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Cavalcante-Silva J, Koh TJ. Depletion of natural killer cells enhances wound healing in diabetic mice. J Leukoc Biol 2025; 117:qiaf044. [PMID: 40235157 PMCID: PMC12089793 DOI: 10.1093/jleuko/qiaf044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2025] [Revised: 02/21/2025] [Accepted: 04/15/2025] [Indexed: 04/17/2025] Open
Abstract
Natural killer cells are known for their killing function in infection- and tumor-related responses but also can shape immune responses involved in physiological processes such as wound healing. We recently reported that natural killer cells accumulate in skin wounds and express proinflammatory cytokines that may impede healing. Since impaired wound healing in diabetes is associated with persistent inflammation, the purpose of the present study was to determine whether natural killer cells contribute to impaired skin wound healing in diabetic mice. Here, we show that natural killer cells accumulate at higher levels in wounds in diabetic mice and exhibit less mature phenotypes compared to nondiabetic mice. In addition, local neutralization of CX3CL1 reduced natural killer cell accumulation in wounds of diabetic mice, suggesting that CX3CL1 plays a role in the infiltration of these cells to the wound site. Finally, depletion of natural killer cells in diabetic wounds improved reepithelization and collagen deposition, suggesting that the elevated levels of natural killer cells contribute to impaired healing associated with diabetes.
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Affiliation(s)
- Jacqueline Cavalcante-Silva
- Center for Wound Healing and Tissue Regeneration, University of Illinois at Chicago, Chicago, 60612-7246 Illinois, United States
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, 60612-7246 Illinois, United States
| | - Timothy J Koh
- Center for Wound Healing and Tissue Regeneration, University of Illinois at Chicago, Chicago, 60612-7246 Illinois, United States
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, 60612-7246 Illinois, United States
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Thong PM, Wong YH, Kornfeld H, Goletti D, Ong CWM. Immune dysregulation of diabetes in tuberculosis. Semin Immunol 2025; 78:101959. [PMID: 40267700 DOI: 10.1016/j.smim.2025.101959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 04/04/2025] [Accepted: 04/16/2025] [Indexed: 04/25/2025]
Abstract
The rising prevalence of diabetes mellitus (DM) is undermining global efforts to eliminate tuberculosis (TB). Most studies found that patients with pulmonary TB and DM have more cavitary lung lesions, higher mycobacterial burden on the lungs, longer periods of infectiousness, and worse outcomes. Both human and animal studies indicate that TB-DM is associated with impaired innate and adaptive immune responses, resulting in delayed bacterial clearance. Similar observations have been noted in other infections, such as those caused by Klebsiella pneumoniae, where DM contributes to increased susceptibility and worse outcomes due to compromised immune functions including defective phagocytosis and impaired early immune cell recruitment. This review delves into the mechanisms of immune dysfunction in TB-DM, exploring how DM increases TB susceptibility and severity. By elucidating these complex interactions, this review aims to offer insights into more effective strategies for managing and improving outcomes for patients with this challenging comorbidity.
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Affiliation(s)
- Pei Min Thong
- Infectious Diseases Translational Research Programme, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Yi Hao Wong
- Infectious Diseases Translational Research Programme, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Hardy Kornfeld
- Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Delia Goletti
- Translational Research Unit, Department of Epidemiology, National Institute for infectious diseases-IRCCS L. Spallanzani, Rome, Italy.
| | - Catherine W M Ong
- Infectious Diseases Translational Research Programme, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Infectious Diseases, Department of Medicine, National University Hospital, Singapore; Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore.
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Saadh MJ, Allela OQB, Kareem RA, Kyada A, Malathi H, Nathiya D, Bhanot D, Sameer HN, Hamad AK, Athab ZH, Adil M. Immune cell dysfunction: A critical player in development of diabetes complications. Curr Res Transl Med 2025; 73:103510. [PMID: 40339429 DOI: 10.1016/j.retram.2025.103510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 03/08/2025] [Accepted: 03/28/2025] [Indexed: 05/10/2025]
Abstract
Diabetes mellitus, a global health challenge, influences millions worldwide by leading to severe complications and premature death. A key factor in its pathogenesis is immune cell dysfunction, which aggravates both type 1 and type 2 diabetes. The important role that immune cell dysregulation plays in the emergence of diabetes complications is investigated in this research. It highlights the manner in which diabetes compromises the immune system's adaptive as well as innate responses. Key defects in innate immunity include impaired pathogen recognition, and dysfunctional behavior of macrophages, neutrophils, and natural killer (NK) cells. Additionally, the complement system is dysregulated, and cytokine production is altered, affecting overall immune signaling. The study investigates the dysfunction of several T and B cell subsets, such as CD4+ T cells, CD8+ T cells, regulatory T cells, and B cells, in relation to adaptive immunity. These dysfunctions collectively contribute to chronic inflammation, reduced pathogen clearance, and increased susceptibility to infections, ultimately exacerbating diabetes complications. Developing targeted therapies to reduce diabetes complications and enhance patient outcomes requires an understanding of these mechanisms.
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Affiliation(s)
- Mohamed J Saadh
- Faculty of Pharmacy, Middle East University, Amman, 11831, Jordan
| | | | | | - Ashishkumar Kyada
- Marwadi University Research Center, Department of Pharmacy, Faculty of Health Sciences, Marwadi University, Rajkot 360003, Gujarat, India
| | - H Malathi
- Department of Biotechnology and Genetics, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
| | - Deepak Nathiya
- Department of Pharmacy Practice, Institute of Pharmacy, NIMS University Rajasthan, Jaipur, India
| | - Deepak Bhanot
- Centre for Research Impact & Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, 140401, Punjab, India
| | - Hayder Naji Sameer
- Collage of Pharmacy, National University of Science and Technology, Dhi Qar, 64001, Iraq
| | | | - Zainab H Athab
- Department of Pharmacy, Al-Zahrawi University College, Karbala, Iraq
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Yang X, Li D, Chen Y, Zhang X, Zhao Q. Exploring the Link Between Diabetes, Herpes Zoster, and Post-Herpetic Neuralgia: Insights From Mendelian Randomization. J Pain Res 2025; 18:1479-1489. [PMID: 40144692 PMCID: PMC11937845 DOI: 10.2147/jpr.s501674] [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: 11/14/2024] [Accepted: 03/12/2025] [Indexed: 03/28/2025] Open
Abstract
Background Diabetes mellitus (DM), herpes zoster (HZ) and its sequelae, post-herpetic neuralgia (PHN), are common in elderly individuals. Previous observational studies have shown that the prevalence of HZ and PHN in conjunction with DM is increasing. Nonetheless, few studies have investigated the causal relationships between DM and the risk of HZ and PHN. Methods A two-sample Mendelian randomization (TSMR) analysis was conducted on genome-wide association study (GWAS) data. We obtained four separate datasets for DM: type 1 diabetes (T1D), type 2 diabetes (T2D), mother diabetes mellitus (mother-DM) and father diabetes mellitus (father-DM), and two independent datasets for HZ and anti-varicella-zoster virus IgG (VZV-IgG), a single GWAS for PHN. The inverse variance weighted (IVW), MR‒Egger, weighted median and weighted mode analyses were used to estimate the causality. Results Genetically predicted T1D increased the level of VZV-IgG (IVW: OR=1.011, 95% CI 1.006-1.016, P -FDR=8.44×10-6). T2D (IVW: OR=1.313; 95% CI 1.043-1.655, P -FDR=0.041), mother-DM (IVW: OR=7.909; 95% CI 1.232-50.777, P -FDR=0.039), and father-DM (IVW: OR=11.798; 95% CI 2.051-67.874, P -FDR=0.023) increased the risk of PHN. No reverse causality was found between HZ, PHN, and DM. Conclusion Our research reveals a causal link between genetically determined T1D and increased VZV-IgG levels. Additionally, genetically predicted T2D and a family history of DM increase the risk of PHN. These discoveries deepen our comprehension of the underlying causes of HZ and PHN.
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Affiliation(s)
- Xueying Yang
- Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, People’s Republic of China
| | - Dairui Li
- Department of Thyroid Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Yuqing Chen
- Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, People’s Republic of China
| | - Xuerong Zhang
- Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, People’s Republic of China
| | - Qiong Zhao
- Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, People’s Republic of China
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Schmitz T, Freuer D, Linseisen J, Meisinger C. Associations between blood markers of glucose metabolism and characteristics of circulating lymphocytes. Clin Nutr 2024; 43:285-295. [PMID: 39546924 DOI: 10.1016/j.clnu.2024.11.004] [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: 04/29/2024] [Revised: 10/28/2024] [Accepted: 11/03/2024] [Indexed: 11/17/2024]
Abstract
AIMS The pathophysiology of diabetes is not fully understood; recent research indicates close relations with immunological alterations. Therefore, the aim of this study was to investigate the associations between markers of glucose metabolism and characteristics of blood lymphocytes in a population-based cohort. METHODS The analysis was based on data from 219 non-diabetic participants of the MEGA study in Augsburg, Germany, who were recruited between 2018 and 2021. The majority of participants were examined two different times with a time lag of 9 months. Fasting venous blood samples were taken and oral glucose tolerance tests (OGTT) were performed at both visits. Immune cells were analyzed from fresh blood using flow cytometry. The associations between fasting blood glucose levels, glucose levels at 2 h after oral glucose bolus and glycated hemoglobin (HbA1c) concentrations and the quantity of different lymphocyte subsets were analyzed using linear mixed regression models with random intercept. P values were FDR-adjusted. RESULTS HbA1c was negatively associated with the marginal zone B cells (IgD + CD27+ B cells). Fasting glucose was positively associated with natural killer (NK) cells and 2-h OGTT glucose was positively associated with NKT cells. Finally, HbA1c showed significantly negative associations with the CD57-PD1-NKT cell subset. CONCLUSION Markers of glucose metabolism showed significant associations with B cell, NK cell and NKT cell subsets, which clearly indicates a relation between glucose metabolism and the adaptive immune system.
