:685. [PMID: 38667300 PMCID: PMC11049194 DOI: 10.3390/cells13080685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 04/11/2024] [Accepted: 04/12/2024] [Indexed: 04/28/2024] Open
Abstract
Interleukin-6 (IL6) is a pleiotropic cytokine implicated in metabolic disorders and inflammation, yet its precise influence on insulin secretion and glucose metabolism remains uncertain. This study examined IL6 expression in pancreatic islets from individuals with/without diabetes, alongside a series of functional experiments, including siRNA silencing; IL6 treatment; and assessments of glucose uptake, cell viability, apoptosis, and expression of key β-cell genes, which were conducted in both INS-1 cells and human islets to elucidate the effect of IL6 on insulin secretion. Serum levels of IL6 from Emirati patients with type 2 diabetes (T2D) were measured, and the effect of antidiabetic drugs on IL6 levels was studied. The results revealed that IL6 mRNA expression was higher in islets from diabetic and older donors compared to healthy or young donors. IL6 expression correlated negatively with PDX1, MAFB, and NEUROD1 and positively with SOX4, HES1, and FOXA1. Silencing IL6 in INS-1 cells reduced insulin secretion and glucose uptake independently of apoptosis or oxidative stress. Reduced expression of IL6 was associated with the downregulation of Ins, Pdx1, Neurod1, and Glut2 in INS-1 cells. In contrast, IL6 treatment enhanced insulin secretion in INS-1 cells and human islets and upregulated insulin expression. Serum IL6 levels were elevated in patients with T2D and associated with higher glucose, HbA1c, and triglycerides, regardless of glucose-lowering medications. This study provides a new understanding of the role of IL6 in β-cell function and the pathophysiology of T2D. Our data highlight differences in the response to IL6 between INS-1 cells and human islets, suggesting the presence of species-specific variations across different experimental models. Further research is warranted to unravel the precise mechanisms underlying the observed effects of IL-6 on insulin secretion.
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Affiliation(s)
- Jalal Taneera
- College of Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates; (B.M.M.); (N.S.); (E.A.-G.); (W.E.-H.); (M.M.S.-A.)
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates; (A.K.); (A.K.M.)
| | - Anila Khalique
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates; (A.K.); (A.K.M.)
| | - Abdul Khader Mohammed
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates; (A.K.); (A.K.M.)
| | - Bashair M. Mussa
- College of Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates; (B.M.M.); (N.S.); (E.A.-G.); (W.E.-H.); (M.M.S.-A.)
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates; (A.K.); (A.K.M.)
| | - Nabil Sulaiman
- College of Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates; (B.M.M.); (N.S.); (E.A.-G.); (W.E.-H.); (M.M.S.-A.)
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates; (A.K.); (A.K.M.)
| | - Eman Abu-Gharbieh
- College of Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates; (B.M.M.); (N.S.); (E.A.-G.); (W.E.-H.); (M.M.S.-A.)
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates; (A.K.); (A.K.M.)
- School of Pharmacy, The University of Jordan, Amman 11942, Jordan
| | - Waseem El-Huneidi
- College of Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates; (B.M.M.); (N.S.); (E.A.-G.); (W.E.-H.); (M.M.S.-A.)
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates; (A.K.); (A.K.M.)
| | - Maha M. Saber-Ayad
- College of Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates; (B.M.M.); (N.S.); (E.A.-G.); (W.E.-H.); (M.M.S.-A.)
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates; (A.K.); (A.K.M.)
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Yuan S, He W, Liu B, Liu Z. Research Progress on the Weak Immune Response to the COVID-19 Vaccine in Patients with Type 2 Diabetes. Viral Immunol 2024; 37:79-88. [PMID: 38498797 DOI: 10.1089/vim.2023.0097] [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: 03/20/2024] Open
Abstract
Coronavirus Disease 2019 (COVID-19) is generally susceptible to the population, highly infectious, rapidly transmitted, and highly fatal. There is a lack of specific drugs against the virus at present and vaccination is the most effective strategy to prevent infection. However, studies have found that some groups, particularly patients with diabetes, show varying degrees of weak immune reactivity to various COVID-19 vaccines, resulting in poor preventive efficacy against the novel coronavirus in patients with diabetes. Therefore, in this study, patients with type 2 diabetes mellitus (T2DM) who had weak immune response to the COVID-19 vaccine in recent years were analyzed. This article reviews the phenomenon, preliminary mechanism, and related factors affecting weak vaccine response in patients with T2DM, which is expected to help in the development of new vaccines for high-risk groups for COVID-19.
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Affiliation(s)
- Shiqi Yuan
- Department of Laboratory Medicine, Hengyang Medical School, The Second Affiliated Hospital, University of South China, Hengyang, China
| | - Wenwen He
- Department of Laboratory Medicine, Hengyang Medical School, The Second Affiliated Hospital, University of South China, Hengyang, China
| | - Bin Liu
- Department of Laboratory Medicine, Hengyang Medical School, The Second Affiliated Hospital, University of South China, Hengyang, China
| | - Zhuoran Liu
- Department of Laboratory Medicine, Hengyang Medical School, The Second Affiliated Hospital, University of South China, Hengyang, China
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Peng W, Zhang M, Yi X. Systemic Inflammatory Mediator Levels in Non-Proliferative Diabetic Retinopathy Patients with Diabetic Macular Edema. Curr Eye Res 2024; 49:80-87. [PMID: 37804222 DOI: 10.1080/02713683.2023.2268306] [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: 02/07/2023] [Accepted: 10/04/2023] [Indexed: 10/09/2023]
Abstract
PURPOSE To study the systemic inflammatory mediator levels in non-proliferative diabetic retinopathy (NPDR) patients with diabetic macular edema (DME) and explore the correlation between systemic inflammatory mediators and DME. METHODS In this prospective study, we included 25 patients without diabetes (control group) and 75 patients with type 2 diabetes mellitus (diabetic group). According to fundus examination, the diabetic group patients were divided into: diabetic patients without diabetic retinopathy (DR) (Non-DR group), NPDR patients without DME (Non-DME group), and NPDR patients with DME (DME group). Serum levels of a broad panel of inflammatory mediators were analysed by multiplex protein quantitative detection technology based on a flow cytometry detection system. RESULTS The interferon-γ (IFN-γ) levels were significantly higher in DME group and Non-DME group as compared to control group (p = 0.023 and p = 0.033) and Non-DR group (p = 0.009 and p = 0.015). Significantly higher values were obtained in DME group and Non-DME group as compared to control group for the interleukin-8 (IL-8) (p = 0.003 and p = 0.003). The IL-23 levels were significantly elevated in DME group and Non-DR group than in Non-DME group (p = 0.013 and p = 0.004). The diabetic group had significantly higher serum levels of IL-8 and IL-33 (p = 0.001 and p = 0.011), and lower serum levels of tumor necrosis factor-α (TNF-α) (p = 0.027) in comparison with control group. CONCLUSIONS The changed levels of serum inflammatory mediators suggest that the systemic inflammatory mediators are involved in the pathogenesis of NPDR patients with DME. Such effects can guide clinical monitoring, diagnostic and therapeutic approaches for DME patients at an early stage.
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Affiliation(s)
- Wenyi Peng
- Department of Ophthalmology, The First Affiliated Hospital of Xinjiang Medical University, Urumchi, China
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumchi, China
| | - Mingmei Zhang
- Department of Ophthalmology, The First Affiliated Hospital of Xinjiang Medical University, Urumchi, China
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumchi, China
| | - Xianglong Yi
- Department of Ophthalmology, The First Affiliated Hospital of Xinjiang Medical University, Urumchi, China
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Vivek S, Crimmins EM, Prizment AE, Meier HCS, Ramasubramanian R, Barcelo H, Faul J, Thyagarajan B. Age-related Differences in T-cell Subsets and Markers of Subclinical Inflammation in Aging Are Independently Associated With Type 2 Diabetes in the Health and Retirement Study. Can J Diabetes 2023; 47:594-602.e6. [PMID: 37269981 PMCID: PMC10592537 DOI: 10.1016/j.jcjd.2023.05.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 05/02/2023] [Accepted: 05/26/2023] [Indexed: 06/05/2023]
Abstract
OBJECTIVES Age-related changes in adaptive immunity and subclinical inflammation are both important risk factors for diabetes in older adults. We evaluated the independent association between T-cell subsets, subclinical inflammation, and diabetes risk in the Health and Retirement Study (HRS). METHODS We measured 11 T-cell subsets, 5 pro-inflammatory markers, and 2 anti-inflammatory markers from the 2016 wave of the HRS (baseline). Diabetes/prediabetes status was estimated at the 2016, 2018, and 2020 waves of HRS, based on levels of blood glucose/glycated hemoglobin in plasma or self-reported status. We used survey generalized logit models to evaluate the cross-sectional associations and Cox proportional hazard models to evaluate longitudinal associations. RESULTS Among 8,540 participants (56 to 107 years of age), 27.6% had prevalent type 2 diabetes and 31.1% had prediabetes in the 2016 survey. After adjusting for age, sex, race/ethnicity, education, obesity, smoking, comorbidity index, and cytomegalovirus seropositivity, individuals with type 2 diabetes had lower naive T cells and higher memory and terminal effector T cells as compared with normoglycemic individuals. Among 3,230 normoglycemic participants in the 2016 survey, the incidence of diabetes was 1.8% over 4 years of follow-up. The baseline percentage of CD4+ effector memory T cells was associated with a lower risk of incident diabetes (hazard ratio [HR]=0.63, 95% confidence interval [CI] 0.49 to 0.80, p=0.0003) after adjustment for covariates. Baseline level of interleukin-6 (IL-6) was associated with risk of incident diabetes (HR=1.52, 95% CI 1.18 to 1.97, p=0.002). The associations between age-related changes in CD4+ effector memory T cells and risk of incident diabetes remained unchanged after adjustment for subclinical inflammation, although adjusting for CD4+ effector memory T cells nullified the association between IL-6 and incident diabetes. CONCLUSIONS This study showed that the baseline percentage of CD4+ effector memory T cells was inversely associated with incident diabetes independent of subclinical inflammation, but CD4+ effector memory T-cell subsets affected the relationship between IL-6 and incident diabetes. Further studies are needed to confirm and investigate mechanisms by which T-cell immunity affects diabetes risk.
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Affiliation(s)
- Sithara Vivek
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, United States
| | - Eileen M Crimmins
- Davis School of Gerontology, University of Southern California, Los Angeles, California, United States
| | - Anna E Prizment
- Division of Hematology, Oncology and Transplantation, Medical School, University of Minnesota, Minneapolis, Minnesota, United States
| | - Helen C S Meier
- Institute for Social Research, Survey Research Center, University of Michigan, Ann Arbor, Michigan, United States
| | - Ramya Ramasubramanian
- Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, Minnesota, United States
| | - Helene Barcelo
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, United States
| | - Jessica Faul
- Institute for Social Research, Survey Research Center, University of Michigan, Ann Arbor, Michigan, United States
| | - Bharat Thyagarajan
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, United States.
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Sater MS, AlDehaini DMB, Malalla ZHA, Ali ME, Giha HA. Plasma IL-6, TREM1, uPAR, and IL6/IL8 biomarkers increment further witnessing the chronic inflammation in type 2 diabetes. Horm Mol Biol Clin Investig 2023; 44:259-269. [PMID: 36848486 DOI: 10.1515/hmbci-2022-0103] [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: 11/15/2022] [Accepted: 02/12/2023] [Indexed: 03/01/2023]
Abstract
OBJECTIVES Type 2 diabetes (T2D) is known to be associated with chronic inflammation, but the inflammatory regulators/markers are not exactly defined and the link between them remains undetermined. The objective of this study is to identify these markers by testing traditional (IL6 & IL8) and non-traditional (TREM1 & uPAR) inflammatory markers. METHODS Data and blood samples were obtained from 114 T2D and 74 non-diabetic Kuwaiti subjects attending health facilities in Kuwait. Chemical analyzers were used to measure glycemic and lipid profiles, while ELISA was used to measure plasma levels of insulin and several inflammatory markers. RESULTS Showed that the IL-6 and TREM1 were significantly higher in T2D compared to non-diabetic controls, and the uPAR level was borderline higher in T2D but significantly correlated with IL-6 levels. Unexpectedly, IL8 was significantly below normal in T2D and IL6/IL8 ratio was significantly higher in T2D patients. Unlike other tested markers, uPAR was in addition strongly correlated with insulin levels and HOMA-IR index. CONCLUSIONS Raised levels of IL6, TREMI, IL6/IL8 ratio, and the strong positive correlation of plasma levels of uPAR with IL-6, insulin, and HOMA-IR index, are reliable spectators of chronic inflammation in T2D patients. The reduced level of IL-8 in T2D was a peculiar observation that needs further explanation. Finally, the consequences and impact of the sustained rise of these inflammatory regulators in diabetic tissues need to be meticulously explored.