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Affiliation(s)
- T Schmitz
- Epidemiology, Medical Faculty, University of Augsburg, Stenglinstraße 2, 86156 Augsburg, Germany.
| | - D Freuer
- Epidemiology, Medical Faculty, University of Augsburg, Stenglinstraße 2, 86156 Augsburg, Germany
| | - J Linseisen
- Epidemiology, Medical Faculty, University of Augsburg, Stenglinstraße 2, 86156 Augsburg, Germany
| | - C Meisinger
- Epidemiology, Medical Faculty, University of Augsburg, Stenglinstraße 2, 86156 Augsburg, Germany
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Stanisavljevic I, Pavlovic S, Simovic Markovic B, Jurisevic M, Krajnovic T, Mijatovic S, Spasojevic M, Mitrovic S, Corovic I, Jovanovic I. Semaglutide decelerates the growth and progression of breast cancer by enhancing the acquired antitumor immunity. Biomed Pharmacother 2024; 181:117668. [PMID: 39536536 DOI: 10.1016/j.biopha.2024.117668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 10/31/2024] [Accepted: 11/07/2024] [Indexed: 11/16/2024] Open
Abstract
Semaglutide, a glucagon-like peptide 1 receptor agonist, is an antidiabetic that has recently shown promising immunomodulatory and antitumor effects. Breast cancer is the most common type of cancer affecting women worldwide. The aim of this study was to analyze the effects of semaglutide on the antitumor immunity in a 4T1 mouse breast cancer model. After induction of breast cancer, BALB/C mice were treated intraperitoneally with semaglutide. Semaglutide administration decelerated tumor appearance, growth and progression. The antidiabetic drug showed neither a direct cytotoxic effect in vitro, nor an angiogenic effect. Furthermore, depletion of NK cells had no affect on tumor growth in semaglutide treated mice suggesting a non-NK cell-dependent mechanism. However, semaglutide increased the accumulation and maturation of CD11c+ dendritic cell, while decreasing the percentage of FoxP3+ regulatory T cells in the spleen and primary tumor. In addition, semaglutide increased tumor infiltration and promoted the antitumor phenotype of T cells, in vivo. Furthermore, semaglutide enhanced the cytotoxic capacity of CD8+ T cells, in vitro. These results suggest that semaglutide enhances the acquired antitumor immune response and has potential for the future treatment of malignancies.
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Affiliation(s)
- Isidora Stanisavljevic
- Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, Kragujevac 34000, Serbia.
| | - Sladjana Pavlovic
- Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, Kragujevac 34000, Serbia.
| | - Bojana Simovic Markovic
- Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, Kragujevac 34000, Serbia.
| | - Milena Jurisevic
- Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, Kragujevac 34000, Serbia; Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, Kragujevac 34000, Serbia.
| | - Tamara Krajnovic
- Department of Immunology, Institute for Biological Research "Siniša Stanković"- National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, Belgrade 11108, Serbia.
| | - Sanja Mijatovic
- Department of Immunology, Institute for Biological Research "Siniša Stanković"- National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, Belgrade 11108, Serbia.
| | - Marija Spasojevic
- Department of Pathology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, Kragujevac 34000, Serbia.
| | - Slobodanka Mitrovic
- Department of Pathology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, Kragujevac 34000, Serbia.
| | - Irfan Corovic
- Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, Kragujevac 34000, Serbia; General Hospital of Novi Pazar, Department of Internal Medicine, Generala Živkovića 1, Novi Pazar 36300, Serbia.
| | - Ivan Jovanovic
- Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, Kragujevac 34000, Serbia.
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Bender M, Santos JM, Dufour JM, Deshmukh H, Trasti S, Elmassry MM, Shen CL. Peanut Shell Extract Improves Markers of Glucose Homeostasis in Diabetic Mice by Modulating Gut Dysbiosis and Suppressing Inflammatory Immune Response. Nutrients 2024; 16:4158. [PMID: 39683552 DOI: 10.3390/nu16234158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 11/22/2024] [Accepted: 11/26/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND/OBJECTIVE There is strong evidence that the tripartite interaction between glucose homeostasis, gut microbiota, and the host immune system plays a critical role in the pathophysiology of type 2 diabetes mellitus (T2DM). We reported previously that peanut shell extract (PSE) improves mitochondrial function in db/db mice by suppressing oxidative stress and inflammation in the liver, brain, and white adipose tissue. This study evaluated the impacts of PSE supplementation on glucose homeostasis, liver histology, intestinal microbiome composition, and the innate immune response in diabetic mice. METHODS Fourteen db/db mice were randomly assigned to a diabetic group (DM, AIN-93G diet) and a PSE group (1% wt/wt PSE in the AIN-93G diet) for 5 weeks. Six C57BL/6J mice received the AIN-93G diet for 5 weeks (control group). Parameters of glucose homeostasis included serum insulin, HOMA-IR, HOMA-B, and the analysis of pancreatic tissues for insulin and glucagon. We assessed the innate immune response in the colon and liver using a microarray. Gut microbiome composition of cecal contents was analyzed using 16S rRNA gene amplicon sequencing. RESULTS PSE supplementation improved glucose homeostasis (decreased serum insulin concentration, HOMA-IR, and HOMA-B) and reduced hepatic lipidosis in diabetic mice. PSE supplementation reversed DM-induced shifts in the relative abundance of amplicon sequence variants of Enterorhabdus, Staphylococcus, Anaerotruncus, and Akkermansia. Relative to the DM mice, the PSE group had suppressed gene expression levels of Cd8α, Csf2, and Irf23 and increased expression levels of Tyk2, Myd88, and Gusb in the liver. CONCLUSIONS This study demonstrates that PSE supplementation improves T2DM-associated disorders of diabetic mice, in part due to the suppression of innate immune inflammation.
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Affiliation(s)
- Matthew Bender
- Department of Medical Education, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - Julianna M Santos
- Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
- Department of Microanatomy and Cellular Biology, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA
| | - Jannette M Dufour
- Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
- Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
- Obesity Research Institute, Texas Tech University, Lubbock, TX 79401, USA
| | - Hemalata Deshmukh
- Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - Scott Trasti
- Laboratory Animal Resource Center, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - Moamen M Elmassry
- Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA
| | - Chwan-Li Shen
- Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
- Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
- Obesity Research Institute, Texas Tech University, Lubbock, TX 79401, USA
- Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
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Taranto D, Kloosterman DJ, Akkari L. Macrophages and T cells in metabolic disorder-associated cancers. Nat Rev Cancer 2024; 24:744-767. [PMID: 39354070 DOI: 10.1038/s41568-024-00743-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/16/2024] [Indexed: 10/03/2024]
Abstract
Cancer and metabolic disorders have emerged as major global health challenges, reaching epidemic levels in recent decades. Often viewed as separate issues, metabolic disorders are shown by mounting evidence to heighten cancer risk and incidence. The intricacies underlying this connection are still being unraveled and encompass a complex interplay between metabolites, cancer cells and immune cells within the tumour microenvironment (TME). Here, we outline the interplay between metabolic and immune cell dysfunction in the context of three highly prevalent metabolic disorders, namely obesity; two associated liver diseases, metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH); and type 2 diabetes. We focus primarily on macrophages and T cells, the critical roles of which in dictating inflammatory response and immune surveillance in metabolic disorder-associated cancers are widely reported. Moreover, considering the ever-increasing number of patients prescribed with metabolism disorder-altering drugs and diets in recent years, we discuss how these therapies modulate systemic and local immune phenotypes, consequently impacting cancer malignancy. Collectively, unraveling the determinants of metabolic disorder-associated immune landscape and their role in fuelling cancer malignancy will provide a framework essential to therapeutically address these highly prevalent diseases.
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Affiliation(s)
- Daniel Taranto
- Division of Tumour Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
- Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Daan J Kloosterman
- Division of Tumour Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
- Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Leila Akkari
- Division of Tumour Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
- Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
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Miceli G, Basso MG, Pennacchio AR, Cocciola E, Pintus C, Cuffaro M, Profita M, Rizzo G, Sferruzza M, Tuttolomondo A. The Potential Impact of SGLT2-I in Diabetic Foot Prevention: Promising Pathophysiologic Implications, State of the Art, and Future Perspectives-A Narrative Review. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1796. [PMID: 39596981 PMCID: PMC11596194 DOI: 10.3390/medicina60111796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 10/24/2024] [Accepted: 10/30/2024] [Indexed: 11/29/2024]
Abstract
The impact of diabetic foot (DF) on the healthcare system represents a major public health problem, leading to a considerable clinical and economic burden. The factors contributing to DF's development and progression are strongly interconnected, including metabolic causes, neuropathy, arteriopathy, and inflammatory changes. Sodium-glucose cotransporter 2 inhibitors (SGLT2-i), novel oral hypoglycemic drugs used as an adjunct to standard treatment, have recently changed the pharmacological management of diabetes. Nevertheless, data about the risk of limb amputation, discordant and limited to canagliflozin, which is currently avoided in the case of peripheral artery disease, have potentially discouraged the design of specific studies targeting DF. There is good evidence for the single immunomodulatory, neuroprotective, and beneficial vascular effects of SGLT2-i. Still, there is no clinical evidence about the early use of SGLT2-i in diabetic foot due to the lack of longitudinal and prospective studies proving the effect of these drugs without confounders. This narrative review aims to discuss the main evidence about the impact of SGLT2-i on the three complications of diabetes implicated in the development of DF, the state of the art, and the potential future implications.
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Affiliation(s)
- Giuseppe Miceli
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (M.G.B.); (A.R.P.); (E.C.); (C.P.); (M.C.); (M.P.); (G.R.); (M.S.); (A.T.)
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90127 Palermo, Italy
| | - Maria Grazia Basso
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (M.G.B.); (A.R.P.); (E.C.); (C.P.); (M.C.); (M.P.); (G.R.); (M.S.); (A.T.)
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90127 Palermo, Italy
| | - Andrea Roberta Pennacchio
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (M.G.B.); (A.R.P.); (E.C.); (C.P.); (M.C.); (M.P.); (G.R.); (M.S.); (A.T.)
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90127 Palermo, Italy
| | - Elena Cocciola
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (M.G.B.); (A.R.P.); (E.C.); (C.P.); (M.C.); (M.P.); (G.R.); (M.S.); (A.T.)
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90127 Palermo, Italy
| | - Chiara Pintus
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (M.G.B.); (A.R.P.); (E.C.); (C.P.); (M.C.); (M.P.); (G.R.); (M.S.); (A.T.)
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90127 Palermo, Italy
| | - Mariagiovanna Cuffaro
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (M.G.B.); (A.R.P.); (E.C.); (C.P.); (M.C.); (M.P.); (G.R.); (M.S.); (A.T.)
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90127 Palermo, Italy
| | - Martina Profita
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (M.G.B.); (A.R.P.); (E.C.); (C.P.); (M.C.); (M.P.); (G.R.); (M.S.); (A.T.)
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90127 Palermo, Italy
| | - Giuliana Rizzo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (M.G.B.); (A.R.P.); (E.C.); (C.P.); (M.C.); (M.P.); (G.R.); (M.S.); (A.T.)
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90127 Palermo, Italy
| | - Mariachiara Sferruzza
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (M.G.B.); (A.R.P.); (E.C.); (C.P.); (M.C.); (M.P.); (G.R.); (M.S.); (A.T.)
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90127 Palermo, Italy
| | - Antonino Tuttolomondo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (M.G.B.); (A.R.P.); (E.C.); (C.P.); (M.C.); (M.P.); (G.R.); (M.S.); (A.T.)
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90127 Palermo, Italy
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Jang HN, Moon SJ, Jung JH, Han KD, Rhee EJ, Lee WY. Impact of Diabetes on COVID-19 Susceptibility: A Nationwide Propensity Score Matching Study. Endocrinol Metab (Seoul) 2024; 39:813-818. [PMID: 39192772 PMCID: PMC11525691 DOI: 10.3803/enm.2024.2014] [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: 04/17/2024] [Revised: 06/03/2024] [Accepted: 06/13/2024] [Indexed: 08/29/2024] Open
Abstract
Prior research has highlighted poor clinical outcomes in coronavirus disease 2019 (COVID-19)-infected patients with diabetes; however, susceptibility to COVID-19 infection in patients with diabetes has not been extensively studied. Participants aged ≥30 years who underwent COVID-19 testing from December 2019 to April 2020 were analyzed using the National Health Insurance Service data in South Korea. In a cohort comprising 29,433 1:1 propensity score-matched participants, COVID-19 positivity was significantly higher in participants with diabetes than in those without diabetes (512 [3.5%] vs. 395 [2.7%], P<0.001). Logistic regression analysis indicated that diabetes significantly increased the risk of COVID-19 test positivity (odds ratio, 1.307; 95% confidence interval, 1.144 to 1.493; P<0.001). Patients with diabetes exhibited heightened COVID-19 infection rates compared to individuals without diabetes, and diabetes increased the susceptibility to COVID-19, reinforcing the need for heightened preventive measures, particularly considering the poor clinical outcomes in this group.
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Affiliation(s)
- Han Na Jang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sun Joon Moon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
- Department of Internal Medicine, Sungkyunkwan University School of Medicine, Suwon, Korea
| | - Jin Hyung Jung
- Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kyung-Do Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Korea
| | - Eun-Jung Rhee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
- Department of Internal Medicine, Sungkyunkwan University School of Medicine, Suwon, Korea
| | - Won-Young Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
- Department of Internal Medicine, Sungkyunkwan University School of Medicine, Suwon, Korea
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Lee H, Kim MJ, Lee IK, Hong CW, Jeon JH. Impact of hyperglycemia on immune cell function: a comprehensive review. Diabetol Int 2024; 15:745-760. [PMID: 39469566 PMCID: PMC11512986 DOI: 10.1007/s13340-024-00741-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 06/10/2024] [Indexed: 10/30/2024]
Abstract
Hyperglycemia, a hallmark of diabetes and various metabolic disorders, has profound implications for immune cell function. The relationship between elevated blood glucose levels and immune cell function is a topic of significant medical interest. In this review, we aim to comprehensively review effects of hyperglycemia on various immune cell types and its clinical implications, particularly T cells, macrophages, natural killer cells, and neutrophils. It aims to consolidate current knowledge on the subject, with a focus on both type 1 and type 2 diabetes, as well as other pathological states where hyperglycemia is a concern. A comprehensive examination of recent studies and clinical data was conducted to assess effects of hyperglycemia on immune cell function. Evidence indicates that hyperglycemia can significantly alter immune cell function, with different diabetic conditions showing varied responses. Roles of key metabolic hormones in regulating T cell function highlight potential therapeutic targets for restoring immune balance. In addition, reprogramming of innate immune cells such as macrophages and natural killer cells under hyperglycemic conditions suggests a complex metabolic-immunological interface. This review will contribute to a better understanding of the link between diabetes, other metabolic disorders, and immune function. By examining recent research and clinical findings, this review will enhance our comprehension of the mechanisms at play and guide future medical strategies for managing and treating conditions associated with hyperglycemia.
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Affiliation(s)
- Hoyul Lee
- Research Institute of Aging and Metabolism, Kyungpook National University, Daegu, Republic of Korea
| | - Min-Ji Kim
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, 807 Hoguk-Ro, Buk-Gu, Daegu, 41404 Republic of Korea
| | - In-Kyu Lee
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Chang-Won Hong
- Department of Physiology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Jae-Han Jeon
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, 807 Hoguk-Ro, Buk-Gu, Daegu, 41404 Republic of Korea
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12
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Park CY, Shin S, Han SN. Multifaceted Roles of Vitamin D for Diabetes: From Immunomodulatory Functions to Metabolic Regulations. Nutrients 2024; 16:3185. [PMID: 39339785 PMCID: PMC11435169 DOI: 10.3390/nu16183185] [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: 08/30/2024] [Revised: 09/15/2024] [Accepted: 09/19/2024] [Indexed: 09/30/2024] Open
Abstract
Numerous studies have established associations between vitamin D and diabetes. The vitamin D receptor is widely distributed throughout the human body, including in pancreatic beta cells (β-cells), hepatocytes, and immune cells. Therefore, vitamin D's effect on the risk, progression, or complications of diabetes may be mediated through various mechanisms. These include the regulation of insulin secretion or sensitivity and modulation of β-cell function and its immunomodulatory and anti-inflammatory effects. This review extensively explores the relationship between vitamin D status and diabetes, as well as the preventive or therapeutic effects of vitamin D supplementation on diabetes from human studies. Additionally, it examines in detail the impact of vitamin D on immune and inflammatory responses in the diabetic milieux and β-cell function to better understand the underlying mechanisms through which vitamin D influences diabetes.
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Affiliation(s)
- Chan Yoon Park
- Department of Food & Nutrition, College of Life Care Science Technology, The University of Suwon, Hwaseong-si 18323, Republic of Korea
| | - Sunhye Shin
- Department of Food and Nutrition, College of Science and Convergence Technology, Seoul Women's University, Seoul 01797, Republic of Korea
| | - Sung Nim Han
- Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul 08826, Republic of Korea
- Research Institute of Human Ecology, Seoul National University, Seoul 08826, Republic of Korea
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Sudirman S, Hwang YY, Su CH, Lu TY, Kuo HP, Hwang DF, Kong ZL. Blue mussel ( Mytilus edulis) water extract ameliorates intestinal immune response in high-fat diet-streptozotocin-induced diabetic mice. Food Funct 2024; 15:9357-9367. [PMID: 39189105 DOI: 10.1039/d3fo04639g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/28/2024]
Abstract
Diabetes mellitus is a metabolic disease characterized by high blood glucose levels or hyperglycemia. Diabetes causes a decrease in immune function in the human body. Mytilus edulis has been identified as having anti-inflammatory properties and the ability to improve inflammation. Thus, this study aimed to investigate the function of Matsu M. edulis water extract (MWE) in mediating the regulation of immune responses and dysregulating the intestinal immune system in hyperglycemia mouse models. The mice were treated with MWE for seven weeks. The results showed that treatment with MWE has the ability to decrease triglyceride and total cholesterol concentrations. MWE also increases the interleukin (IL)-10 concentration and natural killer cell activation. It also improves the phagocytic capacity of monocytes in the colon and the proliferative capacity of lymphocytes in the mesentery. Furthermore, MWE also regulates the IL-6 concentration and the ratio of T helper 17 cells to regulatory T cells. Collectively, this extract can improve dyslipidemia, inflammatory responses, and dysregulation of the intestinal immune system. Therefore, M. edulis water extract can be used as an alternative treatment to reduce diabetes complications.
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Affiliation(s)
- Sabri Sudirman
- Fisheries Product Technology, Faculty of Agriculture, Universitas Sriwijaya, Indralaya 30862, Indonesia
| | - Yi-Yuh Hwang
- Department of Food Science, National Taiwan Ocean University, Keelung City 20224, Taiwan.
| | - Chia-Hung Su
- Department of Food Science, National Taiwan Ocean University, Keelung City 20224, Taiwan.
| | - Ting-Yu Lu
- National Formosa University, Yunlin County, Taiwan
| | - Hsiang-Ping Kuo
- Department of Food Science, National Taiwan Ocean University, Keelung City 20224, Taiwan.
| | - Deng-Fwu Hwang
- Department of Food Science, National Taiwan Ocean University, Keelung City 20224, Taiwan.
| | - Zwe-Ling Kong
- Department of Food Science, National Taiwan Ocean University, Keelung City 20224, Taiwan.
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14
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Huang X, Mao W, Hu X, Qin F, Zhao H, Zhang A, Wang X, Stoppe C, Zhou D, Ke L, Ni H, Chinese Acute Pancreatitis Clinical Trials Group (CAPCTG). Immune-Enhancing Treatment among Acute Necrotizing Pancreatitis Patients with Metabolic Abnormalities: A Post Hoc Analysis of a Randomized Clinical Trial. Gut Liver 2024; 18:906-914. [PMID: 38356344 PMCID: PMC11391137 DOI: 10.5009/gnl230326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 10/08/2023] [Accepted: 11/01/2023] [Indexed: 02/16/2024] Open
Abstract
Background/Aims Metabolic syndrome is common in patients with acute pancreatitis and its components have been reported to be associated with infectious complications. In this post hoc analysis, we aimed to evaluate whether metabolic abnormalities impact the effect of immune-enhancing thymosin alpha-1 (Tα1) therapy in acute necrotizing pancreatitis (ANP) patients. Methods All data were obtained from the database for a multicenter randomized clinical trial that evaluated the efficacy of Tα1 in ANP patients. Patients who discontinued the Tα1 treatment prematurely were excluded. The primary outcome was 90-day infected pancreatic necrosis (IPN) after randomization. Three post hoc subgroups were defined based on the presence of hyperglycemia, hypertriglyceridemia, or both at the time of randomization. In each subgroup, the correlation between Tα1 and 90-day IPN was assessed using the Cox proportional-hazards regression model. Multivariable propensity-score methods were used to control potential bias. Results Overall, 502 participants were included in this post hoc analysis (248 received Tα1 treatment and 254 received matching placebo treatment). Among them, 271 (54.0%) had hyperglycemia, 371 (73.9%) had hypertriglyceridemia and 229 (45.6%) had both. Tα1 therapy was associated with reduced incidence of IPN among patients with hyperglycemia (18.8% vs 29.7%: hazard ratio, 0.80; 95% confidence interval, 0.37 to 0.97; p=0.03), but not in the other subgroups. Additional multivariate regression models using three propensity-score methods yielded similar results. Conclusions Among ANP patients with hyperglycemia, immune-enhancing Tα1 treatment was associated with a reduced risk of IPN (ClinicalTrials.gov, Registry number: NCT02473406).