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Affiliation(s)
- Mai S Sater
- Department of Medical Biochemistry, College of Medicine and Medical Sciences (CMMS), Arabian Gulf University (AGU), Manama, Kingdom of Bahrain
| | | | - Zainab Hasan Abdulla Malalla
- Department of Medical Biochemistry, College of Medicine and Medical Sciences (CMMS), Arabian Gulf University (AGU), Manama, Kingdom of Bahrain
| | - Muhalab E Ali
- Department of Medical Biochemistry, College of Medicine and Medical Sciences (CMMS), Arabian Gulf University (AGU), Manama, Kingdom of Bahrain
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Niu H, Guan Y, Zhong T, Ma L, Zayed M, Guan J. Thermosensitive and antioxidant wound dressings capable of adaptively regulating TGFβ pathways promote diabetic wound healing. NPJ Regen Med 2023; 8:32. [PMID: 37422462 PMCID: PMC10329719 DOI: 10.1038/s41536-023-00313-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 06/27/2023] [Indexed: 07/10/2023] Open
Abstract
Various therapies have been utilized for treating diabetic wounds, yet current regiments do not simultaneously address the key intrinsic causes of slow wound healing, i.e., abnormal skin cell functions (particularly migration), delayed angiogenesis, and chronic inflammation. To address this clinical gap, we develop a wound dressing that contains a peptide-based TGFβ receptor II inhibitor (PTβR2I), and a thermosensitive and reactive oxygen species (ROS)-scavenging hydrogel. The wound dressing can quickly solidify on the diabetic wounds following administration. The released PTβR2I inhibits the TGFβ1/p38 pathway, leading to improved cell migration and angiogenesis, and decreased inflammation. Meanwhile, the PTβR2I does not interfere with the TGFβ1/Smad2/3 pathway that is required to regulate myofibroblasts, a critical cell type for wound healing. The hydrogel's ability to scavenge ROS in diabetic wounds further decreases inflammation. Single-dose application of the wound dressing significantly accelerates wound healing with complete wound closure after 14 days. Overall, using wound dressings capable of adaptively modulating TGFβ pathways provides a new strategy for diabetic wound treatment.
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Affiliation(s)
- Hong Niu
- Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO, USA
| | - Ya Guan
- Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO, USA
- Institute of Materials Science and Engineering, Washington University in St. Louis, St. Louis, MO, USA
| | - Ting Zhong
- Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO, USA
| | - Liang Ma
- Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Mohamed Zayed
- Department of Surgery, Section of Vascular Surgery, Washington University School of Medicine, St. Louis, MO, USA
- Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA
- Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA
| | - Jianjun Guan
- Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO, USA.
- Institute of Materials Science and Engineering, Washington University in St. Louis, St. Louis, MO, USA.
- Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA.
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11
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Thimmappa PY, Vasishta S, Ganesh K, Nair AS, Joshi MB. Neutrophil (dys)function due to altered immuno-metabolic axis in type 2 diabetes: implications in combating infections. Hum Cell 2023:10.1007/s13577-023-00905-7. [PMID: 37115481 DOI: 10.1007/s13577-023-00905-7] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 03/31/2023] [Indexed: 04/29/2023]
Abstract
Metabolic and inflammatory pathways are highly interdependent, and both systems are dysregulated in Type 2 diabetes (T2D). T2D is associated with pre-activated inflammatory signaling networks, aberrant cytokine production and increased acute phase reactants which leads to a pro-inflammatory 'feed forward loop'. Nutrient 'excess' conditions in T2D with hyperglycemia, elevated lipids and branched-chain amino acids significantly alter the functions of immune cells including neutrophils. Neutrophils are metabolically active cells and utilizes energy from glycolysis, stored glycogen and β-oxidation while depending on the pentose phosphate pathway for NADPH for performing effector functions such as chemotaxis, phagocytosis and forming extracellular traps. Metabolic changes in T2D result in constitutive activation and impeded acquisition of effector or regulatory activities of neutrophils and render T2D subjects for recurrent infections. Increased flux through the polyol and hexosamine pathways, elevated production of advanced glycation end products (AGEs), and activation of protein kinase C isoforms lead to (a) an enhancement in superoxide generation; (b) the stimulation of inflammatory pathways and subsequently to (c) abnormal host responses. Neutrophil dysfunction diminishes the effectiveness of wound healing, successful tissue regeneration and immune surveillance against offending pathogens. Hence, Metabolic reprogramming in neutrophils determines frequency, severity and duration of infections in T2D. The present review discusses the influence of the altered immuno-metabolic axis on neutrophil dysfunction along with challenges and therapeutic opportunities for clinical management of T2D-associated infections.
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Affiliation(s)
- Pooja Yedehalli Thimmappa
- Department of Ageing Research, Manipal School of Life Sciences, Manipal Academy of Higher Education, Planetarium Complex, Manipal, Karnataka, 576104, India
| | - Sampara Vasishta
- Department of Ageing Research, Manipal School of Life Sciences, Manipal Academy of Higher Education, Planetarium Complex, Manipal, Karnataka, 576104, India
| | - Kailash Ganesh
- Department of Ageing Research, Manipal School of Life Sciences, Manipal Academy of Higher Education, Planetarium Complex, Manipal, Karnataka, 576104, India
| | - Aswathy S Nair
- Department of Ageing Research, Manipal School of Life Sciences, Manipal Academy of Higher Education, Planetarium Complex, Manipal, Karnataka, 576104, India
| | - Manjunath B Joshi
- Department of Ageing Research, Manipal School of Life Sciences, Manipal Academy of Higher Education, Planetarium Complex, Manipal, Karnataka, 576104, India.
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12
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Affiliation(s)
- Rebecca A. Keogh
- Department of Immunology and Microbiology, University of Colorado Anschutz, Aurora, Colorado, United States of America
| | - Kelly S. Doran
- Department of Immunology and Microbiology, University of Colorado Anschutz, Aurora, Colorado, United States of America
- * E-mail:
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13
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Nassar M, Misra A, Bloomgarden Z. COVID-19 Vaccination in Persons with Diabetes: How they Work. CONTEMPORARY ENDOCRINOLOGY 2023:195-206. [DOI: 10.1007/978-3-031-28536-3_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/24/2023]
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14
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Keogh RA, Haeberle AL, Langouët-Astrié CJ, Kavanaugh JS, Schmidt EP, Moore GD, Horswill AR, Doran KS. Group B Streptococcus adaptation promotes survival in a hyperinflammatory diabetic wound environment. SCIENCE ADVANCES 2022; 8:eadd3221. [PMID: 36367946 PMCID: PMC9651866 DOI: 10.1126/sciadv.add3221] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 09/22/2022] [Indexed: 06/16/2023]
Abstract
Diabetic wounds have poor healing outcomes due to the presence of numerous pathogens and a dysregulated immune response. Group B Streptococcus (GBS) is commonly isolated from diabetic wound infections, but the mechanisms of GBS virulence during these infections have not been investigated. Here, we develop a murine model of GBS diabetic wound infection and, using dual RNA sequencing, demonstrate that GBS infection triggers an inflammatory response. GBS adapts to this hyperinflammatory environment by up-regulating virulence factors including those known to be regulated by the two-component system covRS, such as the surface protein pbsP, and the cyl operon, which is responsible for hemolysin/pigmentation production. We recover hyperpigmented/hemolytic GBS colonies from the murine diabetic wound, which we determined encode mutations in covR. We further demonstrate that GBS mutants in cylE and pbsP are attenuated in the diabetic wound. This foundational study provides insight into the pathogenesis of GBS diabetic wound infections.
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Affiliation(s)
- Rebecca A. Keogh
- Department of Immunology and Microbiology, University of Colorado Anschutz, Aurora, CO, USA
| | - Amanda L. Haeberle
- Department of Immunology and Microbiology, University of Colorado Anschutz, Aurora, CO, USA
| | | | - Jeffrey S. Kavanaugh
- Department of Immunology and Microbiology, University of Colorado Anschutz, Aurora, CO, USA
| | - Eric P. Schmidt
- Department of Medicine–Pulmonary Sciences and Critical Care, University of Colorado Anschutz, Aurora, CO, USA
| | - Garrett D. Moore
- Department of Orthopedics, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Alexander R. Horswill
- Department of Immunology and Microbiology, University of Colorado Anschutz, Aurora, CO, USA
- Department of Veterans Affairs Eastern Colorado Healthcare System, Aurora, CO, USA
| | - Kelly S. Doran
- Department of Immunology and Microbiology, University of Colorado Anschutz, Aurora, CO, USA
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15
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Boroumand AB, Forouhi M, Karimi F, Moghadam AS, Naeini LG, Kokabian P, Naderi D. Immunogenicity of COVID-19 vaccines in patients with diabetes mellitus: A systematic review. Front Immunol 2022; 13:940357. [PMID: 36105809 PMCID: PMC9465310 DOI: 10.3389/fimmu.2022.940357] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 07/12/2022] [Indexed: 12/16/2022] Open
Abstract
PURPOSE To evaluate the immunogenicity of COVID-19 vaccines in patients with diabetes mellitus (DM) through a systematic approach. METHOD A comprehensive search was conducted in PubMed, Scopus, and Web of Science with no time restrictions. The search was based on the three main concepts: Covid-19, Vaccine immunogenicity and Diabetes Mellitus. RESULTS After excluding irrelevant studies, 16 studies remained for the quantitative assay. Among the sixteen studies, eleven had controls. Type of diabetes was specifically mentioned in six studies (T2DM; n=4, T1DM and T2DM; n=2). Twelve of the included studies were conducted on the immunogenicity of vaccines that included mRNA vaccines (i.e. BNT162b2 and mRNA-1273) in DM, five studies included vector-based vaccines (i.e. Ad5-nCoV and ChAdOx1-S), and five studies assessed the immunogenicity of vaccines in DM, including inactivated vaccines (i.e. BBV-152, CoronaVac, Sinopharm or SinoVac). Most of the current studies indicate lower antibody response in patients with DM compared to individuals without DM, after the second dose of vaccine and irrespective of vaccine type. Several studies have shown that higher age and higher BMI are associated with lower antibody response, while optimum glycemic control and higher GFR are associated with higher antibody response among patients with DM. CONCLUSION Immunogenicity of the vaccines has mostly been reported to be lower among patients with DM compared to healthy controls. There are also few studies assessing variables that significantly affect this association, including age, type of diabetes, BMI, glycemic control and eGFR. Investigating these associations could help us provide the most advantageous condition for patients with DM before, during and after vaccination for optimum antibody response. Many unresolved issues concerning potential factors affecting vaccine immunogenicity, including type of vaccine, numbers of administered doses, re-vaccination intervals and hyperglycemia in patients with DM need to be addressed through future research.
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Affiliation(s)
- Amir Bahador Boroumand
- Department of Emergency Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mahtab Forouhi
- Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | | | | | - Pajman Kokabian
- Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Delaram Naderi
- Student Research Committee, Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
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16
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Jatoi HN, Abbas S, Abbasi MS, Tauni MA, Ghazanfar S, Zafar Malick MD, Umar MF, Tahir MJ, Asghar MS, Ahmed A. BNT162b2 vaccine considerations for immunocompromised individuals: A global perspective. Ann Med Surg (Lond) 2022; 78:103796. [PMID: 35603097 PMCID: PMC9110302 DOI: 10.1016/j.amsu.2022.103796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Revised: 05/10/2022] [Accepted: 05/11/2022] [Indexed: 12/01/2022] Open
Abstract
With the emergence of COVID-19 vaccines, individuals with comorbidities and immunosuppression require particular attention and should be prioritized for vaccination. However, the majority of vaccine clinical trials excluded people with comorbidities, resulting in a lack of data regarding vaccine efficacy in this demographic. Along with more inclusivity in clinical trials, reaching a definitive conclusion regarding vaccine efficacy in these patients is also crucial. In our review, we highlight the BNT162b2 vaccine safety and efficacy based on the limited number of clinical trials which included this demographic. We also provide vaccine considerations for individuals with cancer, autoimmune diseases, HIV, obesity, diabetes, organ transplant recipients and those undergoing maintenance haemodialysis to help them govern their decision regarding vaccine administration. In conclusion, further studies are required to alleviate any insecurities in patients with comorbidities regarding vaccination and it is recommended that patients are monitored post-vaccination to make sure sufficient immunity is achieved.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Ali Ahmed
- School of Pharmacy, Monash University, Jalan Lagoon Selatan, Bandar Sunway, 47500, Subang Jaya, Selangor, Malaysia
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17
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Hyperglycemia Induces Inflammatory Response of Human Macrophages to CD163-Mediated Scavenging of Hemoglobin-Haptoglobin Complexes. Int J Mol Sci 2022; 23:ijms23031385. [PMID: 35163309 PMCID: PMC8836198 DOI: 10.3390/ijms23031385] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 01/17/2022] [Accepted: 01/19/2022] [Indexed: 01/27/2023] Open
Abstract
Hyperglycemia, a hallmark of diabetes, can induce inflammatory programming of macrophages. The macrophage scavenger receptor CD163 internalizes and degrades hemoglobin-haptoglobin (Hb-Hp) complexes built due to intravascular hemolysis. Clinical studies have demonstrated a correlation between impaired scavenging of Hb-Hp complexes via CD163 and diabetic vascular complications. Our aim was to identify whether hyperglycemia is able to amplify inflammation via Hb-Hp complex interactions with the immune system. M(IFNγ), M(IL-4), and control M0 macrophages were differentiated out of primary human monocytes in normo- (5 mM) and hyperglycemic (25 mM) conditions. CD163 gene expression was decreased 5.53 times in M(IFNγ) with a further decrease of 1.99 times in hyperglycemia. Hyperglycemia suppressed CD163 surface expression in M(IFNγ) (1.43 times). Flow cytometry demonstrated no impairment of Hb-Hp uptake in hyperglycemia. However, hyperglycemia induced an inflammatory response of M(IFNγ) to Hb-Hp1-1 and Hb-Hp2-2 uptake with different dynamics. Hb-Hp1-1 uptake stimulated IL-6 release (3.03 times) after 6 h but suppressed secretion (5.78 times) after 24 h. Contrarily, Hb-Hp2-2 uptake did not affect IL-6 release after 6h but increased secretion after 24 h (3.06 times). Our data show that hyperglycemia induces an inflammatory response of innate immune cells to Hb-Hp1-1 and Hb-Hp2-2 uptake, converting the silent Hb-Hp complex clearance that prevents vascular damage into an inflammatory process, hereby increasing the susceptibility of diabetic patients to vascular complications.