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Affiliation(s)
- Xiaofei Huang
- Department of Emergency and Critical Care Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
- Department of Emergency and Critical Care Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
| | - Wenjian Mao
- Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Xingxing Hu
- Department of Emergency and Critical Care Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
- Department of Emergency and Critical Care Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
| | - Fengxia Qin
- Department of Emergency and Critical Care Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
- Department of Emergency and Critical Care Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
- Department of Emergency and Critical Care Medicine, Nanjing Jiangning District Hospital of Traditional Chinese Medicine, Nanjing, China
| | - Hui Zhao
- Department of Emergency and Critical Care Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
- Department of Emergency and Critical Care Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
| | - Aiping Zhang
- Department of Emergency and Critical Care Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
- Department of Emergency and Critical Care Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
| | - Xinyu Wang
- Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Christian Stoppe
- Department of Anesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Würzburg, Würzburg, Germany
- Department of Cardiac Anesthesiology and Intensive Care Medicine, German Heart Center Charité Berlin, Berlin, Germany
| | - Dandan Zhou
- Department of Emergency and Critical Care Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
- Department of Emergency and Critical Care Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
| | - Lu Ke
- Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
- National Institute of Healthcare Data Science, Nanjing University, Nanjing, China
| | - Haibin Ni
- Department of Emergency and Critical Care Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
- Department of Emergency and Critical Care Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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15
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K S, J O, N M, I T, A F, AR E. Perioperative Blood Glucose Optimization in Orthopaedic Trauma Patients. OPERATIVE TECHNIQUES IN ORTHOPAEDICS 2024; 34:101128. [DOI: 10.1016/j.oto.2024.101128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Hou XJ, Qin MY, Liu YQ, Zhao Q, Wang FJ, Bai L. Effects of motivational interviewing intervention on psychological status, compliance behavior and quality of life of patients with malignant tumor combined with diabetes mellitus. Pak J Med Sci 2024; 40:1087-1092. [PMID: 38952500 PMCID: PMC11190389 DOI: 10.12669/pjms.40.6.7627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 09/05/2023] [Accepted: 02/15/2024] [Indexed: 07/03/2024] Open
Abstract
Objective To investigate the effects of motivational interview education on psychological status, compliance behavior and quality of life in patients with malignant tumors combined with diabetes mellitus. Methods This is a retrospective study. Eighty patients with malignant tumors combined with diabetes mellitus admitted at The Fourth Hospital of Hebei Medical University from January 2021 to June 2022 were included as subjects and divided into observation group and control group according to the intervention measures. Patients in the control group were given routine health education intervention, while those in the observation group were given motivational interviewing intervention on the basis of the control group. We compared the prognosis, cognitive function, quality of life, relief of cancer pain before intervention and three months after the intervention of the two groups were compared. Results At three months after the intervention, the total remission rate of cancer pain in the observation group was higher than that in the control group(p<0.05), while the levels of FBG and 2hPG in the observation group were significantly lower than those in the control group(p<0.05). Self-Rating Anxiety Scale(SAS) and Self-rating depression scale(SDS) scores decreased in both groups three months after the intervention, with the level of reduction in the observation group being higher than that in the control group(p<0.05). The overall compliance was higher in the observation group than in the control group(p<0.05). Conclusion Motivational interviewing leads to alleviate negative emotions, improve the psychological status, enhance compliance behavior and improve quality of life in patients with malignant tumors combined with diabetes mellitus.
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Affiliation(s)
- Xiao-juan Hou
- Xiao-juan Hou, Department of Endocrinology, The Fourth Hospital of Hebei Medical University, Shijiangzhuang 050011, Hebei, P.R. China
| | - Ming-yi Qin
- Ming-yi Qin, Department of Nursing, The Fourth Hospital of Hebei Medical University, Shijiangzhuang 050011, Hebei, P.R. China
| | - Yue-qin Liu
- Yue-qin Liu, Department of Endocrinology, The Fourth Hospital of Hebei Medical University, Shijiangzhuang 050011, Hebei, P.R. China
| | - Qin Zhao
- Qin Zhao, Department of Endocrinology, The Fourth Hospital of Hebei Medical University, Shijiangzhuang 050011, Hebei, P.R. China
| | - Fu-jun Wang
- Fu-jun Wang, Department of Endocrinology, The Fourth Hospital of Hebei Medical University, Shijiangzhuang 050011, Hebei, P.R. China
| | - Lei Bai
- Lei Bai, Department of Endocrinology, The Fourth Hospital of Hebei Medical University, Shijiangzhuang 050011, Hebei, P.R. China
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17
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Oh M, Jung S, Kim YA, Lee GY, Han SN. Dietary vitamin D 3 supplementation enhances splenic NK cell activity in healthy and diabetic male mice. Nutr Res 2024; 127:144-155. [PMID: 38954977 DOI: 10.1016/j.nutres.2024.06.004] [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: 01/13/2024] [Revised: 06/03/2024] [Accepted: 06/04/2024] [Indexed: 07/04/2024]
Abstract
Type 2 diabetes mellitus negatively affects the immune system, resulting in reduced natural killer (NK) cell activity. Vitamin D has been shown to regulate innate and adaptive immune cells. However, the effects of vitamin D on NK cells remain inconclusive, especially in the context of diabetes. We hypothesized that dietary vitamin D3 supplementation can enhance NK cell activity in diabetic mice. Therefore, we investigated the effects of dietary vitamin D3 on NK cell activity in control and diabetic mice and explored the mechanisms of NK cell activity modulation by vitamin D3. Control (CON) and diabetic mice (db/db) were randomly divided into 2 groups, then fed either a control diet (948 IU vitamin D3/kg diet, vDC) or a diet supplemented with vitamin D3 (9,477 IU vitamin D3/kg diet, vDS) for 8 weeks. Diabetic mice exhibited lower NK cell activity than control mice. The vDS group had significantly higher NK cell activity than the vDC group in both control and diabetic mice. The vDS group had a higher percentage of CD11b single-positive NK cells than the vDC group (CON-vDS 34%; db/db-vDS 30%; CON-vDC 27%; db/db-vDC 22%). The intracellular expression of splenic TGF-β was significantly higher in the db/db group than in the CON group. Overall, vDS group had higher Bcl2 and Tbx21 mRNA expressions than the vDC group. In conclusion, the present study shows that NK cell activity is impaired under diabetic conditions, possibly due to the reduced percentage of mature NK cells. Moreover, NK activity is enhanced by dietary supplementation in both control and diabetic mice that may be associated with changes in the proportion of mature NK cells.
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Affiliation(s)
- Minha Oh
- Department of Food and Nutrition, Seoul National University, Seoul, Republic of Korea
| | - Sohee Jung
- Department of Food and Nutrition, Seoul National University, Seoul, Republic of Korea
| | - Yoon-Ah Kim
- Department of Food and Nutrition, Seoul National University, Seoul, Republic of Korea
| | - Ga Young Lee
- Department of Food and Nutrition, Seoul National University, Seoul, Republic of Korea
| | - Sung Nim Han
- Department of Food and Nutrition, Seoul National University, Seoul, Republic of Korea; Research Institute of Human Ecology, Seoul National University, Seoul, Republic of Korea.
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von Hofsten J, Zetterberg M. Risk Factors for Cytomegalovirus Retinitis in a National Survey in Sweden. Ocul Immunol Inflamm 2024; 32:485-492. [PMID: 36625562 DOI: 10.1080/09273948.2022.2154679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 10/23/2022] [Accepted: 11/28/2022] [Indexed: 01/11/2023]
Abstract
PURPOSE To investigate predisposing immunosuppressive conditions causing cytomegalovirus retinitis (CMVr) and risk factors for delayed diagnosis in patients diagnosed between 2008 and 2018 in the Swedish population of 10 million. RESULTS Sixty-three consecutive patients (100 eyes) were diagnosed with CMVr. The most common immunosuppressive state predisposing for CMVr was hematopoietic stem cell transplant recipients (27%) and hematological malignancy (24%). Two patients (3.2%) had no other predisposing factor than diabetes mellitus (DM). Patients with delayed diagnosis (≤30 days) were older than those with earlier diagnosis, mean age 68.7 (±9.8) and 48.8 (±17.6), respectively, p = .001. Signs of intraocular inflammation (IOI) were seen in 42 (70%) of cases and more common in delayed than early diagnosis, 16 (89%) and 21 (60%) respectively (p = .03). CONCLUSION Delayed diagnosis was more common in older individuals with signs of IOI. DM may be a risk factor for CMVr, and clinical signs can be mistaken for diabetic retinopathy.
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Affiliation(s)
- Joanna von Hofsten
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
- Department of Ophthalmology, Halland Hospital Halmstad, Halmstad, Sweden
| | - Madeleine Zetterberg
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
- Department of Ophthalmology, Sahlgrenska University Hospital, Mölndal, Sweden
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Alexander M, Cho E, Gliozheni E, Salem Y, Cheung J, Ichii H. Pathology of Diabetes-Induced Immune Dysfunction. Int J Mol Sci 2024; 25:7105. [PMID: 39000211 PMCID: PMC11241249 DOI: 10.3390/ijms25137105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 06/18/2024] [Accepted: 06/19/2024] [Indexed: 07/16/2024] Open
Abstract
Diabetes is associated with numerous comorbidities, one of which is increased vulnerability to infections. This review will focus on how diabetes mellitus (DM) affects the immune system and its various components, leading to the impaired proliferation of immune cells and the induction of senescence. We will explore how the pathology of diabetes-induced immune dysfunction may have similarities to the pathways of "inflammaging", a persistent low-grade inflammation common in the elderly. Inflammaging may increase the likelihood of conditions such as rheumatoid arthritis (RA) and periodontitis at a younger age. Diabetes affects bone marrow composition and cellular senescence, and in combination with advanced age also affects lymphopoiesis by increasing myeloid differentiation and reducing lymphoid differentiation. Consequently, this leads to a reduced immune system response in both the innate and adaptive phases, resulting in higher infection rates, reduced vaccine response, and increased immune cells' senescence in diabetics. We will also explore how some diabetes drugs induce immune senescence despite their benefits on glycemic control.