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18
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Changes in Metabolic Regulation and the Microbiota Composition after Supplementation with Different Fatty Acids in db/db Mice. INTERNATIONAL JOURNAL OF FOOD SCIENCE 2022; 2022:3336941. [PMID: 35036426 PMCID: PMC8759926 DOI: 10.1155/2022/3336941] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Accepted: 12/15/2021] [Indexed: 12/20/2022]
Abstract
Introduction The effects of fatty acids on health vary and depend on the type, amount, and route of consumption. EPA and DHA have a defined role in health, unlike coconut oil. Objective The aim was to investigate the changes in metabolic regulation and the composition of the culture-dependent microbiota after supplementation with different fatty acids in db/db mice. Material and Methods. We were using 32 8-week-old db/db mice, supplemented for eight weeks with EPA/DHA derived from microalgae as well as coconut oil. The lipid, hormonal profiles, and composition of the culture-dependent microbiota and the phylogenetic analysis based on the 16S rRNA gene sequencing were determined for identification of the intestinal microbiota. Results Enriched diet with EPA/DHA reduced TNF-α, C-peptide, insulin resistance, resistin, and the plasma atherogenic index, but increased TC, LDL-c, VLDL-c, and TG without changes in HDL-c. Coconut oil raised the HDL-c, GIP, and TNF-α, with TG, insulin resistance, adiponectin, and C-peptide reduced. Conclusion The most abundant microbial populations were Firmicutes and the least Proteobacteria. EPA/DHA derived from microalgae contributes to improving the systemic inflammatory status, but depressed the diversity of the small intestine microbiota. Coconut oil only decreased the C-peptide, raising TNF-α, with an unfavorable hormonal and lipid profile.
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19
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Sottili M, Filardi T, Cantini G, Cosmi L, Morano S, Luconi M, Lenzi A, Crescioli C. Human cell-based anti-inflammatory effects of rosiglitazone. J Endocrinol Invest 2022; 45:105-114. [PMID: 34170488 DOI: 10.1007/s40618-021-01621-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 06/17/2021] [Indexed: 12/20/2022]
Abstract
PURPOSE The C-X-C motif chemokine ligand 10 (CXCL10) participates in diabetes and diabetic cardiomyopathy development from the early stages. Rosiglitazone (RGZ) exhibits anti-inflammatory properties and can target cardiomyocytes secreting CXCL10, under interferon (IFN)γ and tumor necrosis factor (TNF)α challenge. Cardiomyocyte remodeling, CD4 + T cells and dendritic cells (DCs) significantly contribute to the inflammatory milieu underlying and promoting disease development. We aimed to study the effect of RGZ onto inflammation-induced secretion of CXCL10, IFNγ, TNFα, interleukin (IL)-6 and IL-8 by human CD4 + T and DCs, and onto IFNγ/TNFα-dependent signaling in human cardiomyocytes associated with chemokine release. METHODS Cells maintained within an inflammatory-like microenvironment were exposed to RGZ at near therapy dose (5 µM). ELISA quantified cytokine secretion; qPCR measured mRNA expression; Western blot analyzed protein expression and activation; immunofluorescent analysis detected intracellular IFNγ/TNFα-dependent trafficking. RESULTS In human CD4 + T cells and DCs, RGZ inhibited CXCL10 release likely with a transcriptional mechanism, and reduced TNFα only in CD4 + T cells. In human cardiomyocytes, RGZ impaired IFNγ/TNFα signal transduction, blocking the phosphorylation/nuclear translocation of signal transducer and activator of transcription 1 (Stat1) and nuclear factor-kB (NF-kB), in association with a significant decrease in CXCL10 expression, IL-6 and IL-8 release. CONCLUSION As the combination of Th1 biomarkers like CXCL10, IL-8, IL-6 with classical cardiovascular risk factors seems to improve the accuracy in predicting T2D and coronary events, future studies might be desirable to further investigate the anti-Th1 effect of RGZ.
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Affiliation(s)
- M Sottili
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini 6, 50139, Florence, Italy
| | - T Filardi
- Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena 324, 00161, Rome, Italy
| | - G Cantini
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini 6, 50139, Florence, Italy
- DENOTHE Center of Excellence for Research, Transfer and High Education, University of Florence, 50139, Florence, Italy
| | - L Cosmi
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - S Morano
- Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena 324, 00161, Rome, Italy
| | - M Luconi
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini 6, 50139, Florence, Italy
- DENOTHE Center of Excellence for Research, Transfer and High Education, University of Florence, 50139, Florence, Italy
- Istituto Nazionale Biostrutture E Biosistemi (INBB), viale delle Medaglie d'Oro 305, 00136, Rome, Italy
| | - A Lenzi
- Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena 324, 00161, Rome, Italy
| | - C Crescioli
- Department of Movement, Human and Health Sciences, Section of Health Sciences, University of Rome "Foro Italico", Piazza L. de Bosis 6, 00135, Rome, Italy.
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20
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Ali H, Alterki A, Sindhu S, Alahmad B, Hammad M, Al-Sabah S, Alghounaim M, Jamal MH, Aldei A, Mairza MJ, Husain M, Deverajan S, Ahmad R, Cherian P, Alkhairi I, Alkandari A, Abubaker J, Abu-Farha M, Al-Mulla F. Robust Antibody Levels in Both Diabetic and Non-Diabetic Individuals After BNT162b2 mRNA COVID-19 Vaccination. Front Immunol 2021; 12:752233. [PMID: 34899701 PMCID: PMC8652288 DOI: 10.3389/fimmu.2021.752233] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 11/02/2021] [Indexed: 12/15/2022] Open
Abstract
The emergence of effective vaccines for COVID-19 has been welcomed by the world with great optimism. Given their increased susceptibility to COVID-19, the question arises whether individuals with type-2 diabetes mellitus (T2DM) and other metabolic conditions can respond effectively to the mRNA-based vaccine. We aimed to evaluate the levels of anti-SARS-CoV-2 IgG and neutralizing antibodies in people with T2DM and/or other metabolic risk factors (hypertension and obesity) compared to those without. This study included 262 people (81 diabetic and 181 non-diabetic persons) that took two doses of BNT162b2 (Pfizer–BioNTech) mRNA vaccine. Both T2DM and non-diabetic individuals had a robust response to vaccination as demonstrated by their high antibody titers. However, both SARS-CoV-2 IgG and neutralizing antibodies titers were lower in people with T2DM. The mean ( ± 1 standard deviation) levels were 154 ± 49.1 vs. 138 ± 59.4 BAU/ml for IgG and 87.1 ± 11.6 vs. 79.7 ± 19.5% for neutralizing antibodies in individuals without diabetes compared to those with T2DM, respectively. In a multiple linear regression adjusted for individual characteristics, comorbidities, previous COVID-19 infection, and duration since second vaccine dose, diabetics had 13.86 BAU/ml (95% CI: 27.08 to 0.64 BAU/ml, p=0.041) less IgG antibodies and 4.42% (95% CI: 8.53 to 0.32%, p=0.036) fewer neutralizing antibodies than non-diabetics. Hypertension and obesity did not show significant changes in antibody titers. Taken together, both type-2 diabetic and non-diabetic individuals elicited strong immune responses to SARS-CoV-2 BNT162b2 mRNA vaccine; nonetheless, lower levels were seen in people with diabetes. Continuous monitoring of the antibody levels might be a good indicator to guide personalized needs for further booster shots to maintain adaptive immunity. Nonetheless, it is important that people get their COVID-19 vaccination especially people with diabetes.
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Affiliation(s)
- Hamad Ali
- Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Health Sciences Center (HSC), Kuwait University, Jabriya, Kuwait.,Department of Genetics and Bioinformatics, Dasman Diabetes Institute (DDI), Dasman, Kuwait
| | - Abdulmohsen Alterki
- Department of Otolaryngology, Head, and Neck Surgery, Zain and Al-Sabah Hospitals, Ministry of Health, Kuwait City, Kuwait.,Medical Division, Dasman Diabetes Institute (DDI), Dasman, Kuwait
| | - Sardar Sindhu
- Department of Immunology and Microbiology, Dasman Diabetes Institute (DDI), Dasman, Kuwait.,Animal & Imaging Core Facility, Dasman Diabetes Institute (DDI), Dasman, Kuwait
| | - Barrak Alahmad
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, United States
| | - Maha Hammad
- Department of Biochemistry and Molecular Biology, Dasman Diabetes Institute (DDI), Dasman, Kuwait
| | - Salman Al-Sabah
- COVID-19 Research Group, Jaber Al-Ahmad Al-Sabah Hospital, Kuwait City, Kuwait
| | - Mohammad Alghounaim
- COVID-19 Research Group, Jaber Al-Ahmad Al-Sabah Hospital, Kuwait City, Kuwait
| | - Mohammad H Jamal
- COVID-19 Research Group, Jaber Al-Ahmad Al-Sabah Hospital, Kuwait City, Kuwait
| | - Ali Aldei
- Rheumatology Unit, Department of Medicine, Amiri Hospital, Kuwait City, Kuwait
| | - Mohammad J Mairza
- Department of Internal Medicine, Amiri Hospital, Kuwait City, Kuwait
| | - Maitham Husain
- Planning and Follow-Up Department, Ministry of Health, Kuwait City, Kuwait
| | - Sriraman Deverajan
- National Dasman Diabetes Biobank, Dasman Diabetes Institute (DDI), Dasman, Kuwait
| | - Rasheed Ahmad
- Department of Immunology and Microbiology, Dasman Diabetes Institute (DDI), Dasman, Kuwait
| | - Preethi Cherian
- Department of Biochemistry and Molecular Biology, Dasman Diabetes Institute (DDI), Dasman, Kuwait
| | - Irina Alkhairi
- Department of Biochemistry and Molecular Biology, Dasman Diabetes Institute (DDI), Dasman, Kuwait
| | - Abdullah Alkandari
- Department of Genetics and Bioinformatics, Dasman Diabetes Institute (DDI), Dasman, Kuwait
| | - Jehad Abubaker
- Department of Biochemistry and Molecular Biology, Dasman Diabetes Institute (DDI), Dasman, Kuwait
| | - Mohamed Abu-Farha
- Department of Biochemistry and Molecular Biology, Dasman Diabetes Institute (DDI), Dasman, Kuwait
| | - Fahd Al-Mulla
- Department of Genetics and Bioinformatics, Dasman Diabetes Institute (DDI), Dasman, Kuwait
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21
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Koleck TA, Topaz M, Tatonetti NP, George M, Miaskowski C, Smaldone A, Bakken S. Characterizing shared and distinct symptom clusters in common chronic conditions through natural language processing of nursing notes. Res Nurs Health 2021; 44:906-919. [PMID: 34637147 PMCID: PMC8641786 DOI: 10.1002/nur.22190] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 09/14/2021] [Accepted: 09/21/2021] [Indexed: 01/08/2023]
Abstract
Data-driven characterization of symptom clusters in chronic conditions is essential for shared cluster detection and physiological mechanism discovery. This study aims to computationally describe symptom documentation from electronic nursing notes and compare symptom clusters among patients diagnosed with four chronic conditions-chronic obstructive pulmonary disease (COPD), heart failure, type 2 diabetes mellitus, and cancer. Nursing notes (N = 504,395; 133,977 patients) were obtained for the 2016 calendar year from a single medical center. We used NimbleMiner, a natural language processing application, to identify the presence of 56 symptoms. We calculated symptom documentation prevalence by note and patient for the corpus. Then, we visually compared documentation for a subset of patients (N = 22,657) diagnosed with COPD (n = 3339), heart failure (n = 6587), diabetes (n = 12,139), and cancer (n = 7269) and conducted multiple correspondence analysis and hierarchical clustering to discover underlying groups of patients who have similar symptom profiles (i.e., symptom clusters) for each condition. As expected, pain was the most frequently documented symptom. All conditions had a group of patients characterized by no symptoms. Shared clusters included cardiovascular symptoms for heart failure and diabetes; pain and other symptoms for COPD, diabetes, and cancer; and a newly-identified cognitive and neurological symptom cluster for heart failure, diabetes, and cancer. Cancer (gastrointestinal symptoms and fatigue) and COPD (mental health symptoms) each contained a unique cluster. In summary, we report both shared and distinct, as well as established and novel, symptom clusters across chronic conditions. Findings support the use of electronic health record-derived notes and NLP methods to study symptoms and symptom clusters to advance symptom science.
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Affiliation(s)
- Theresa A. Koleck
- School of Nursing, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Maxim Topaz
- School of Nursing, Columbia University, New York, New York
- Data Science Institute, Columbia University, New York, New York
| | - Nicholas P. Tatonetti
- Data Science Institute, Columbia University, New York, New York
- Department of Biomedical Informatics, Columbia University, New York, New York
- Department of Systems Biology, Columbia University, New York, New York
- Department of Medicine, Columbia University, New York, New York
- Institute for Genomic Medicine, Columbia University, New York, New York
| | - Maureen George
- School of Nursing, Columbia University, New York, New York
| | - Christine Miaskowski
- School of Nursing, University of California San Francisco, San Francisco, California
| | - Arlene Smaldone
- School of Nursing, Columbia University, New York, New York
- College of Dental Medicine, Columbia University, New York, New York
| | - Suzanne Bakken
- School of Nursing, Columbia University, New York, New York
- Data Science Institute, Columbia University, New York, New York
- Department of Biomedical Informatics, Columbia University, New York, New York
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Vasishta S, Umakanth S, Adiga P, Joshi MB. Extrinsic and intrinsic factors influencing metabolic memory in type 2 diabetes. Vascul Pharmacol 2021; 142:106933. [PMID: 34763098 DOI: 10.1016/j.vph.2021.106933] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 10/18/2021] [Accepted: 11/04/2021] [Indexed: 12/24/2022]
Abstract
Direct and indirect influence of pathological conditions in Type 2 Diabetes (T2D) on vasculature manifests in micro and/or macro vascular complications that act as a major source of morbidity and mortality. Although preventive therapies exist to control hyperglycemia, diabetic subjects are always at risk to accrue vascular complications. One of the hypotheses explained is 'glycemic' or 'metabolic' memory, a process of permanent epigenetic change in different cell types whereby diabetes associated vascular complications continue despite glycemic control by antidiabetic drugs. Epigenetic mechanisms including DNA methylation possess a strong influence on the association between environment and gene expression, thus indicating its importance in the pathogenesis of a complex disease such as T2D. The vascular system is more prone to environmental influences and present high flexibility in response to physiological and pathological challenges. DNA methylation based epigenetic changes during metabolic memory are influenced by sustained hyperglycemia, inflammatory mediators, gut microbiome composition, lifestyle modifications and gene-nutrient interactions. Hence, understanding underlying mechanisms in manifesting vascular complications regulated by DNA methylation is of high clinical importance. The review provides an insight into various extrinsic and intrinsic factors influencing the regulation of DNA methyltransferases contributing to the pathogenesis of vascular complications during T2D.