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Affiliation(s)
- Michael Alexander
- Division of Transplantation, Department of Surgery, University of California, Irvine, CA 92868, USA
| | - Eric Cho
- Division of Transplantation, Department of Surgery, University of California, Irvine, CA 92868, USA
| | - Eiger Gliozheni
- Division of Transplantation, Department of Surgery, University of California, Irvine, CA 92868, USA
| | - Yusuf Salem
- Division of Transplantation, Department of Surgery, University of California, Irvine, CA 92868, USA
| | - Joshua Cheung
- Division of Transplantation, Department of Surgery, University of California, Irvine, CA 92868, USA
| | - Hirohito Ichii
- Division of Transplantation, Department of Surgery, University of California, Irvine, CA 92868, USA
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20
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Trandafir MF, Savu OI, Gheorghiu M. The Complex Immunological Alterations in Patients with Type 2 Diabetes Mellitus on Hemodialysis. J Clin Med 2024; 13:3687. [PMID: 38999253 PMCID: PMC11242658 DOI: 10.3390/jcm13133687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Revised: 06/14/2024] [Accepted: 06/23/2024] [Indexed: 07/14/2024] Open
Abstract
It is widely known that diabetes mellitus negatively impacts both the innate immunity (the inflammatory response) and the acquired immunity (the humoral and cellular immune responses). Many patients with diabetes go on to develop chronic kidney disease, which will necessitate hemodialysis. In turn, long-term chronic hemodialysis generates an additional chronic inflammatory response and impairs acquired immunity. The purpose of this paper is to outline and compare the mechanisms that are the basis of the constant aggression towards self-components that affects patients with diabetes on hemodialysis, in order to find possible new therapeutic ways to improve the functionality of the immune system. Our study will take a detailed look at the mechanisms of endothelial alteration in diabetes and hemodialysis, at the mechanisms of inflammatory generation and signaling at different levels and also at the mechanisms of inflammation-induced insulin resistance. It will also discuss the alterations in leukocyte chemotaxis, antigen recognition and the dysfunctionalities in neutrophils and macrophages. Regarding acquired immunity, we will outline the behavioral alterations of T and B lymphocytes induced by diabetes mellitus and chronic hemodialysis.
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Affiliation(s)
- Maria-Florina Trandafir
- Pathophysiology and Immunology Department, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania;
- Doctoral School, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania;
| | - Octavian Ionel Savu
- Doctoral School, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania;
- “N. C. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, 020475 Bucharest, Romania
| | - Mihaela Gheorghiu
- Pathophysiology and Immunology Department, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania;
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Cosmin Stan M, Paul D. Diabetes and Cancer: A Twisted Bond. Oncol Rev 2024; 18:1354549. [PMID: 38835644 PMCID: PMC11148650 DOI: 10.3389/or.2024.1354549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 04/08/2024] [Indexed: 06/06/2024] Open
Abstract
This paper presents an overview of the interconnection between various factors related to both cancer and type 2 diabetes mellitus (T2DM). Hyperglycemia, hyperinsulinemia, chronic inflammation, and obesity are involved in the development and progression of both diseases but, strong evidence for a direct causal relationship between diabetes and cancer, is lacking. Several studies described a relationship between hyperglycemia and cancer at the cellular, tissular and organismic levels but at the same time recent Mendelian randomization studies proved a significant causal relationship only between hyperglycemia and breast cancer. On the other hand, the association between both hyperinsulinemia and obesity and several cancer types appears to be robust as demonstrated by Mendelian randomized studies. Metabolic alterations, including the Warburg effect and excessive glucose consumption by tumors, are discussed, highlighting the potential impact of dietary restrictions, such as fasting and low-carb diets, on tumor growth and inflammation. Recent data indicates that circulating branched-chain amino acids levels, may represent novel biomarkers that may contribute to both better diabetes control and early pancreatic cancer detection. Understanding the underlying mechanisms and shared risk factors between cancer and T2DM can provide valuable insights for cancer prevention, early detection, and management strategies.
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Affiliation(s)
- Mihai Cosmin Stan
- Emergency County Hospital Rm. Vâlcea, Râmnicu Vâlcea, Romania
- Medical Oncology Department, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | - Doru Paul
- Weill Cornell Medicine, New York, NY, United States
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Xu D, Yuan L, Che M, Liu W, Li X, Yang Y, Wang K, Nan Y. The molecular mechanism of "Dahuang-Shengjiang-Banxia decoction" in the treatment of diabetic kidney disease was verified based on network pharmacology and molecular docking. Heliyon 2024; 10:e24776. [PMID: 38312712 PMCID: PMC10835317 DOI: 10.1016/j.heliyon.2024.e24776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 01/04/2024] [Accepted: 01/14/2024] [Indexed: 02/06/2024] Open
Abstract
Background Explore the molecular mechanism of Dahuang-Shengjiang-Banxia Decoction (DSBD) in the treatment of diabetic kidney disease (DKD), using network pharmacology and molecular docking technology. Method The effective ingredients and targets of the DSBD were taken from the TCMSP database, while the disease targets were obtained via GeneCards, OMIM, DrugBank, TTD, and DisGeNET. Cytoscape 3.9.1 was used to create a drug-ingredient-target network diagram. STRING databases are also used to analyze the Protein-Protein Interaction (PPI) network of intersecting targets. The core targets was obtained by the intersection of the differential genes screened from the intersection target and GEO, and the core targets was enriched by Gene ontology (GO), Kyoto gene and genome (KEGG), and Gene Set Enrichment Analysis (GSEA). CIBERSORTx was used for immunoinfiltration analysis, and then the core targets was analyzed by Nephroseq V5 and KIT for clinical correlation analysis and single-cell sequencing. Lastly, AutoDock Vina was used for molecular docking of both the core targets and the top active elements. Results A total of 177 DSBD and 2906 DKD targets were screened. Six core targets were identified by screening, which were IL1B, MMP9, EGF, VEGFA, HIF1A, and PTGS2. The top 6 active ingredients are 6-gingerol, baicalin, oleic acid, β-sitosterol, linolenic acid, and aloe emodin. The core targets has good docking activity with the active ingredient. Conclusion DSBD may exert its therapeutic effect on DKD through multicomponent, multipath, and multi-target analyses. It is possible that VEGFA is a key target in therapy, and that the VEGF/PI3K/AKT signaling pathway plays a key role in therapy.
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Affiliation(s)
- Duojie Xu
- Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan, 750004, Ningxia, China
| | - Ling Yuan
- College of Pharmacy, Ningxia Medical University, Yinchuan, 750004, Ningxia, China
| | - Mengying Che
- Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan, 750004, Ningxia, China
| | - Wenjing Liu
- Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan, 750004, Ningxia, China
| | - Xiangyang Li
- Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan, 750004, Ningxia, China
| | - Yifan Yang
- Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan, 750004, Ningxia, China
| | - Kaili Wang
- Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan, 750004, Ningxia, China
| | - Yi Nan
- Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan, 750004, Ningxia, China
- Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan, 750004, Ningxia, China
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23
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Zhao L, Fan K, Sun X, Li W, Qin F, Shi L, Gao F, Zheng C. Host-directed therapy against mycobacterium tuberculosis infections with diabetes mellitus. Front Immunol 2024; 14:1305325. [PMID: 38259491 PMCID: PMC10800548 DOI: 10.3389/fimmu.2023.1305325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Accepted: 12/11/2023] [Indexed: 01/24/2024] Open
Abstract
Tuberculosis (TB) is caused by the bacterial pathogen Mycobacterium tuberculosis (MTB) and is one of the principal reasons for mortality and morbidity worldwide. Currently, recommended anti-tuberculosis drugs include isoniazid, rifampicin, ethambutol, and pyrazinamide. TB treatment is lengthy and inflicted with severe side-effects, including reduced patient compliance with treatment and promotion of drug-resistant strains. TB is also prone to other concomitant diseases such as diabetes and HIV. These drug-resistant and complex co-morbid characteristics increase the complexity of treating MTB. Host-directed therapy (HDT), which effectively eliminates MTB and minimizes inflammatory tissue damage, primarily by targeting the immune system, is currently an attractive complementary approach. The drugs used for HDT are repositioned drugs in actual clinical practice with relative safety and efficacy assurance. HDT is a potentially effective therapeutic intervention for the treatment of MTB and diabetic MTB, and can compensate for the shortcomings of current TB therapies, including the reduction of drug resistance and modulation of immune response. Here, we summarize the state-of-the-art roles and mechanisms of HDT in immune modulation and treatment of MTB, with a special focus on the role of HDT in diabetic MTB, to emphasize the potential of HDT in controlling MTB infection.
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Affiliation(s)
- Li Zhao
- Department of Tuberculosis III, Wuhan Pulmonary Hospital, Wuhan, Hubei, China
| | - Ke Fan
- Department of Tuberculosis III, Wuhan Pulmonary Hospital, Wuhan, Hubei, China
| | - Xuezhi Sun
- Department of Tuberculosis III, Wuhan Pulmonary Hospital, Wuhan, Hubei, China
| | - Wei Li
- Department of Tuberculosis III, Wuhan Pulmonary Hospital, Wuhan, Hubei, China
| | - Fenfen Qin
- Department of Tuberculosis III, Wuhan Pulmonary Hospital, Wuhan, Hubei, China
| | - Liwen Shi
- Department of Tuberculosis III, Wuhan Pulmonary Hospital, Wuhan, Hubei, China
| | - Feng Gao
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Chunlan Zheng
- Department of Tuberculosis III, Wuhan Pulmonary Hospital, Wuhan, Hubei, China
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24
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Konadu E, Essuman MA, Amponsah A, Agroh WXK, Badu-Boateng E, Gbedema SY, Boakye YD. Enteric Protozoan Parasitosis and Associated Factors among Patients with and without Diabetes Mellitus in a Teaching Hospital in Ghana. Int J Microbiol 2023; 2023:5569262. [PMID: 38105772 PMCID: PMC10725318 DOI: 10.1155/2023/5569262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 11/21/2023] [Accepted: 11/27/2023] [Indexed: 12/19/2023] Open
Abstract
Background Enteric protozoa infections (EPIs) could worsen clinical outcomes in patients with diabetes mellitus and therefore requires prompt and accurate diagnosis and attention. This study aimed to determine the burden of EPIs and their associated factors among patients with and without diabetics at the Komfo Anokye Teaching Hospital (KATH) in Ghana. Again, the diagnostic performance of parasitological techniques routinely used for diagnosis was assessed. Methods A total of 240 participants (made up of 140 patients with diabetes and 100 patients without diabetes) were recruited into the study by simple random sampling from November 2020 to May 2021. Stool samples of participants were collected, along with their demographic information, and examined using the saline direct wet mount (DWM), formol-ether concentration (FEC), and modified Ziehl-Neelsen staining (ZNS) techniques for the presence of enteric protozoans. Results Enteric protozoa were found among 62/140 (44.3%) diabetic patients and 13/100 (13.0%) nondiabetic patients. The predominant protozoa identified were Cryptosporidium spp. (17.86%) among patients with diabetes and Blastocystis hominis (7.0%) among patients without diabetes. EPI was associated with diabetes mellitus status (AOR = 3.48, 95% CI, 1.55-7.79), having diabetes for more than five years (AOR = 3.83, 95% CI, 1.65-8.86) and having comorbidity (AOR = 2.93, 95% CI, 1.33-6.45). The FEC technique had the highest sensitivity (100.0%), specificity 94.3% (95% CI, 91.35-97.22), and accuracy 95.0% (95% CI, 88.54-98.13) when compared to other techniques for diagnosis. Conclusion EPIs are a significant health problem among patients with diabetes at KATH, and therefore antiparasitic drugs should be included in their treatment protocols for better health outcomes. Again, the FEC technique has demonstrated better performance in detecting EPIs and is therefore recommended to achieve early and accurate diagnosis of EPIs.