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Affiliation(s)
- Sampara Vasishta
- Department of Ageing Research, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Shashikiran Umakanth
- Department of Medicine, Dr. T.M.A. Pai Hospital, Manipal Academy of Higher Education, Udupi 576101, Karnataka, India
| | - Prashanth Adiga
- Department of Reproductive Medicine and Surgery (MARC), Kasturba Hospital, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Manjunath B Joshi
- Department of Ageing Research, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India.
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Liu ZJ, Yan YJ, Weng HL, Ding HG. Type 2 diabetes mellitus increases liver transplant-free mortality in patients with cirrhosis: A systematic review and meta-analysis. World J Clin Cases 2021; 9:5514-5525. [PMID: 34307604 PMCID: PMC8281398 DOI: 10.12998/wjcc.v9.i20.5514] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 04/27/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The impact of type 2 diabetes mellitus (T2DM) on the prognosis and complications of liver cirrhosis is not fully clarified. AIM To clarify the mortality and related risk factors as well as complications in cirrhotic patients with T2DM. METHODS We searched PubMed, EMBASE, and the Cochrane Library from their inception to December 1, 2020 for cohort studies comparing liver transplant-free mortality, hepatocellular carcinoma (HCC), ascites, spontaneous bacterial peritonitis (SBP), variceal bleeding, and hepatic encephalopathy (HE) in cirrhotic patients with vs without T2DM. Odds ratios (ORs) were combined by using fixed-effects or random-effects models with RevMan software. RESULTS The database search generated a total of 17 cohort studies that met the inclusion criteria. Among these studies, eight reported the risk of mortality, and eight reported the risk of HCC. Three studies provided SBP rates, and two documented ascites rates. Four articles focused on HE rates, and three focused on variceal bleeding rates. Meta-analysis indicated that T2DM was significantly associated with an increased risk of liver transplant-free mortality [OR: 1.28, 95% confidence intervals (CI): 1.16-1.41, P < 0.0001] and HCC incidence (OR: 1.82, 95%CI: 1.32-2.51, P = 0.003). The risk of SBP was not significantly increased (OR: 1.16 95%CI: 0.86-1.57, P = 0.34). Additionally, T2DM did not significantly increase HE (OR: 1.31 95%CI: 0.97-1.77, P = 0.08), ascites (OR: 1.11 95%CI: 0.84-1.46, P = 0.46), and variceal bleeding (OR: 1.34, 95%CI: 0.99-1.82, P = 0.06). CONCLUSION The findings suggest that cirrhotic patients with T2DM have a poor prognosis and high risk of HCC. T2DM may not be associated with an increased risk of SBP, variceal bleeding, ascites, or HE in cirrhotic patients with T2DM.
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Affiliation(s)
- Zi-Jin Liu
- Department of Gastroenterology and Hepatology, Beijing You’an Hospital Affiliated to Capital Medical University, Beijing 100069, China
| | - Yi-Jie Yan
- Department of Gastroenterology and Hepatology, Beijing You’an Hospital Affiliated to Capital Medical University, Beijing 100069, China
| | - Hong-Lei Weng
- Department of Medicine II, Section Molecular Hepatology, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany
| | - Hui-Guo Ding
- Department of Gastroenterology and Hepatology, Beijing You’an Hospital Affiliated to Capital Medical University, Beijing 100069, China
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Babaei M, Alizadeh-Fanalou S, Nourian A, Yarahmadi S, Farahmandian N, Nabi-Afjadi M, Alipourfard I, Bahreini E. Evaluation of testicular glycogen storage, FGF21 and LDH expression and physiological parameters of sperm in hyperglycemic rats treated with hydroalcoholic extract of Securigera Securidaca seeds, and Glibenclamide. Reprod Biol Endocrinol 2021; 19:104. [PMID: 34233693 PMCID: PMC8262065 DOI: 10.1186/s12958-021-00794-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 06/25/2021] [Indexed: 12/16/2022] Open
Abstract
Structural and physiological changes in sperm and semen parameters reduce fertility in diabetic patients. Securigera Securidaca (S. Securidaca) seed is a herbal medicine with hypoglycemic, antioxidant, and anti-hypertensive effects. The question now is whether this herbal medicine improves fertility in diabetic males. The study aimed to evaluate the effects of hydroalcoholic extract of S. Securidaca seeds (HESS), glibenclamide and a combination of both on fertility in hyperglycemic rats by comparing histological and some biochemical changes in testicular tissue and sperm parameters. The treatment protocol included administration of three doses of HESS and one dose of glibenclamide, as well as treatment with both in diabetic Wistar diabetic rats and comparison of the results with untrated groups. The quality of the testicular tissue as well as histometric parameters and spermatogenesis indices were evaluated during histopathological examination. Epididymal sperm analysis including sperm motility, viability, abnormalities, maturity, and chromatin structure were studied. The effect of HESS on the expression of LDH and FGF21 genes and tissue levels of glycogen, lactate, and total antioxidant capacity in testicular tissue was investigated and compared with glibenclamide. HESS improved sperm parameters in diabetic rats but showed little restorative effect on damaged testicular tissue. In this regard, glibenclamide was more effective than the highest dose of HESS and its combination with HESS enhanced its effectiveness so that histological tissue characteristics and sperm parameters were were comparable to those of healthy rats. The expression level of testicular FGF21 gene increased in diabetic rats, which intensified after treatment with HESS as well as glibenclamide. The combination of HESS and glibenclamide restored the expression level of testicular LDH gene, as well as tissue storage of glycogen, lactate and LDH activity, and serum testosterone to the levels near healthy control. S. Securidaca seeds can be considered as an effective supplement in combination with hypoglycemic drugs to prevent infertility complications in diabetes.
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Affiliation(s)
- Mohammad Babaei
- grid.411807.b0000 0000 9828 9578Department of Clinical Sciences, Faculty of V, eterinary Science, Bu-Ali Sina University, Hamedan, Iran
| | - Shahin Alizadeh-Fanalou
- grid.411746.10000 0004 4911 7066Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Alireza Nourian
- grid.411807.b0000 0000 9828 9578Department of Pathobiology, Faculty of Veterinary Science, Bu-Ali Sina University, Hamedan, Iran
| | - Sahar Yarahmadi
- grid.411746.10000 0004 4911 7066Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Navid Farahmandian
- grid.411746.10000 0004 4911 7066Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mohsen Nabi-Afjadi
- grid.412266.50000 0001 1781 3962Department of Biochemistry, Faculty of Biological Science, Tarbiat Modares University, Tehran, Iran
| | - Iraj Alipourfard
- grid.11866.380000 0001 2259 4135Institute of Biology, Biotechnology and Environmental Protection, Faculty of Natural Sciences, University of Silesia, Bankowa 9, 40-007 Katowice, Poland
| | - Elham Bahreini
- grid.411746.10000 0004 4911 7066Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
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25
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Jukić I, Kolobarić N, Stupin A, Matić A, Kozina N, Mihaljević Z, Mihalj M, Šušnjara P, Stupin M, Ćurić ŽB, Selthofer-Relatić K, Kibel A, Lukinac A, Kolar L, Kralik G, Kralik Z, Széchenyi A, Jozanović M, Galović O, Medvidović-Kosanović M, Drenjančević I. Carnosine, Small but Mighty-Prospect of Use as Functional Ingredient for Functional Food Formulation. Antioxidants (Basel) 2021; 10:1037. [PMID: 34203479 PMCID: PMC8300828 DOI: 10.3390/antiox10071037] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 06/18/2021] [Accepted: 06/22/2021] [Indexed: 11/17/2022] Open
Abstract
Carnosine is a dipeptide synthesized in the body from β-alanine and L-histidine. It is found in high concentrations in the brain, muscle, and gastrointestinal tissues of humans and is present in all vertebrates. Carnosine has a number of beneficial antioxidant properties. For example, carnosine scavenges reactive oxygen species (ROS) as well as alpha-beta unsaturated aldehydes created by peroxidation of fatty acid cell membranes during oxidative stress. Carnosine can oppose glycation, and it can chelate divalent metal ions. Carnosine alleviates diabetic nephropathy by protecting podocyte and mesangial cells, and can slow down aging. Its component, the amino acid beta-alanine, is particularly interesting as a dietary supplement for athletes because it increases muscle carnosine, and improves effectiveness of exercise and stimulation and contraction in muscles. Carnosine is widely used among athletes in the form of supplements, but rarely in the population of cardiovascular or diabetic patients. Much less is known, if any, about its potential use in enriched food. In the present review, we aimed to provide recent knowledge on carnosine properties and distribution, its metabolism (synthesis and degradation), and analytical methods for carnosine determination, since one of the difficulties is the measurement of carnosine concentration in human samples. Furthermore, the potential mechanisms of carnosine's biological effects in musculature, metabolism and on immunomodulation are discussed. Finally, this review provides a section on carnosine supplementation in the form of functional food and potential health benefits and up to the present, neglected clinical use of carnosine.
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Affiliation(s)
- Ivana Jukić
- Department of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia; (I.J.); (N.K.); (A.S.); (A.M.); (N.K.); (Z.M.); (M.M.); (P.Š.); (M.S.); (A.K.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia; (Ž.B.Ć.); (K.S.-R.); (A.L.); (L.K.); (G.K.); (Z.K.); (A.S.); (M.J.); (O.G.); (M.M.-K.)
| | - Nikolina Kolobarić
- Department of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia; (I.J.); (N.K.); (A.S.); (A.M.); (N.K.); (Z.M.); (M.M.); (P.Š.); (M.S.); (A.K.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia; (Ž.B.Ć.); (K.S.-R.); (A.L.); (L.K.); (G.K.); (Z.K.); (A.S.); (M.J.); (O.G.); (M.M.-K.)
| | - Ana Stupin
- Department of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia; (I.J.); (N.K.); (A.S.); (A.M.); (N.K.); (Z.M.); (M.M.); (P.Š.); (M.S.); (A.K.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia; (Ž.B.Ć.); (K.S.-R.); (A.L.); (L.K.); (G.K.); (Z.K.); (A.S.); (M.J.); (O.G.); (M.M.-K.)
- Department of Pathophysiology, Physiology and Immunology, Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Cara Hadrijana 10E, HR-31000 Osijek, Croatia
| | - Anita Matić
- Department of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia; (I.J.); (N.K.); (A.S.); (A.M.); (N.K.); (Z.M.); (M.M.); (P.Š.); (M.S.); (A.K.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia; (Ž.B.Ć.); (K.S.-R.); (A.L.); (L.K.); (G.K.); (Z.K.); (A.S.); (M.J.); (O.G.); (M.M.-K.)
| | - Nataša Kozina
- Department of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia; (I.J.); (N.K.); (A.S.); (A.M.); (N.K.); (Z.M.); (M.M.); (P.Š.); (M.S.); (A.K.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia; (Ž.B.Ć.); (K.S.-R.); (A.L.); (L.K.); (G.K.); (Z.K.); (A.S.); (M.J.); (O.G.); (M.M.-K.)
| | - Zrinka Mihaljević
- Department of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia; (I.J.); (N.K.); (A.S.); (A.M.); (N.K.); (Z.M.); (M.M.); (P.Š.); (M.S.); (A.K.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia; (Ž.B.Ć.); (K.S.-R.); (A.L.); (L.K.); (G.K.); (Z.K.); (A.S.); (M.J.); (O.G.); (M.M.-K.)
| | - Martina Mihalj
- Department of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia; (I.J.); (N.K.); (A.S.); (A.M.); (N.K.); (Z.M.); (M.M.); (P.Š.); (M.S.); (A.K.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia; (Ž.B.Ć.); (K.S.-R.); (A.L.); (L.K.); (G.K.); (Z.K.); (A.S.); (M.J.); (O.G.); (M.M.-K.)
- Department of Dermatology and Venereology, University Hospital Osijek, HR-31000 Osijek, Croatia
| | - Petar Šušnjara
- Department of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia; (I.J.); (N.K.); (A.S.); (A.M.); (N.K.); (Z.M.); (M.M.); (P.Š.); (M.S.); (A.K.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia; (Ž.B.Ć.); (K.S.-R.); (A.L.); (L.K.); (G.K.); (Z.K.); (A.S.); (M.J.); (O.G.); (M.M.-K.)
| | - Marko Stupin
- Department of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia; (I.J.); (N.K.); (A.S.); (A.M.); (N.K.); (Z.M.); (M.M.); (P.Š.); (M.S.); (A.K.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia; (Ž.B.Ć.); (K.S.-R.); (A.L.); (L.K.); (G.K.); (Z.K.); (A.S.); (M.J.); (O.G.); (M.M.-K.)
- Department for Cardiovascular Disease, University Hospital Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia
| | - Željka Breškić Ćurić
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia; (Ž.B.Ć.); (K.S.-R.); (A.L.); (L.K.); (G.K.); (Z.K.); (A.S.); (M.J.); (O.G.); (M.M.-K.)
- Department of Internal Medicine, General Hospital Vinkovci, Zvonarska 57, HR-32100 Vinkovci, Croatia
| | - Kristina Selthofer-Relatić
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia; (Ž.B.Ć.); (K.S.-R.); (A.L.); (L.K.); (G.K.); (Z.K.); (A.S.); (M.J.); (O.G.); (M.M.-K.)
- Department for Cardiovascular Disease, University Hospital Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia
- Department for Internal Medicine, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia
| | - Aleksandar Kibel
- Department of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia; (I.J.); (N.K.); (A.S.); (A.M.); (N.K.); (Z.M.); (M.M.); (P.Š.); (M.S.); (A.K.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia; (Ž.B.Ć.); (K.S.-R.); (A.L.); (L.K.); (G.K.); (Z.K.); (A.S.); (M.J.); (O.G.); (M.M.-K.)
- Department for Cardiovascular Disease, University Hospital Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia
| | - Anamarija Lukinac
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia; (Ž.B.Ć.); (K.S.-R.); (A.L.); (L.K.); (G.K.); (Z.K.); (A.S.); (M.J.); (O.G.); (M.M.-K.)
- Department of Rheumatology, Clinical Immunology and Allergology, Clinical Hospital Center Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia
| | - Luka Kolar
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia; (Ž.B.Ć.); (K.S.-R.); (A.L.); (L.K.); (G.K.); (Z.K.); (A.S.); (M.J.); (O.G.); (M.M.-K.)
- Department of Internal Medicine, Vukovar General Hospital, HR-32000 Vukovar, Croatia
| | - Gordana Kralik
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia; (Ž.B.Ć.); (K.S.-R.); (A.L.); (L.K.); (G.K.); (Z.K.); (A.S.); (M.J.); (O.G.); (M.M.-K.)
- Nutricin j.d.o.o. Darda, HR-31326 Darda, Croatia
| | - Zlata Kralik
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia; (Ž.B.Ć.); (K.S.-R.); (A.L.); (L.K.); (G.K.); (Z.K.); (A.S.); (M.J.); (O.G.); (M.M.-K.)
- Department of Animal Production and Biotechnology, Faculty of Agrobiotechnical Sciences, Josip Juraj Strossmayer University of Osijek, Vladimira Preloga 1, HR-31000 Osijek, Croatia
| | - Aleksandar Széchenyi
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia; (Ž.B.Ć.); (K.S.-R.); (A.L.); (L.K.); (G.K.); (Z.K.); (A.S.); (M.J.); (O.G.); (M.M.-K.)
- Department of Chemistry, Josip Juraj Strossmayer University of Osijek, Cara Hadrijana 8/A, HR-31000 Osijek, Croatia
| | - Marija Jozanović
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia; (Ž.B.Ć.); (K.S.-R.); (A.L.); (L.K.); (G.K.); (Z.K.); (A.S.); (M.J.); (O.G.); (M.M.-K.)
- Department of Chemistry, Josip Juraj Strossmayer University of Osijek, Cara Hadrijana 8/A, HR-31000 Osijek, Croatia
| | - Olivera Galović
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia; (Ž.B.Ć.); (K.S.-R.); (A.L.); (L.K.); (G.K.); (Z.K.); (A.S.); (M.J.); (O.G.); (M.M.-K.)
- Department of Chemistry, Josip Juraj Strossmayer University of Osijek, Cara Hadrijana 8/A, HR-31000 Osijek, Croatia
| | - Martina Medvidović-Kosanović
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia; (Ž.B.Ć.); (K.S.-R.); (A.L.); (L.K.); (G.K.); (Z.K.); (A.S.); (M.J.); (O.G.); (M.M.-K.)
- Department of Chemistry, Josip Juraj Strossmayer University of Osijek, Cara Hadrijana 8/A, HR-31000 Osijek, Croatia
| | - Ines Drenjančević
- Department of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia; (I.J.); (N.K.); (A.S.); (A.M.); (N.K.); (Z.M.); (M.M.); (P.Š.); (M.S.); (A.K.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia; (Ž.B.Ć.); (K.S.-R.); (A.L.); (L.K.); (G.K.); (Z.K.); (A.S.); (M.J.); (O.G.); (M.M.-K.)
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Dowey R, Iqbal A, Heller SR, Sabroe I, Prince LR. A Bittersweet Response to Infection in Diabetes; Targeting Neutrophils to Modify Inflammation and Improve Host Immunity. Front Immunol 2021; 12:678771. [PMID: 34149714 PMCID: PMC8209466 DOI: 10.3389/fimmu.2021.678771] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 05/10/2021] [Indexed: 12/16/2022] Open
Abstract
Chronic and recurrent infections occur commonly in both type 1 and type 2 diabetes (T1D, T2D) and increase patient morbidity and mortality. Neutrophils are professional phagocytes of the innate immune system that are critical in pathogen handling. Neutrophil responses to infection are dysregulated in diabetes, predominantly mediated by persistent hyperglycaemia; the chief biochemical abnormality in T1D and T2D. Therapeutically enhancing host immunity in diabetes to improve infection resolution is an expanding area of research. Individuals with diabetes are also at an increased risk of severe coronavirus disease 2019 (COVID-19), highlighting the need for re-invigorated and urgent focus on this field. The aim of this review is to explore the breadth of previous literature investigating neutrophil function in both T1D and T2D, in order to understand the complex neutrophil phenotype present in this disease and also to focus on the development of new therapies to improve aberrant neutrophil function in diabetes. Existing literature illustrates a dual neutrophil dysfunction in diabetes. Key pathogen handling mechanisms of neutrophil recruitment, chemotaxis, phagocytosis and intracellular reactive oxygen species (ROS) production are decreased in diabetes, weakening the immune response to infection. However, pro-inflammatory neutrophil pathways, mainly neutrophil extracellular trap (NET) formation, extracellular ROS generation and pro-inflammatory cytokine generation, are significantly upregulated, causing damage to the host and perpetuating inflammation. Reducing these proinflammatory outputs therapeutically is emerging as a credible strategy to improve infection resolution in diabetes, and also more recently COVID-19. Future research needs to drive forward the exploration of novel treatments to improve infection resolution in T1D and T2D to improve patient morbidity and mortality.
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Affiliation(s)
- Rebecca Dowey
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom
| | - Ahmed Iqbal
- Sheffield Teaching Hospitals National Health Service (NHS) Foundation Trust, Sheffield, United Kingdom
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, United Kingdom
| | - Simon R. Heller
- Sheffield Teaching Hospitals National Health Service (NHS) Foundation Trust, Sheffield, United Kingdom
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, United Kingdom
| | - Ian Sabroe
- Sheffield Teaching Hospitals National Health Service (NHS) Foundation Trust, Sheffield, United Kingdom
| | - Lynne R. Prince
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom
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Abstract
It is recognized that a balance of different cytokines (synergistic versus antagonistic cytokines) determines the outcome in regulation of different actions such as inflammation, polarization, and secretion of macrophages, induction and secretion of T helper cells, and angiogenesis. It is also known that cytokine secretion is highly variable between individuals. These facts red flag the practice of only comparing absolute values of 1 or 2 cytokines in various studies. It is recognized that ratios of opposing functions yield better quantification of the equilibrium than just observing single values. It is the purpose of this article to (1) emphasize the need to measure a combination of cytokines selected in a manner so that ratios of these may be derived to yield more information about the homeostasis in body and (2) to offer a list of synergistic and antagonistic cytokines from which future investigators may select for more meaningful results.
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Affiliation(s)
- Prince Johnson Samuel
- Department of Physiology, Chettinad Academy of Research and Education, Chennai, India
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Huang X, Bao L, Tang X, Shen J, Ni X, Shen Y. Association between body mass index and effectiveness of continuous positive airway pressure in patients with obstructive sleep apnea: a retrospective study. Sleep Breath 2020; 24:1075-1081. [PMID: 31741135 DOI: 10.1007/s11325-019-01960-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 10/04/2019] [Accepted: 10/08/2019] [Indexed: 11/24/2022]
Abstract
PURPOSE Ineffective use of continuous positive airway pressure (CPAP) therapy can result in inconvenience and additional costs in patients with obstructive sleep apnea (OSA). This study investigated the predictive value of body mass index (BMI) to assess the efficacy of CPAP in patients with OSA. METHODS Data were extracted from a retrospective study performed in Silkeborg Hospital. The primary outcome was the improvement of Apnea-Hypopnea Index (AHI) after CPAP treatment. Association between BMI and improvement of AHI was assessed by multivariable linear regression. Interactions between BMI, baseline AHI severity (≥ 30 or < 30), and diabetes were also evaluated. RESULTS Four hundred eighty-one patients were included in the study. After adjusting for confounders, high BMI (coefficient [coef], 0.80; 95% confidence interval [CI], 0.59-1.00; p < 0.001) and high AHI severity (AHI ≥ 30) (coef, 29.2; 95% CI, 26.7-31.7; p < 0.001) were associated with greater improvement of AHI after CPAP treatment, while diabetes was associated with less improvement of AHI (coef, - 4.91; 95% CI, - 9.40 to - 0.42; p = 0.032). Baseline AHI severity, diabetes, and BMI showed significant interactions (p < 0.001). On subgroup analysis, the association between BMI and improvement of AHI remained significant only in patients belonging to high AHI severity subgroup (coef, 1.18; 95% CI, 0.8-1.49; p < 0.001) and that without diabetes (coef, 1.42; 95% CI, 1.11-1.72; p < 0.001). CONCLUSIONS Patients with OSA having high BMI, without diabetes, are more likely to benefit from CPAP therapy. Future studies should explore the predictors of the efficacy of CPAP in more depth.
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Affiliation(s)
- Xinmei Huang
- Department of Otolaryngology, Zheda Hospital of Zhejiang University, No. 38 Zheda Road, Hangzhou, 310000, People's Republic of China
| | - Liyan Bao
- Department of Hematology, Cixi People's Hospital, Cixi, Zhejiang, People's Republic of China
| | - Xuxia Tang
- Department of Otolaryngology, Zhejiang TCM Hospital, No. 54 Youdian Road, Hangzhou, 310000, People's Republic of China
| | - Jun Shen
- Department of Otolaryngology, Jinhua TCM Hospital, No. 439 Shuangxi West Road, Jinhua, 310000, People's Republic of China
| | - Xupei Ni
- Department of Otolaryngology, Jinhua TCM Hospital, No. 439 Shuangxi West Road, Jinhua, 310000, People's Republic of China
| | - Yanfei Shen
- Department of Intensive Care, Zhejiang Hospital, No. 12 Linyin Road, Hangzhou, Zhejiang, 310000, People's Republic of China.
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Mehnati P, Baradaran B, Vahidian F, Nadiriazam S. Functional response difference between diabetic/normal cancerous patients to inflammatory cytokines and oxidative stresses after radiotherapy. Rep Pract Oncol Radiother 2020; 25:730-737. [PMID: 32684862 DOI: 10.1016/j.rpor.2020.06.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Accepted: 06/23/2020] [Indexed: 02/06/2023] Open
Abstract
Diabetes, which is considered as a chronic metabolic disorder leads to an increase in inflammatory cytokines and oxidative stresses. Studies have shown several functional differences in the oxidative stress and inflammatory cytokines responses in diabetic/normal cancerous patients candidate for radiotherapy. Also, radiotherapy as a cancer treatment modality is known as a carcinogen due to oxidative damage via generation of reactive oxygen metabolites and also causing inflammation of the tissue by increasing the inflammatory cytokines. Therefore, the consequence of diabetes on oxidative stress and increased inflammatory factors and synergistic effects of radiotherapy on these factors cause complications in diabetics undergoing radiotherapy. It is considered as one of the most interesting objectives to control inflammation and oxidative stress in these patients. This review aims to concentrate on the influence of factors such as MPO, MDA, IL-1β, and TNF-α in diabetic patients by emphasizing the effects related to radiation-induced toxicity and inflammation by proposing therapeutic approaches which could be helpful in reduction of the complications.
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Affiliation(s)
- Parinaz Mehnati
- Department of Medical Physics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Vahidian
- Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sousan Nadiriazam
- Department of Medical Physics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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da Silva CB, Vieira DA, de Melo LF, Chagas ALS, Gomes AD, Faria Jr CLLD, Teixeira R, de Magalhães Queiroz DM, Rocha GA, Soares MMS, Bezerra JMT, Silva LD. Interleukin-6-174G/C polymorphism is associated with a decreased risk of type 2 diabetes in patients with chronic hepatitis C virus. World J Hepatol 2020; 12:137-148. [PMID: 32685106 PMCID: PMC7336292 DOI: 10.4254/wjh.v12.i4.137] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Revised: 02/28/2020] [Accepted: 03/22/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Chronic hepatitis C (CHC) is associated with type 2 diabetes mellitus. Although the pathogenesis remains to be elucidated, a growing evidence has suggested a role of pro-inflammatory immune response. Increased serum concentrations of Interleukin 6 (IL-6) have been associated with insulin resistance, type 2 diabetes mellitus as well as advanced forms of liver disease in chronic hepatitis C infection.
AIM To investigate the frequency of IL-6-174G/C (rs1800795) single nucleotide polymorphism (SNP) in CHC patients and in healthy subjects of the same ethnicity. Associations between type 2 diabetes mellitus (dependent variable) and demographic, clinical, nutritional, virological and, IL-6 genotyping data were also investigated in CHC patients.
METHODS Two hundred and forty-five patients with CHC and 179 healthy control subjects (blood donors) were prospectively included. Type 2 diabetes mellitus was diagnosed according to the criteria of the American Diabetes Association. Clinical, biochemical, histological and radiological methods were used for the diagnosis of the liver disease. IL-6 polymorphism was evaluated by Taqman SNP genotyping assay. The data were analysed by logistic regression models.