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Affiliation(s)
- Eric Konadu
- Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
- Department of Microbiology, Parasitology Laboratory Unit, Komfo Anokye Teaching Hospital, Kumasi, Ghana
| | - Mainprice Akuoko Essuman
- Department of Medical Laboratory Science, School of Allied Health Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana
- Department of Biological Sciences, Southern Illinois University Edwardsville, Edwardsville, Illinois, USA
| | - Angela Amponsah
- Department of Medical Laboratory Science, School of Allied Health Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Wisdom Xoese Kwadzo Agroh
- Department of Medical Laboratory Science, School of Allied Health Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Ernest Badu-Boateng
- Department of Microbiology, Parasitology Laboratory Unit, Komfo Anokye Teaching Hospital, Kumasi, Ghana
| | - Stephen Yao Gbedema
- Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Yaw Duah Boakye
- Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
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El Safadi D, Paulo-Ramos A, Hoareau M, Roche M, Krejbich-Trotot P, Viranaicken W, Lebeau G. The Influence of Metabolism on Immune Response: A Journey to Understand Immunometabolism in the Context of Viral Infection. Viruses 2023; 15:2399. [PMID: 38140640 PMCID: PMC10748259 DOI: 10.3390/v15122399] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Revised: 12/04/2023] [Accepted: 12/07/2023] [Indexed: 12/24/2023] Open
Abstract
In recent years, the emergence of the concept of immunometabolism has shed light on the pivotal role that cellular metabolism plays in both the activation of immune cells and the development of immune programs. The antiviral response, a widely distributed defense mechanism used by infected cells, serves to not only control infections but also to attenuate their deleterious effects. The exploration of the role of metabolism in orchestrating the antiviral response represents a burgeoning area of research, especially considering the escalating incidence of viral outbreaks coupled with the increasing prevalence of metabolic diseases. Here, we present a review of current knowledge regarding immunometabolism and the antiviral response during viral infections. Initially, we delve into the concept of immunometabolism by examining its application in the field of cancer-a domain that has long spearheaded inquiries into this fascinating intersection of disciplines. Subsequently, we explore examples of immune cells whose activation is intricately regulated by metabolic processes. Progressing with a systematic and cellular approach, our aim is to unravel the potential role of metabolism in antiviral defense, placing significant emphasis on the innate and canonical interferon response.
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Affiliation(s)
- Daed El Safadi
- PIMIT—Processus Infectieux en Milieu Insulaire Tropical, Université de La Réunion, INSERM UMR 1187, CNRS 9192, IRD 249, Plateforme CYROI, 97490 Sainte-Clotilde, France; (D.E.S.); (M.R.); (P.K.-T.)
| | - Aurélie Paulo-Ramos
- INSERM, UMR 1188 Diabète Athérothrombose Réunion Océan Indien (DéTROI), Université de La Réunion, Campus Santé de Terre Sainte, 97410 Saint-Pierre, France; (A.P.-R.)
| | - Mathilde Hoareau
- INSERM, UMR 1188 Diabète Athérothrombose Réunion Océan Indien (DéTROI), Université de La Réunion, Campus Santé de Terre Sainte, 97410 Saint-Pierre, France; (A.P.-R.)
| | - Marjolaine Roche
- PIMIT—Processus Infectieux en Milieu Insulaire Tropical, Université de La Réunion, INSERM UMR 1187, CNRS 9192, IRD 249, Plateforme CYROI, 97490 Sainte-Clotilde, France; (D.E.S.); (M.R.); (P.K.-T.)
| | - Pascale Krejbich-Trotot
- PIMIT—Processus Infectieux en Milieu Insulaire Tropical, Université de La Réunion, INSERM UMR 1187, CNRS 9192, IRD 249, Plateforme CYROI, 97490 Sainte-Clotilde, France; (D.E.S.); (M.R.); (P.K.-T.)
| | - Wildriss Viranaicken
- PIMIT—Processus Infectieux en Milieu Insulaire Tropical, Université de La Réunion, INSERM UMR 1187, CNRS 9192, IRD 249, Plateforme CYROI, 97490 Sainte-Clotilde, France; (D.E.S.); (M.R.); (P.K.-T.)
- INSERM, UMR 1188 Diabète Athérothrombose Réunion Océan Indien (DéTROI), Université de La Réunion, Campus Santé de Terre Sainte, 97410 Saint-Pierre, France; (A.P.-R.)
| | - Grégorie Lebeau
- PIMIT—Processus Infectieux en Milieu Insulaire Tropical, Université de La Réunion, INSERM UMR 1187, CNRS 9192, IRD 249, Plateforme CYROI, 97490 Sainte-Clotilde, France; (D.E.S.); (M.R.); (P.K.-T.)
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26
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Yu L, Guo S, Ji W, Sun H, Lee S, Zhang D. Intervention Effects of Physical Activity on Type 2 Diabetic Patients Potentially Infected with COVID-19. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1772. [PMID: 37893490 PMCID: PMC10608032 DOI: 10.3390/medicina59101772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/10/2023] [Revised: 10/01/2023] [Accepted: 10/03/2023] [Indexed: 10/29/2023]
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has clearly had a great influence on the lifestyles of the population, especially on patients with type 2 diabetes mellitus. During the COVID-19 outbreak, many countries/regions implemented social-isolation measures, leading to an increase in negative behaviors and impairing the capability of diabetic patients to resist COVID-19, ultimately causing severe prognoses. Moreover, as the epidemic progressed, multiple studies emphasized the significance of physical exercise in the management of type 2 diabetic patients infected with COVID-19. In this study, we selected research from 1 December 2019 to 9 August 2023 that focused on COVID-19-infected diabetic patients to investigate the impact of type 2 diabetes on the immune functions, inflammation factor levels, lung injuries, and mental disorders of such patients, as well as to assess the risk of novel coronavirus pneumonia in these patients. Additionally, the effects of high-intensity, moderate-intensity, and low-intensity exercises on novel coronavirus pneumonia infection in type 2 diabetic patients and the mechanisms of the effects of such exercise were considered. We concluded that elderly diabetic patients with COVID-19 should perform low-intensity exercises to facilitate their recoveries. This study offers guidance for a proper understanding of the dangers of diabetes and the use of appropriate measures to reduce the risk of novel coronavirus pneumonia infections in type 2 diabetic patients.
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Affiliation(s)
- Lihua Yu
- College of Arts and Sports, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; (L.Y.)
- Institute of Public Foundations, University of Health and Rehabilitation Sciences, Qingdao 266000, China
| | - Sainyu Guo
- College of Arts and Sports, Myongji University, Seoul 04763, Republic of Korea
| | - Wen Ji
- College of Arts and Sports, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; (L.Y.)
| | - Hailian Sun
- College of Arts and Sports, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; (L.Y.)
| | - Seongno Lee
- College of Arts and Sports, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; (L.Y.)
| | - Deju Zhang
- Food and Nutritional Sciences, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, 0000, Hong Kong
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27
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De Barra C, O'Shea D, Hogan AE. NK cells vs. obesity: A tale of dysfunction & redemption. Clin Immunol 2023; 255:109744. [PMID: 37604354 DOI: 10.1016/j.clim.2023.109744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Revised: 08/08/2023] [Accepted: 08/15/2023] [Indexed: 08/23/2023]
Abstract
Natural killer (NK) cells are critical in protecting the body against infection and cancer. NK cells can rapidly respond to these threats by directly targeting the infected or transformed cell using their cytotoxic machinery or by initiating and amplifying the immune response via their production of cytokines. Additionally, NK cells are resident across many tissues including adipose, were their role extends from host protection to tissue homeostasis. Adipose resident NK cells can control macrophage polarization via cytokine production, whilst also regulating stressed adipocyte fate using their cytotoxic machinery. Obesity is strongly associated with increased rates of cancer and a heightened susceptibility to severe infections. This is in part due to significant obesity-related immune dysregulation, including defects in both peripheral and adipose tissue NK cells. In this review, we detail the literature to date on NK cells in the setting of obesity - outlining the consequences, mechanisms and therapeutic interventions.
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Affiliation(s)
- Conor De Barra
- Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co Kildare, Ireland
| | - Donal O'Shea
- Obesity Immunology Group, Education and Research Centre, St Vincent's University Hospital, University College, Dublin 4, Ireland
| | - Andrew E Hogan
- Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co Kildare, Ireland; National Children's Research Centre, Dublin 12, Ireland.
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28
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Luan Y, Luan Y, He H, Jue B, Yang Y, Qin B, Ren K. Glucose metabolism disorder: a potential accomplice of SARS-CoV-2. Int J Obes (Lond) 2023; 47:893-902. [PMID: 37542197 DOI: 10.1038/s41366-023-01352-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 06/29/2023] [Accepted: 07/14/2023] [Indexed: 08/06/2023]
Abstract
Globally, 265,713,467 confirmed cases of SARS-CoV-2 (CoV-2), including 5,260,888 deaths, have been reported by the WHO. It is important to study the mechanism of this infectious disease. A variety of evidences show the potential association between CoV-2 and glucose metabolism. Notably, people with type 2 diabetes mellitus (T2DM) and other metabolic complications were prone to have a higher risk of developing a more severe infection course than people who were metabolically normal. The correlations between glucose metabolism and CoV-2 progression have been widely revealed. This review will discuss the association between glucose metabolism disorders and CoV-2 progression, showing the promoting effect of diabetes and other diseases related to glucose metabolism disorders on the progression of CoV-2. We will further conclude the effects of key proteins and pathways in glucose metabolism regulation on CoV-2 progression and potential interventions by targeting glucose metabolism disorders for CoV-2 treatment. Therefore, this review will provide systematic insight into the treatment of CoV-2 from the perspective of glucose metabolism.
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Affiliation(s)
- Yi Luan
- Department of Translational Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Ying Luan
- State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing, 100000, China
| | - Hongbo He
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450001, China
| | - Bolin Jue
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453000, China
| | - Yang Yang
- Department of Translational Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
| | - Bo Qin
- Department of Translational Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
| | - Kaidi Ren
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
- Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, 450052, China.
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29
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Navasardyan I, Yeganyan S, Nguyen H, Vaghashia P, Subbian S, Venketaraman V. Role of Oxidative Stress in Tuberculosis Meningitis Infection in Diabetics. Biomedicines 2023; 11:2568. [PMID: 37761009 PMCID: PMC10526095 DOI: 10.3390/biomedicines11092568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Revised: 09/10/2023] [Accepted: 09/14/2023] [Indexed: 09/29/2023] Open
Abstract
Tuberculosis meningitis (TBM) is a result of the invasion of the meninges with the bacilli of Mycobacterium tuberculosis (Mtb), leading to inflammation of the meninges around the brain or spinal cord. Oxidative stress occurs when the body's cells become overwhelmed with free radicals, particularly reactive oxygen species (ROS). ROS plays a significant role in the pathogenesis of TBM due to their toxic nature, resulting in impairment of the body's ability to fight off infection. ROS damages the endothelial cells and impairs the defense mechanisms of the blood-brain barrier (BBB), which contributes to CNS susceptibility to the bacteria causing TBM. Diabetes mellitus (DM) is a common condition that is characterized by the impairment of the hormone insulin, which is responsible for modulating blood glucose levels. The increased availability of glucose in individuals with diabetes results in increased cellular activity and metabolism, leading to heightened ROS production and, in turn, increased susceptibility to TBM. In this review, we summarize our current understanding of oxidative stress and its role in both TBM and DM. We further discuss how increased oxidative stress in DM can contribute to the likelihood of developing TBM and potential therapeutic approaches that may be of therapeutic value.
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Affiliation(s)
- Inesa Navasardyan
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA; (I.N.); (S.Y.); (H.N.); (P.V.)
| | - Stephanie Yeganyan
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA; (I.N.); (S.Y.); (H.N.); (P.V.)
| | - Helena Nguyen
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA; (I.N.); (S.Y.); (H.N.); (P.V.)
| | - Payal Vaghashia
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA; (I.N.); (S.Y.); (H.N.); (P.V.)
| | - Selvakumar Subbian
- Public Health Research Center, New Jersey Medical School, Rutgers University, Newark, NJ 07103, USA;
| | - Vishwanath Venketaraman
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA; (I.N.); (S.Y.); (H.N.); (P.V.)
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30
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Cortellini A, D'Alessio A, Cleary S, Buti S, Bersanelli M, Bordi P, Tonini G, Vincenzi B, Tucci M, Russo A, Pantano F, Russano M, Stucci LS, Sergi MC, Falconi M, Zarzana MA, Santini D, Spagnolo F, Tanda ET, Rastelli F, Giorgi FC, Pergolesi F, Giusti R, Filetti M, Lo Bianco F, Marchetti P, Botticelli A, Gelibter A, Siringo M, Ferrari M, Marconcini R, Vitale MG, Nicolardi L, Chiari R, Ghidini M, Nigro O, Grossi F, De Tursi M, Di Marino P, Queirolo P, Bracarda S, Macrini S, Inno A, Zoratto F, Veltri E, Spoto C, Vitale MG, Cannita K, Gennari A, Morganstein DL, Mallardo D, Nibid L, Sabarese G, Brunetti L, Perrone G, Ascierto PA, Ficorella C, Pinato DJ. Type 2 Diabetes Mellitus and Efficacy Outcomes from Immune Checkpoint Blockade in Patients with Cancer. Clin Cancer Res 2023; 29:2714-2724. [PMID: 37125965 DOI: 10.1158/1078-0432.ccr-22-3116] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 02/14/2023] [Accepted: 04/25/2023] [Indexed: 05/02/2023]
Abstract
PURPOSE No evidence exists as to whether type 2 diabetes mellitus (T2DM) impairs clinical outcome from immune checkpoint inhibitors (ICI) in patients with solid tumors. EXPERIMENTAL DESIGN In a large cohort of ICI recipients treated at 21 institutions from June 2014 to June 2020, we studied whether patients on glucose-lowering medications (GLM) for T2DM had shorter overall survival (OS) and progression-free survival (PFS). We used targeted transcriptomics in a subset of patients to explore differences in the tumor microenvironment (TME) of patients with or without diabetes. RESULTS A total of 1,395 patients were included. Primary tumors included non-small cell lung cancer (NSCLC; 54.7%), melanoma (24.7%), renal cell (15.0%), and other carcinomas (5.6%). After multivariable analysis, patients on GLM (n = 226, 16.2%) displayed an increased risk of death [HR, 1.29; 95% confidence interval (CI),1.07-1.56] and disease progression/death (HR, 1.21; 95% CI, 1.03-1.43) independent of number of GLM received. We matched 92 metformin-exposed patients with 363 controls and 78 patients on other oral GLM or insulin with 299 control patients. Exposure to metformin, but not other GLM, was associated with an increased risk of death (HR, 1.53; 95% CI, 1.16-2.03) and disease progression/death (HR, 1.34; 95% CI, 1.04-1.72). Patients with T2DM with higher pretreatment glycemia had higher neutrophil-to-lymphocyte ratio (P = 0.04), while exploratory tumoral transcriptomic profiling in a subset of patients (n = 22) revealed differential regulation of innate and adaptive immune pathways in patients with T2DM. CONCLUSIONS In this study, patients on GLM experienced worse outcomes from immunotherapy, independent of baseline features. Prospective studies are warranted to clarify the relative impact of metformin over a preexisting diagnosis of T2DM in influencing poorer outcomes in this population.
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Affiliation(s)
- Alessio Cortellini
- Operative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom
| | - Antonio D'Alessio
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom
- Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
| | - Siobhan Cleary
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom
| | - Sebastiano Buti
- Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | | | - Paola Bordi
- Medical Oncology Unit, University Hospital of Parma, Parma, Italy
| | - Giuseppe Tonini
- Operative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy
| | - Bruno Vincenzi
- Operative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy
| | - Marco Tucci
- Department of Interdisciplinary Medicine (DIM), University of Bari "Aldo Moro", Italy
- Medical Oncology Unit, Policlinico Hospital of Bari, Bari, Italy
| | - Alessandro Russo
- Medical Oncology, A.O. Papardo & Department of Human Pathology, University of Messina, Messina, Italy
| | - Francesco Pantano
- Operative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy
| | - Marco Russano
- Operative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy
| | | | | | - Martina Falconi
- Medical Oncology, A.O. Papardo & Department of Human Pathology, University of Messina, Messina, Italy
| | - Maria Antonietta Zarzana
- Medical Oncology, A.O. Papardo & Department of Human Pathology, University of Messina, Messina, Italy
| | - Daniele Santini
- UOC Oncologia Medica territoriale, La Sapienza University, Polo Pontino, Rome, Italy
| | | | - Enrica T Tanda
- IRCCS Ospedale Policlinico San Martino, Genova, Italy
- Genetics of Rare Cancers, Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy
| | - Francesca Rastelli
- UOC Oncologia Ascoli Piceno - San Benedetto del Tronto, Ascoli Piceno, Italy
| | | | - Federica Pergolesi
- UOC Oncologia Ascoli Piceno - San Benedetto del Tronto, Ascoli Piceno, Italy
| | - Raffaele Giusti
- Azienda Ospedaliera Sant'Andrea, Sapienza University of Rome, Rome, Italy
| | - Marco Filetti
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
- Early Phase Trials, Policlinico Agostino Gemelli IRCCS, Rome, Italy
| | | | - Paolo Marchetti
- Istituto Dermopatico dell'Immacolata: IDI IRCCS, Rome, Italy
| | - Andrea Botticelli
- Department of Clinical and Molecular Oncology, "Sapienza" University of Rome, Rome, Italy
| | - Alain Gelibter
- Department of Clinical and Molecular Oncology, "Sapienza" University of Rome, Rome, Italy
| | - Marco Siringo
- Department of Clinical and Molecular Oncology, "Sapienza" University of Rome, Rome, Italy
| | - Marco Ferrari
- Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | | | | | | | - Rita Chiari
- UOC Oncologia, Azienda Ospedaliera Marche Nord, Pesaro, Italy
| | - Michele Ghidini
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Olga Nigro
- Medical Oncology, ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi, Varese, Italy
| | - Francesco Grossi
- Medical Oncology, ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi, Varese, Italy
- Division of Medical Oncology, University of Insubria, Varese, Italy
| | - Michele De Tursi
- Department of Innovative Technologies in Medicine & Dentistry, University G. D'Annunzio, Chieti-Pescara, Italy
| | | | - Paola Queirolo
- Division of Medical Oncology for Melanoma, Sarcoma, and Rare Tumors, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Sergio Bracarda
- S.C. Medical Oncology, Azienda Ospedaliera S. Maria, Terni, Italy
| | - Serena Macrini
- S.C. Medical Oncology, Azienda Ospedaliera S. Maria, Terni, Italy
| | - Alessandro Inno
- Oncology Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Verona, Italy
| | | | - Enzo Veltri
- Medical Oncology, Santa Maria Goretti Hospital, Latina, Italy
| | - Chiara Spoto
- Medical Oncology, Santa Maria Goretti Hospital, Latina, Italy
| | - Maria Grazia Vitale
- Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori-IRCCS Fondazione "G. Pascale", Naples, Italy
| | - Katia Cannita
- Medical Oncology Unit, Department of Oncology, Teramo, Italy
| | - Alessandra Gennari
- Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
| | - Daniel L Morganstein
- Skin Unit, Royal Marsden Hospital, London, United Kingdom
- Department of Endocrinology, Chelsea and Westminster Hospital, London, United Kingdom
| | - Domenico Mallardo
- Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori-IRCCS Fondazione "G. Pascale", Naples, Italy
| | - Lorenzo Nibid
- Pathology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy
| | - Giovanna Sabarese
- Pathology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy
| | - Leonardo Brunetti
- Operative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy
| | - Giuseppe Perrone
- Pathology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy
| | - Paolo A Ascierto
- Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori-IRCCS Fondazione "G. Pascale", Naples, Italy
| | - Corrado Ficorella
- Department of Biotechnology and Applied Clinical Science, University of L'Aquila, L'Aquila, Italy
| | - David J Pinato
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom
- Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
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31
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Liu Y, Zhang C, Song M, Han X, Jiao D. Predicting early biliary infection after stenting of malignant biliary obstruction: model development and internal validation. Abdom Radiol (NY) 2023; 48:2456-2465. [PMID: 37160766 DOI: 10.1007/s00261-023-03936-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Revised: 04/19/2023] [Accepted: 04/20/2023] [Indexed: 05/11/2023]
Abstract
PURPOSE To analyze the risk factors and develop a clinical prediction model for early biliary infection (EBI) after percutaneous transhepatic biliary stenting (PTBS) in patients with malignant biliary obstruction (MBO). METHODS The clinical data of 236 patients with MBO treated with PTBS from June 2012 to June 2021 were retrospectively analyzed. Independent risk factors were analyzed by univariate and multivariate logistic regression, and a nomogram model was constructed based on the results. Discrimination, calibration, and clinical usefulness of this model were further assessed. RESULTS The technical success rate of PTBS was 100%, and EBI after PTBS was 20.3%. Multivariate logistic regression analysis showed that hilar MBO (P = 0.020), diabetes (P = 0.001), previous surgical or endoscopic intervention (P = 0.007), procedure time > 60 min (P = 0.007), and intraprocedural biliary hemorrhage (P = 0.003) were independent risk factors for EBI after PTBS. A nomogram model was developed to predict the probability of EBI. ROC curves showed good discrimination of the model (area under curve = 0.831). The calibration plot indicated that the predicted probability of EBI by this model was in good agreement with the actual probability of EBI. The DCA curves showed that the net benefit of nomogram-assisted decisions was higher than or equal to the net benefit of treatment for all or none at a wide threshold probability (0-0.8). CONCLUSION The nomogram model based on the above independent risk factors can predict the probability of EBI and model-assisted treatment decisions contribute to improved clinical outcome. Therefore, MBO patients with probability of EBI > 0.20 based on the model should be recommended for perioperative broad-spectrum antibiotics and close monitoring.