RESULTS Type 2 diabetes mellitus, blood hypertension and liver cirrhosis were observed in 20.8% (51/245), 40.0% (98/245) and 38.4% (94/245) of the patients, respectively. The frequency of the studied IL-6 SNP did not differ between the CHC patients and controls (P = 0.81) and all alleles were in Hardy-Weinberg equilibrium (P = 0.38). In the multivariate analysis, type 2 diabetes mellitus was inversely associated with GC and CC genotypes of IL-6-174 (OR = 0.42; 95%CI = 0.22-0.78; P = 0.006) and positively associated with blood hypertension (OR = 5.56; 95%CI = 2.79-11.09; P < 0.001).
CONCLUSION This study was the first to show that GC and CC genotypes of IL-6-174 SNP are associated with a decreased risk of type 2 diabetes mellitus in patients chronically infected with hepatitis C virus. The identification of potential inflammatory mediators involved in the crosstalk between hepatitis C virus and the axis pancreas-liver remains important issues that deserve further investigations.
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Affiliation(s)
- Cliviany Borges da Silva
- Sciences Applied to Adult Health Care Post-Graduate Programme, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Diego Alves Vieira
- Medical undergraduate student, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Luisa Freitas de Melo
- Medical undergraduate student, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Anna Luiza Soares Chagas
- Medical undergraduate student, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Adriana Dias Gomes
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - César Lúcio Lopes de Faria Jr
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Rosângela Teixeira
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
- Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Dulciene Maria de Magalhães Queiroz
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Gifone Aguiar Rocha
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Maria Marta Sarquis Soares
- Division of Endocrinology, Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Juliana Maria Trindade Bezerra
- Epidemiology of Infectious and Parasitic Diseases Laboratory, Department of Parasitology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Luciana Diniz Silva
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
- Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
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Yaribeygi H, Sathyapalan T, Atkin SL, Sahebkar A. Molecular Mechanisms Linking Oxidative Stress and Diabetes Mellitus. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:8609213. [PMID: 32215179 PMCID: PMC7085395 DOI: 10.1155/2020/8609213] [Citation(s) in RCA: 362] [Impact Index Per Article: 72.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/02/2019] [Revised: 12/07/2019] [Accepted: 02/04/2020] [Indexed: 12/15/2022]
Abstract
Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disorder characterized by chronic hyperglycemia and an inadequate response to circulatory insulin by peripheral tissues resulting in insulin resistance. Insulin resistance has a complex pathophysiology, and it is contributed to by multiple factors including oxidative stress. Oxidative stress refers to an imbalance between free radical production and the antioxidant system leading to a reduction of peripheral insulin sensitivity and contributing to the development of T2DM via several molecular mechanisms. In this review, we present the molecular mechanisms by which the oxidative milieu contributes to the pathophysiology of insulin resistance and diabetes mellitus.
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Affiliation(s)
- Habib Yaribeygi
- Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran
| | - Thozhukat Sathyapalan
- Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull HU3 2JZ, UK
| | | | - Amirhossein Sahebkar
- Halal Research Center of IRI, FDA, Tehran, Iran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Araújo LS, da Silva MV, da Silva CA, Borges MDF, Palhares HMDC, Rocha LP, Corrêa RRM, Rodrigues Júnior V, dos Reis MA, Machado JR. Analysis of serum inflammatory mediators in type 2 diabetic patients and their influence on renal function. PLoS One 2020; 15:e0229765. [PMID: 32130282 PMCID: PMC7055870 DOI: 10.1371/journal.pone.0229765] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Accepted: 02/14/2020] [Indexed: 02/07/2023] Open
Abstract
Aim To evaluate the serum concentrations of inflammatory mediators in patients with type 2 diabetes mellitus (T2DM) with or without renal alteration (RA) function. Methods Serum samples from 76 patients with T2DM and 24 healthy individuals were selected. Patients with T2DM were divided into two groups according to eGFR (> or < 60mL/min/1.73m2). Cytokines, chemokines and adipokines levels were evaluated using the Multiplex immunoassay and ELISA. Results TNFR1 and leptin were higher in the T2DM group with RA than in the T2DM group without RA and control group. All patients with T2DM showed increased resistin, IL-8, and MIP-1α compared to the control group. Adiponectin were higher and IL-4 decreased in the T2DM group with RA compared to the control group. eGFR positively correlated with IL-4 and negatively with TNFR1, TNFR2, and leptin in patients with T2DM. In the T2DM group with RA, eGFR was negatively correlated with TNFR1 and resistin. TNFR1 was positively correlated with resistin and leptin, as well as resistin with IL-8 and leptin. Conclusion Increased levels of TNFR1, adipokines, chemokines and decrease of IL-4 play important role in the inflammatory process developed in T2DM and decreased renal function. We also suggest that TNFR1 is a strong predictor of renal dysfunction in patients with T2DM.
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Affiliation(s)
- Liliane Silvano Araújo
- Discipline of General Pathology, Institute of Biological and Natural Sciences of Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil
| | - Marcos Vinícius da Silva
- Department of Microbiology, Immunology and Parasitology, Institute of Biological and Natural Sciences of Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil
| | - Crislaine Aparecida da Silva
- Discipline of General Pathology, Institute of Biological and Natural Sciences of Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil
| | - Maria de Fátima Borges
- Discipline of Endocrinology and Metabolism, Health Sciences Institute of Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil
| | - Heloísa Marcelina da Cunha Palhares
- Discipline of Endocrinology and Metabolism, Health Sciences Institute of Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil
| | - Laura Penna Rocha
- Discipline of General Pathology, Institute of Biological and Natural Sciences of Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil
| | - Rosana Rosa Miranda Corrêa
- Discipline of General Pathology, Institute of Biological and Natural Sciences of Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil
| | - Virmondes Rodrigues Júnior
- Department of Microbiology, Immunology and Parasitology, Institute of Biological and Natural Sciences of Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil
| | - Marlene Antônia dos Reis
- Discipline of General Pathology, Institute of Biological and Natural Sciences of Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil
| | - Juliana Reis Machado
- Discipline of General Pathology, Institute of Biological and Natural Sciences of Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil
- * E-mail:
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Pingali U, Ali MA, Gundagani S, Nutalapati C. Evaluation of the Effect of an Aqueous Extract of Azadirachta indica (Neem) Leaves and Twigs on Glycemic Control, Endothelial Dysfunction and Systemic Inflammation in Subjects with Type 2 Diabetes Mellitus - A Randomized, Double-Blind, Placebo-Controlled Clinical Study. Diabetes Metab Syndr Obes 2020; 13:4401-4412. [PMID: 33244247 PMCID: PMC7683773 DOI: 10.2147/dmso.s274378] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Accepted: 09/26/2020] [Indexed: 12/14/2022] Open
Abstract
PURPOSE Neem tree (Azadirachta indica) offers different bioactives ranging from pesticides to therapeutic molecules, depending on which part of the plant is used and the extraction methodology and the solvent used. This study was aimed at evaluating the safety and efficacy of a standardized aqueous extract of Azadirachta indica leaves and twigs (NEEM) on glycemic control, endothelial dysfunction, and systemic inflammation in patients with type 2 diabetes mellitus (T2DM). METHODS In this randomized, double-blind, placebo-controlled clinical study (RCT), 80 T2DM subjects, who have already been on standard metformin therapy, received either 125 mg, 250 mg, 500 mg of NEEM or placebo twice daily for 12 weeks. Postprandial blood sugar level (PPBS), fasting blood sugar level (FBS), glycosylated hemoglobin (HbA1c), insulin resistance (IR), endothelial function, oxidative stress, systemic inflammation, IL-6 and TNF-α, platelet aggregation and lipid profile were assessed. Adverse drug reactions, if any, were noted. GraphPad Prism 8 was used to perform statistical analysis. RESULTS NEEM at the doses of 125, 250, and 500 mg BID significantly reduced PPBS (from 194.4±14 to 173.1±12.8mg/dL, 192.3±17.1 to 161.8±9.7mg/dL, and 205.9±7.2 to 159.3±7.1mg/dL, respectively), FBS (from 119.2±5.0 to 109.2±5.7mg/dL, 115.5±4.4 to 103.7±4.2mg/dL, and 120.7±4.2 to 97.3±3.7mg/dL, respectively), HbA1c (from 6.87 ± 0.4% to 6.64 ± 0.4%, 7.52 ± 0.4% to 6.86 ± 0.3%, and 7.78 ± 0.2% to 6.26 ± 0.4%, respectively), and IR (from 4.5 ± 1.2 to 3.4 ± 0.9, 3.8 ± 1.1 to 2.5 ± 0.6, and 4.6 ± 1.3 to 2.0 ± 0.6, respectively) compared to placebo. Also, NEEM significantly improved endothelial function, decreased oxidative stress and systemic inflammation compared to placebo. The efficacy was significant with all the doses, but no effect on platelet aggregation or lipid profile was observed. CONCLUSION NEEM may significantly ameliorate hyperglycemia, endothelial dysfunction, and systemic inflammation, on top of what metformin could do, in subjects with T2DM.
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Affiliation(s)
- Usharani Pingali
- Department of Pharmacology and Therapeutics, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana500073, India
- Correspondence: Usharani Pingali Email
| | - Mohammed Abid Ali
- Department of Pharmacology and Therapeutics, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana500073, India
| | - Srinivas Gundagani
- Department of Pharmacology and Therapeutics, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana500073, India
| | - Chandrasekhar Nutalapati
- Department of Pharmacology and Therapeutics, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana500073, India
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Wang Z, Ni X, Zhang L, Sun L, Zhu X, Zhou Q, Yang Z, Yuan H. Toll-Like Receptor 4 and Inflammatory Micro-Environment of Pancreatic Islets in Type-2 Diabetes Mellitus: A Therapeutic Perspective. Diabetes Metab Syndr Obes 2020; 13:4261-4272. [PMID: 33204132 PMCID: PMC7666984 DOI: 10.2147/dmso.s279104] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 10/20/2020] [Indexed: 12/13/2022] Open
Abstract
Patients with type-2 diabetes mellitus (T2DM) display chronic low-grade inflammation induced by activation of the innate immune system. Toll-like receptor (TLR)4 is a pattern recognition receptor that plays a vital part in activation of the innate immune system. Results from animal and computer-simulation studies have demonstrated that targeting TLR4 to block the TLR4-nuclear factor-kappa B (NF-κB) pathway reduces the inflammatory response and complications associated with T2DM. Therefore, TLR4-targeted therapy has broad prospects. Here, we reviewed the role of TLR4 in inflammation during chronic hyperglycemia in T2DM and its therapeutic prospects.
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Affiliation(s)
- Zhaoping Wang
- The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China
| | - Xiaolin Ni
- The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China
| | - Li Zhang
- The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China
| | - Liang Sun
- The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China
| | - Xiaoquan Zhu
- The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China
| | - Qi Zhou
- The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China
| | - Ze Yang
- The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China
| | - Huiping Yuan
- The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China
- Correspondence: Huiping Yuan The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Dongdan DaHua Road 1#, Beijing100730, People’s Republic of ChinaTel +86-10-58115043Fax +86-10-65237929 Email
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França FL, Honorio-França AC, Honorio MS, Silva FHD, Fujimori M, França EL, Araújo FGDS. Dental implant surfaces treated with phosphoric acid can modulate cytokine production by blood MN cells. Braz Oral Res 2019; 33:e040. [PMID: 31508724 DOI: 10.1590/1807-3107bor-2019.vol33.0040] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Accepted: 04/09/2019] [Indexed: 11/22/2022] Open
Abstract
The study characterizes dental implant surfaces treated with phosphoric acid to assess the effects of acid treatment on blood cells and correlate them with cytokine levels. The implant surfaces examined were divided into untreated metal surface (US; n = 50), metal surface treated with phosphoric acid (ATS; n = 50) and cement surface (CS; n = 50) groups. The samples were characterized by scanning electron microscopy (SEM) and rheometry. The implants were incubated with human blood mononuclear cells for 24 h, with surface rinsing in the ATS treatment. Cell viability was determined by colorimetric methods and cytokines in the culture supernatant were quantified using flow cytometry. In the ATS group, the surface porosity and contact surface were increased and plaques were observed on the surface. The blood flow and viscosity curves were similar among the treatments, and the high cell viability rates indicate the biocompatibility of the materials used. An increase in the levels of IL-2, IL-4, IL-6, IL-10 and TNF-α was observed in the ATS and CS groups. There were positive correlations between IL-10 and IL-2 levels and between IL-10 and IL-4 levels in the culture supernatant of the ATS group. The results suggest that implant surface treatment with phosphoric acid activates the production of inflammatory cytokines. The increased cytokine levels can modulate the immune response, thereby improving biofunctional processes and promoting the success of dental implants.
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Affiliation(s)
- Fernando Luzía França
- Program of Materials Engineering, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil
| | | | - Mariana Silva Honorio
- Institute of Biological and Health Science, Universidade Federal de Mato Grosso, Barra do Garças, MT, Brazil
| | - Fabiana Helen da Silva
- Institute of Biological and Health Science, Universidade Federal de Mato Grosso, Barra do Garças, MT, Brazil
| | - Mahmi Fujimori
- Institute of Biological and Health Science, Universidade Federal de Mato Grosso, Barra do Garças, MT, Brazil
| | - Eduardo Luzía França
- Institute of Biological and Health Science, Universidade Federal de Mato Grosso, Barra do Garças, MT, Brazil
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Zhang K, Yang J, Ao N, Jin S, Qi R, Shan F, Du J. Methionine enkephalin (MENK) regulates the immune pathogenesis of type 2 diabetes mellitus via the IL-33/ST2 pathway. Int Immunopharmacol 2019; 73:23-40. [PMID: 31078923 DOI: 10.1016/j.intimp.2019.04.054] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 04/25/2019] [Accepted: 04/25/2019] [Indexed: 12/18/2022]
Abstract
The incidence and mortality of type 2 diabetes mellitus (T2DM) rank among the top ten worldwide. Emerging studies indicate pathological roles for the immune system in inflammation, insulin resistance and islet β-cell damage in subjects with T2DM. Methionine enkephalin (MENK) is present in endocrine cells of the pancreas and has been suggested to be an important mediator between the immune and neuroendocrine systems. Therefore, it may play a role in modulating insulin secretion from islet cells. Since little is known about the effect of MENK on T2DM, therefore it was the aim of this study to characterize the role and possible mechanism of action of MENK on plasma glucose and serum insulin levels in T2DM rats and INS-1 cells in vivo and in vitro. MENK significantly decreased the plasma glucose level and increased the serum insulin concentration in T2DM rats. It also increased the serum levels of the cytokines IL-5 and IL-10, while decreased TNF-α and IL-2 levels. We further confirmed that MENK regulated glucose metabolism by upregulating opioid receptor expression and modulating the IL-33/ST2 and MyD88-TRAF6-NF-κB p65 signaling pathways. Based on these results, an intraperitoneal injection of MENK represents a potentially new approach for T2DM.
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Affiliation(s)
- Keying Zhang
- Department of Endocrinology, No. 4 Teaching Hospital, China Medical University, Shenyang 110032, China
| | - Jing Yang
- Department of Endocrinology, No. 4 Teaching Hospital, China Medical University, Shenyang 110032, China
| | - Na Ao
- Department of Endocrinology, No. 4 Teaching Hospital, China Medical University, Shenyang 110032, China
| | - Shi Jin
- Department of Endocrinology, No. 4 Teaching Hospital, China Medical University, Shenyang 110032, China
| | - Ruiqun Qi
- Department of Dermatology, No. 1 Teaching Hospital, China Medical University, Shenyang 110001, China
| | - Fengping Shan
- Department of Immunology, School of Basic Medical Science, China Medical University, Shenyang 110122, China
| | - Jian Du
- Department of Endocrinology, No. 4 Teaching Hospital, China Medical University, Shenyang 110032, China.
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Petrie JR, Guzik TJ, Touyz RM. Diabetes, Hypertension, and Cardiovascular Disease: Clinical Insights and Vascular Mechanisms. Can J Cardiol 2018; 34:575-584. [PMID: 29459239 PMCID: PMC5953551 DOI: 10.1016/j.cjca.2017.12.005] [Citation(s) in RCA: 1009] [Impact Index Per Article: 144.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2017] [Revised: 12/06/2017] [Accepted: 12/07/2017] [Indexed: 12/11/2022] Open
Abstract
Hypertension and type 2 diabetes are common comorbidities. Hypertension is twice as frequent in patients with diabetes compared with those who do not have diabetes. Moreover, patients with hypertension often exhibit insulin resistance and are at greater risk of diabetes developing than are normotensive individuals. The major cause of morbidity and mortality in diabetes is cardiovascular disease, which is exacerbated by hypertension. Accordingly, diabetes and hypertension are closely interlinked because of similar risk factors, such as endothelial dysfunction, vascular inflammation, arterial remodelling, atherosclerosis, dyslipidemia, and obesity. There is also substantial overlap in the cardiovascular complications of diabetes and hypertension related primarily to microvascular and macrovascular disease. Common mechanisms, such as upregulation of the renin-angiotensin-aldosterone system, oxidative stress, inflammation, and activation of the immune system likely contribute to the close relationship between diabetes and hypertension. In this article we discuss diabetes and hypertension as comorbidities and discuss the pathophysiological features of vascular complications associated with these conditions. We also highlight some vascular mechanisms that predispose to both conditions, focusing on advanced glycation end products, oxidative stress, inflammation, the immune system, and microRNAs. Finally, we provide some insights into current therapies targeting diabetes and cardiovascular complications and introduce some new agents that may have vasoprotective therapeutic potential in diabetes.
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Affiliation(s)
- John R Petrie
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom
| | - Tomasz J Guzik
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom
| | - Rhian M Touyz
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom.
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Ghalandari H, Kamalpour M, Alimadadi A, Nasrollahzadeh J. Comparison of Two Calorie-Reduced Diets of Different Carbohydrate and Fiber Contents and a Simple Dietary Advice Aimed to Modify Carbohydrate Intake on Glycemic Control and Inflammatory Markers in Type 2 Diabetes: A Randomized Trial. Int J Endocrinol Metab 2018; 16:e12089. [PMID: 29696035 PMCID: PMC5903385 DOI: 10.5812/ijem.12089] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2017] [Revised: 10/23/2017] [Accepted: 11/28/2017] [Indexed: 01/06/2023] Open
Abstract
OBJECTIVES The aim of this study was to compare the effect of a simple dietary advice with two energy-restricted diets with different carbohydrate and fiber contents on anthropometric, biochemical, and inflammatory markers over an 8-wk intervention period in individuals with diabetes. METHODS Forty-seven patients with type 2 diabetes (31 women and 16 men; age: 52.9 ± 8.0 years, body mass index: 29.5 ± 4.9 kg.m-2) completed an 8-wk randomized intervention trial that compared a simple dietary advice aimed to modulate carbohydrate intake (n = 13) with the two calorie-restricted (CR) diets (25% caloric restriction from total energy requirements) differing with regard to carbohydrate and fiber content, one with higher fiber (CRHF) containing 55% energy from carbohydrate plus a tablespoon of psyllium powder (n = 18) and the other with lower carbohydrate (CRLC) containing 40% energy from carbohydrate plus placebo powder (n = 16). Weight, plasma concentrations of glucose, insulin, lipids, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) were determined at baseline and after 8 weeks. RESULTS The mean change of body weight and plasma lipids were not different between the groups. Fasting plasma insulin and the homeostasis model assessment of insulin resistance (HOMA-IR) were significantly lower in the CRHF group (changes from baseline values in simple advice, CRHF, and CRLC were 1.3 ± 1.9, -1.0 ± 1.2, and 0.3 ± 3.1 µIL/mL for insulin and 0.5 ± 0.7, -0.3 ± 0.6, and 0.2 ± 0.9 for HOMA-IR, respectively). The levels of IL-6 significantly decreased in the CRHF and CRLC groups (changes from baseline values in simple advice, CRHF, and CRLC were 7.5 ± 6.8, -1.2 ± 4.7, and -4.2 ± 5.6 pg/mL, respectively). TNF-α levels were significantly lower only in the CRHF compared to the advice group (P < 0.05). CONCLUSIONS Our results suggest that in comparison with simple advice to modify carbohydrate intake, a calorie-restricted, moderate carbohydrate diet supplemented with psyllium has better effects on plasma insulin and pro-inflammatory cytokines in patients with type 2 diabetes.
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Affiliation(s)
- Hamid Ghalandari
- MSc, Department of Clinical Nutrition and Dietetics, National Nutrition, and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Mahdieh Kamalpour
- MSc, Department of Clinical Nutrition and Dietetics, National Nutrition, and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Ashraf Alimadadi
- MD, Department of Internal Medicine, Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Javad Nasrollahzadeh
- MSc, Department of Clinical Nutrition and Dietetics, National Nutrition, and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
- Corresponding author: Javad Nasrollahzadeh, Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, P.O. 19395-4741, Tehran, IR Iran. Tel: +98-2122357483, Fax: +98-2122360660, E-mail:
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Condorelli RA, La Vignera S, Mongioì LM, Alamo A, Calogero AE. Diabetes Mellitus and Infertility: Different Pathophysiological Effects in Type 1 and Type 2 on Sperm Function. Front Endocrinol (Lausanne) 2018; 9:268. [PMID: 29887834 PMCID: PMC5980990 DOI: 10.3389/fendo.2018.00268] [Citation(s) in RCA: 113] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Accepted: 05/08/2018] [Indexed: 11/25/2022] Open
Abstract
Although the prevalence of sub-infertility in diabetic patients in childbearing age is known, the mechanisms by which diabetes mellitus (DM) causes male infertility are not completely explained. This detrimental effect is achieved with a variety of mechanisms that include pre-testicular, testicular, and post-testicular pathogenetic moments and can be different in type 1 diabetes mellitus (DM1) and type 2 diabetes mellitus (DM2) patients because of type of diabetes, duration of disease, and glycemic metabolic compensation. Aim of this study was to evaluate whether diabetic disease can be considered a risk factor for infertility considering the etiopathogenetic differences between DM1 and DM2 on sperm function. We enrolled 38 DM1 patients and 55 DM2 patients with idiopathic infertility history >12 months, and 100 healthy fertile subjects. The following outcomes were evaluated in optical microscopy and flow cytometry: sperm function (by conventional and biofunctional sperm parameters) and signs of urogenital infection/inflammation (by sperm leukocyte concentrations and indices of oxidative stress). Moreover, an andrological evaluation (by didymo-epididymal ultrasound evaluation, serum total testosterone, LH, and FSH measurements) was performed in DM1 and DM2 patients compared to controls. Diabetic patients showed a higher risk of becoming infertile and the pathophysiological mechanisms of damage were different in DM1 and DM2. Conventional sperm parameters of diabetic patients are worse than controls (p < 0.05). The DM2 caused an inflammatory condition with increased oxidative stress resulting in decreased sperm vitality and increased sperm DNA fragmentation. DM1 altered epididymal voiding causing low ejaculate volume and mitochondrial damage resulting in decreased sperm motility. These findings and evidences support the contention that DM could be regarded as cause of male infertility suggesting that the prevention of diabetic disease in DM2 and the follow-up of seminal parameters in DM1 could prevent fertility decline in these categories of patients.
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Analysis of inflammatory cytokine and TLR expression levels in Type 2 Diabetes with complications. Sci Rep 2017; 7:7633. [PMID: 28794498 PMCID: PMC5550417 DOI: 10.1038/s41598-017-07230-8] [Citation(s) in RCA: 76] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Accepted: 06/23/2017] [Indexed: 12/29/2022] Open
Abstract
The pathogenesis and complications of type 2 diabetes (T2DM) are closely linked with defective glucose metabolism, obesity, cardiovascular disease and an inability to mount an effective immune response to certain pathogenic organisms. Perturbations in key innate immune receptors known as Toll-like receptors (TLRs) and inflammatory mediators such as IL-6, TNFα and IL-1β have been linked with T2DM. Herein, we sought to establish whether patients with T2DM and underlying complications exhibit perturbations in cytokine and TLR expression. Serum cytokine and mRNA levels of cytokines/TLRs in monocytes (M) and neutrophils (N) were measured in a cohort of 112 diabetic patients: good glycaemic control without complications (GC), good glycaemic control with complications (GCC), poor glycaemic control without complications (PC) and poor glycaemic control with complications (PCC) and compared them with 34 non-diabetic volunteers (NGT). Serum cytokine levels were normal in all study participants. In the GC group, cytokine and TLR gene expression were enhanced compared to NGT. In contrast, suppressed cytokine and TLR gene expression were evident in PC, GCC & PCC groups when compared to the GC. In conclusion, whereas serum pro-inflammatory cytokine levels are unaltered in T2DM patients, differences in inflammatory gene profiles exist among the T2DM patient groups.
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Nishikai-Yan Shen T, Kanazawa S, Kado M, Okada K, Luo L, Hayashi A, Mizuno H, Tanaka R. Interleukin-6 stimulates Akt and p38 MAPK phosphorylation and fibroblast migration in non-diabetic but not diabetic mice. PLoS One 2017; 12:e0178232. [PMID: 28542434 PMCID: PMC5441644 DOI: 10.1371/journal.pone.0178232] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Accepted: 05/03/2017] [Indexed: 12/12/2022] Open
Abstract
Persistent inflammatory environment and abnormal macrophage activation are characteristics of chronic diabetic wounds. Here, we attempted to characterize the differences in macrophage activation and temporal variations in cytokine expression in diabetic and non-diabetic wounds, with a focus on interleukin (IL)-6 mRNA expression and the p38 MAPK and PI3K/Akt signaling pathways. Cutaneous wound closure, CD68- and arginase-1 (Arg-1)-expressing macrophages, and cytokine mRNA expression were examined in non-diabetic and streptozotocin-induced type 1 diabetic mice at different time points after injury. The effect of IL-6 on p38 MAPK and Akt phosphorylation was investigated, and an in vitro scratch assay was performed to determine the role of IL-6 in primary skin fibroblast migration. Before injury, mRNA expression levels of the inflammatory markers iNOS, IL-6, and TNF-α were higher in diabetic mice; however, IL-6 expression was significantly lower 6 h post injury in diabetic wounds than that in non-diabetic wounds. Non-diabetic wounds exhibited increased p38 MAPK and Akt phosphorylation; however, no such increase was found in diabetic wounds. In fibroblasts from non-diabetic mice, IL-6 increased the phosphorylation of p38 MAPK and levels of its downstream factor CREB, and also significantly increased Akt phosphorylation and levels of its upstream factor P13K. These effects of IL-6 were not detected in fibroblasts derived from the diabetic mice. In scratch assays, IL-6 stimulated the migration of primary cultured skin fibroblasts from the non-diabetic mice, and the inhibition of p38 MAPK was found to markedly suppress IL-6–stimulated fibroblast migration. These findings underscore the critical differences between diabetic and non-diabetic wounds in terms of macrophage activation, cytokine mRNA expression profile, and involvement of the IL-6-stimulated p38 MAPK–Akt signaling pathway. Aberrant macrophage activation and abnormalities in the cytokine mRNA expression profile during different phases of wound healing should be addressed when designing effective therapeutic modalities for refractory diabetic wounds.
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MESH Headings
- Animals
- Antigens, CD/metabolism
- Antigens, Differentiation, Myelomonocytic/metabolism
- Cell Movement/drug effects
- Cell Movement/physiology
- Cells, Cultured
- Diabetes Mellitus, Experimental/metabolism
- Diabetes Mellitus, Experimental/pathology
- Diabetes Mellitus, Type 1/metabolism
- Diabetes Mellitus, Type 1/pathology
- Fibroblasts/drug effects
- Fibroblasts/metabolism
- Fibroblasts/pathology
- Interleukin-6/administration & dosage
- Interleukin-6/metabolism
- Macrophages/drug effects
- Macrophages/metabolism
- Macrophages/pathology
- Male
- Mice, Inbred C57BL
- Phosphorylation/drug effects
- Phosphorylation/physiology
- Proto-Oncogene Proteins c-akt/metabolism
- RNA, Messenger/metabolism
- Skin/drug effects
- Skin/metabolism
- Skin/pathology
- Wound Healing/drug effects
- Wound Healing/physiology
- p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors
- p38 Mitogen-Activated Protein Kinases/metabolism
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Affiliation(s)
- Tsubame Nishikai-Yan Shen
- Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Shigeyuki Kanazawa
- Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan
- Department of Plastic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Makiko Kado
- Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Kayoko Okada
- Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Lin Luo
- Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Ayato Hayashi
- Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Hiroshi Mizuno
- Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Rica Tanaka
- Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan
- * E-mail:
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Malik JA, Masoodi SR, Shoib S. Obstructive sleep apnea in Type 2 diabetes and impact of continuous positive airway pressure therapy on glycemic control. Indian J Endocrinol Metab 2017; 21:106-112. [PMID: 28217508 PMCID: PMC5240049 DOI: 10.4103/2230-8210.196005] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Obstructive sleep apnea (OSA) and type 2 diabetes mellitus (T2DM) are two interacting epidemics both with high prevalence and morbidity. Both epidemiologic and clinical studies suggest that the majority of patients with T2DM also have OSA and untreated OSA in these patients results in poor glycemic control leading to acceleration of diabetes-related complications. OBJECTIVES To assess the prevalence and severity of OSA in T2DM patients and to assess the impact of OSA treatment on presenting symptoms and hemoglobin A1c (HbA1c). METHODS We performed polysomnography (PSG) studies and measured HbA1c in 62 consecutive patients with T2DM that were referred from various subspecialty clinics from July 2011 to August 2013. RESULTS In our 62 diabetic patients, 59 (95.2%) had abnormal PSG. Based on Apnea-Hypopnea Index (AHI) score, 3 (5.1%) patients had mild, 28 (47.5%) had moderate, and 28 (47.5%) had severe OSA. The mean AHI of diabetic patients was significantly more than nondiabetic patients, i.e., 25.7 versus 19.7 (P = 0.001). Variables that significantly correlated with the presence of OSA include age, gender, body mass index (BMI), hypertension, diabetes, and cardiovascular disease (P < 0.05); however, on logistic regression only BMI, hypertension, and nocturia correlated with OSA. Overall, 59% of diabetic patients showed improvement in their glycemic control as measured by HbA1c with continuous positive airway pressure (CPAP) treatment. Significant, moderate, and mild categories of treatment response were respectively observed in 7%, 20%, and 32% of patients. CONCLUSION Treatment of OSA with CPAP reduces HbA1c in a significant number of diabetics.
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Affiliation(s)
- Javid Ahmad Malik
- Department of Pulmonary Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
| | - Shariq Rashid Masoodi
- Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
| | - Sheikh Shoib
- Department of Psychiatry, Government Medical College, Srinagar, Jammu and Kashmir, India
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Chakraborty K, Joy M. Anti-diabetic and anti-inflammatory activities of commonly available cephalopods. INTERNATIONAL JOURNAL OF FOOD PROPERTIES 2016. [DOI: 10.1080/10942912.2016.1217008] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
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Blocking Nuclear Factor-Kappa B Protects against Diet-Induced Hepatic Steatosis and Insulin Resistance in Mice. PLoS One 2016; 11:e0149677. [PMID: 26930600 PMCID: PMC4773172 DOI: 10.1371/journal.pone.0149677] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Accepted: 02/02/2016] [Indexed: 02/06/2023] Open
Abstract
Inflammation critically contributes to the development of various metabolic diseases. However, the effects of inhibiting inflammatory signaling on hepatic steatosis and insulin resistance, as well as the underlying mechanisms remain obscure. In the current study, male C57BL/6J mice were fed a chow diet or high-fat diet (HFD) for 8 weeks. HFD-fed mice were respectively treated with p65 siRNA, non-silence control siRNA or vehicle every 4th day for the last 4 weeks. Vehicle-treated (HF) and non-silence siRNA-treated (HFNS) mice displayed overt inflammation, hepatic steatosis and insulin resistance compared with chow-diet-fed (NC) mice. Upon treatment with NF-κB p65 siRNA, HFD-fed (HFPS) mice were protected from hepatic steatosis and insulin resistance. Furthermore, Atg7 and Beclin1 expressions and p-AMPK were increased while p-mTOR was decreased in livers of HFPS mice in relative to HF and HFNS mice. These results suggest a crosslink between NF-κB signaling pathway and liver AMPK/mTOR/autophagy axis in the context of hepatic steatosis and insulin resistance.
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Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human Skeletal Muscle Cells. Molecules 2015; 20:8242-69. [PMID: 25961164 PMCID: PMC6272652 DOI: 10.3390/molecules20058242] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Revised: 04/29/2015] [Accepted: 05/04/2015] [Indexed: 01/04/2023] Open
Abstract
Mitochondrial dysfunction and inflammation are widely accepted as key hallmarks of obesity-induced skeletal muscle insulin resistance. The aim of the present study was to evaluate the functional roles of an anti-inflammatory compound, celastrol, in mitochondrial dysfunction and insulin resistance induced by antimycin A (AMA) in human skeletal muscle cells. We found that celastrol treatment improved insulin-stimulated glucose uptake activity of AMA-treated cells, apparently via PI3K/Akt pathways, with significant enhancement of mitochondrial activities. Furthermore, celastrol prevented increased levels of cellular oxidative damage where the production of several pro-inflammatory cytokines in cultures cells was greatly reduced. Celastrol significantly increased protein phosphorylation of insulin signaling cascades with amplified expression of AMPK protein and attenuated NF-κB and PKC θ activation in human skeletal muscle treated with AMA. The improvement of insulin signaling pathways by celastrol was also accompanied by augmented GLUT4 protein expression. Taken together, these results suggest that celastrol may be advocated for use as a potential therapeutic molecule to protect against mitochondrial dysfunction-induced insulin resistance in human skeletal muscle cells.
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Joshi DV, Patil RR, Naik SR. Hydroalcohol extract of Trigonella foenum-graecum seed attenuates markers of inflammation and oxidative stress while improving exocrine function in diabetic rats. PHARMACEUTICAL BIOLOGY 2015; 53:201-211. [PMID: 25339548 DOI: 10.3109/13880209.2014.913296] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
CONTEXT AND OBJECTIVE The herb fenugreek, Trigonella foenum-graecum Linn (Fabaceae), seeds have been traditionally used in the treatment of diabetes but its effect on oxidative stress and pro-inflammatory cytokines in the improvement of exocrine function of diabetes has not been studied. The effect of hydroalcoholic extract of Trigonella foenum-graecum seeds (HEF) on alloxan-induced type-II diabetic rat model was investigated. MATERIALS AND METHODS Effect of HEF (500, 1000, and 2000 mg/kg), glimepiride (4 mg/kg), and combination of HEF (500 mg/kg) + glimepiride (2 mg/kg), on alloxan-induced diabetic rats was evaluated by assaying (blood glucose, serum protein, glycosylated hemoglobin, muscle and liver glycogen, glucose uptake by diaphragm, liver glucose transport, serum pancreatic enzymes (α-amylase, lipase), pro-inflammatory cytokines (TNF-α, IL-6), antioxidant enzymes [glutathione (GSH), superoxide dismutase (SOD)], lipid peroxides (liver and pancreas), and histoarchitecture (liver, pancreas). RESULTS Treatment with HEF (at different doses), glimepiride, and HEF + glimepiride increased body weight and glucose uptake, reduced plasma glucose, glycosylated hemoglobin, liver glucose transport, pro-inflammatory cytokines, pancreatic enzymes and restored depleted glycogen (muscle, liver) and total protein significantly (p < 0.01) and dose dependently, including prevention of lipid peroxidation and restoration of GSH and SOD (liver and pancreas). Treatment with HEF + glimepiride potentiated hypoglycemic activity of glimepiride. Histoarchitecture of liver and pancreas showed marked improvement. CONCLUSION Present experimental findings suggest that HEF possesses promising hypoglycemic activity, presumably by amelioration of oxidative stress and pro-inflammatory cytokines. HEF may be useful as an adjuvant with clinically effective antidiabetic drugs in the management of type-II diabetes.
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Affiliation(s)
- Deval V Joshi
- Department of Pharmacology, Sinhgad Institute of Pharmaceutical Science , Lonavala, Pune, Maharashtra , India
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Beneficial Effect of 7-O-Galloyl-D-sedoheptulose, a Polyphenol Isolated from Corni Fructus, against Diabetes-Induced Alterations in Kidney and Adipose Tissue of Type 2 Diabetic db/db Mice. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 2013:736856. [PMID: 24348717 PMCID: PMC3853307 DOI: 10.1155/2013/736856] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/02/2013] [Accepted: 09/07/2013] [Indexed: 02/07/2023]
Abstract
Traditional medicines are being focused on as possible treatments for diabetes and its complications because of their negligible toxic and/or side effects. In line with this, our group has reported that Corni Fructus, a traditional medicine considered exhibiting beneficial effects on liver and kidney functions, possessed an antidiabetic effect via ameliorating glucose-mediated metabolic disorders. To add to these findings, we screened the iridoid glycoside fraction containing morroniside and loganin, and low molecular weight polyphenol fraction containing 7-O-galloyl-d-sedoheptulose (GS) from Corni Fructus. To our knowledge, GS is a compound only detected in Corni Fructus, and its biological activity has been poorly understood until now. For these reasons, we examined whether GS has an ameliorative effect on diabetic changes using type 2 diabetic db/db mice. Our findings suggest that GS has a beneficial effect on the pathological state of the serum, kidney, and adipose tissue related to diabetic damage.
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Park CH, Tanaka T, Yokozawa T. Evaluation of 7-O-galloyl-d-sedoheptulose, isolated from Corni Fructus, in the adipose tissue of type 2 diabetic db/db mice. Fitoterapia 2013; 89:131-42. [DOI: 10.1016/j.fitote.2013.03.026] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2012] [Revised: 03/26/2013] [Accepted: 03/29/2013] [Indexed: 12/15/2022]
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Cheng KC, Asakawa A, Li YX, Liu IM, Amitani H, Cheng JT, Inui A. Opioid μ-receptors as new target for insulin resistance. Pharmacol Ther 2013; 139:334-40. [PMID: 23688574 DOI: 10.1016/j.pharmthera.2013.05.002] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2013] [Accepted: 04/12/2013] [Indexed: 10/26/2022]
Abstract
Type-2 diabetes is one of the fastest growing public health problems worldwide resulting from both environmental and genetic factors. Activation of μ-opioid receptor (MOR) could result in reversal of the impairment of insulin-stimulated glucose disposal in genetically obese Zucker rats via exercise training. This improvement of insulin resistance was associated with an elevation of circulating β-endorphin to ameliorate the post-receptor insulin signaling cascade, including downstream effectors of the phosphatidylinositol 3-kinase (PI3-kinase) signaling pathway. In insulin resistant rats, Loperamide treatment effected on the insulin receptor substrate (IRS)-1/PI3-kinase/Akt signaling cascade and subsequent insulin-stimulated glucose transport trafficking on skeletal muscle, which were all suppressed by MOR antagonism. In addition, induction of insulin resistance by the intake of high fructose is more rapid in MOR knockout mice than in wild-type mice. Improvements in insulin sensitivity through the peripheral MOR activation overcoming defects related to the post-receptor in IRS-1-associated PI3-kinase step have been defined. Opioid receptor activation, especially of the μ-subtype, may provide merits in the amelioration of defective insulin action. Atypical zeta (ζ) isoform of protein kinase C serves as a factor that integrates with peripheral MOR pathway and insulin signals for glucose utilization. The developments call new insights into the chemical compounds and/or herbal products that might enhance opioid peptide secretion and/or stimulate MOR in peripheral insulin-sensitive tissues to serve as potential agents or adjuvants for helping the glucose metabolism. In the present review, we update these topics and discuss the concept of targeting peripheral MOR pathway for the treatment of insulin resistance.
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Affiliation(s)
- Kai-Chun Cheng
- Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan
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Fibrinogen-like protein 2 expression correlates with microthrombosis in rats with type 2 diabetic nephropathy. J Biomed Res 2013; 25:120-7. [PMID: 23554679 PMCID: PMC3596703 DOI: 10.1016/s1674-8301(11)60015-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2010] [Revised: 11/07/2010] [Accepted: 01/11/2011] [Indexed: 12/21/2022] Open
Abstract
Fibrinogen-like protein 2 (fgl2), a novel prothrombinase, is involved in microthrombosis. We examined fgl2 expression in the glomerular and tubulointerstitial capillaries and its correlation with microthromsis in rats with streptozocin-induced type 2 diabetic nephropathy. Our RT-PCR and immunoblotting analysis showed that fgl2 mRNA and protein levels were increased in microvascular endothelial cells of the glomeruli and renal interstitia at week 19 and became significantly elevated with the development of diabetic nephropathy (P < 0.01). Fgl2 was not or only weakly expressed in the renal tissues of normal rats. Furthermore, a direct significant correlation (r = 0.543, P < 0.01) was found between fgl2 expression and microthrombotic capillaries in the renal tissues. Enzyme linked immunosorbent assays (ELISA) additionally showed that circulating TNF-α levels in rats with type 2 diabetes were significantly elevated and closely correlated with fgl2 expression (r = 0.871, P < 0.01). Our results suggest that fgl2 may activate renal microthrombosis, thus contributing to glomerular hypertension and renal ischemia.
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