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Affiliation(s)
- Yiming Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou, 450052, China
| | - Chengzhi Zhang
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou, 450052, China
| | - Mengyao Song
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou, 450052, China
| | - Xinwei Han
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou, 450052, China
| | - Dechao Jiao
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou, 450052, China.
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32
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Borovcanin MM, Vesic K, Petrovic I, Jovanovic IP, Mijailović NR. Diabetes mellitus type 2 as an underlying, comorbid or consequent state of mental disorders. World J Diabetes 2023; 14:481-493. [PMID: 37273248 PMCID: PMC10236997 DOI: 10.4239/wjd.v14.i5.481] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 03/21/2023] [Accepted: 04/12/2023] [Indexed: 05/15/2023] Open
Abstract
Somatic disturbances that occur in parallel with psychiatric diseases are a major challenge in clinical practice. Various factors contribute to the development of mental and somatic disorders. Type 2 diabetes mellitus (T2DM) is a significant health burden worldwide, and the prevalence of diabetes in adults is increasing. The comorbidity of diabetes and mental disorders is very common. By sharing a bidirectional link, both T2DM and mental disorders influence each other in various manners, but the exact mechanisms underlying this link are not yet elucidated. The potential mechanisms of both mental disorders and T2DM are related to immune and inflammatory system dysfunction, oxidative stress, endothelial dysfunction, and metabolic disturbances. Moreover, diabetes is also a risk factor for cognitive dysfunction that can range from subtle diabetes-associated cognitive decline to pre-dementia and dementia. A complex re-lationship between the gut and the brain also represents a new therapeutic approach since gut-brain signalling pathways regulate food intake and hepatic glucose production. The aim of this minireview is to summarize and present the latest data on mutual pathogenic pathways in these disorders, emphasizing their complexity and interweaving. We also focused on the cognitive performances and changes in neurodegenerative disorders. The importance of implementing integrated approaches in treating both of these states is highlighted, along with the need for individual therapeutic strategies.
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Affiliation(s)
- Milica M Borovcanin
- Department of Psychiatry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34 000, Serbia
| | - Katarina Vesic
- Department of Neurology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34 000, Serbia
| | - Ivica Petrovic
- Department of Pathophysiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34 000, Serbia
| | - Ivan P Jovanovic
- Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34 000, Serbia
| | - Nataša R Mijailović
- Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34 000, Serbia
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33
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Management of Invasive Infections in Diabetes Mellitus: A Comprehensive Review. BIOLOGICS 2023. [DOI: 10.3390/biologics3010004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/08/2023]
Abstract
Patients with diabetes often have more invasive infections, which may lead to an increase in morbidity. The hyperglycaemic environment promotes immune dysfunction (such as the deterioration of neutrophil activity, antioxidant system suppression, and compromised innate immunity), micro- and microangiopathies, and neuropathy. A greater number of medical interventions leads to a higher frequency of infections in diabetic patients. Diabetic individuals are susceptible to certain conditions, such as rhino-cerebral mucormycosis or aspergillosis infection. Infections may either be the primary symptom of diabetes mellitus or act as triggers in the intrinsic effects of the disease, such as diabetic ketoacidosis and hypoglycaemia, in addition to increasing morbidity. A thorough diagnosis of the severity and origin of the infection is necessary for effective treatment, which often entails surgery and extensive antibiotic use. Examining the significant issue of infection in individuals with diabetes is crucial. Comprehensive research should examine why infections are more common amongst diabetics and what the preventive treatment strategies could be.
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34
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Mailliez A, Ternynck C, Duhamel A, Mailliez A, Ploquin A, Desauw C, Lemaitre M, Bertrand N, Vambergue A, Turpin A. Diabetes is associated with high risk of severe adverse events during chemotherapy for cancer patients: A single-center study. Int J Cancer 2023; 152:408-416. [PMID: 36054752 PMCID: PMC10087807 DOI: 10.1002/ijc.34268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 05/31/2022] [Accepted: 06/02/2022] [Indexed: 02/01/2023]
Abstract
Diabetes mellitus (DM) is a common comorbidity among cancer patients, but its impact on chemotherapy tolerance has not been widely studied. We aimed to compare the occurrence of severe grade 3/4 adverse events (G3/4 AEs) within 90 days of starting chemotherapy between patients with and without diabetes. We conducted a retrospective single-center study in Lille University Hospital Oncology Department, France. Patients who received the first cycle of chemotherapy for gastrointestinal, gynecological or cancer of unknown primary source between 1 May 2013 and 1 May 2016, were included. Overall, 609 patients were enrolled: 490 patients without diabetes (80.5%) and 119 patients with diabetes (19.5%). Within 90 days of starting chemotherapy, patients with diabetes had a significantly higher occurrence of AEs G3/4 compared to those with no diabetes (multivariate odds ratio [OR]: 1.57 [1.02-2.42], P = .04). More frequent G3/4 AEs in patients with diabetes were infection (26%), hematological disorders (13%), endocrine disorders (13%) and deterioration of the general condition (13%). In the year following the beginning of chemotherapy, patients with diabetes were twice as likely to be hospitalized as those without diabetes (univariate OR: 2.1 [1.40-3.15], P = .0003). After multivariate adjustment, diabetes was no longer significantly associated with the risk of hospitalization (P = .051). There were no differences between patients with and without diabetes regarding dose reduction and chemotherapy treatment delays (P = .61 and P = .30, respectively). Our study suggests the need for better consideration of DM in the personalized care plan to improve chemotherapy tolerance and quality of life of patients with DM.
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Affiliation(s)
- Aurélie Mailliez
- Department of Geriatrics, CHU Lille, Lille, France.,U1167-RID-AGE-Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, Université de Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France
| | - Camille Ternynck
- ULR 2694-METRICS: Évaluation Des Technologies De Santé Et Des Pratiques Médicales, Université de Lille, CHU Lille, Lille, France
| | - Alain Duhamel
- ULR 2694-METRICS: Évaluation Des Technologies De Santé Et Des Pratiques Médicales, Université de Lille, CHU Lille, Lille, France
| | - Audrey Mailliez
- Medical Oncology Department, Breast Cancer Unit, Oscar Lambret Center, Lille, France
| | - Anne Ploquin
- Medical Oncology Department, CHU Lille, ULR 2694 METRICS, University of Lille, Lille, France
| | - Christophe Desauw
- Medical Oncology Department, CHU Lille, ULR 2694 METRICS, University of Lille, Lille, France
| | - Madleen Lemaitre
- CHU Lille, Department of Diabetology, Endocrinology, Metabolism and Nutrition, Lille University Hospital, Lille, France.,European Genomic Institute for Diabetes, Lille University School of Medicine, Lille, France
| | - Nicolas Bertrand
- Medical Oncology Department, CHU Lille, ULR 2694 METRICS, University of Lille, Lille, France
| | - Anne Vambergue
- CHU Lille, Department of Diabetology, Endocrinology, Metabolism and Nutrition, Lille University Hospital, Lille, France.,European Genomic Institute for Diabetes, Lille University School of Medicine, Lille, France
| | - Anthony Turpin
- CHU Lille, Institut Pasteur de Lille, UMR9020-UMR-S 1277-Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, University of Lille, CNRS, Inserm, Lille, France.,Medical Oncology Department, CHU Lille, University of Lille, Lille, France
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35
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Shin U, You H, Lee GY, Son Y, Han SN. The effects of 1,25(OH) 2D 3 treatment on metabolic reprogramming and maturation in bone marrow-derived dendritic cells from control and diabetic mice. J Steroid Biochem Mol Biol 2023; 225:106197. [PMID: 36183994 DOI: 10.1016/j.jsbmb.2022.106197] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 08/17/2022] [Accepted: 09/26/2022] [Indexed: 02/01/2023]
Abstract
Activated dendritic cells (DCs) undergo significant metabolic reprogramming, which is characterized by an increase in aerobic glycolysis and a concurrent progressive loss of oxidative phosphorylation. The modulation of metabolic reprogramming is believed to be closely related to the function of DCs. Vitamin D has been reported to inhibit the maturation of DCs. DC dysfunction has been reported in diabetic patients, and hyperglycemia is associated with impaired glycolytic metabolism in immune cells. Therefore, vitamin D and diabetes may affect intracellular metabolism, thereby regulating the activity of DCs. We investigated the effect of in vitro treatment of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on metabolic reprogramming and maturation of bone marrow-derived dendritic cells (BMDCs) from diabetic mouse. Six-week-old male C57BLKS/J-m+/m+ mice (CON) and C57BLKS/J-db/db mice (db/db) were fed with a 10% kcal fat diet for seven weeks. BMDCs were generated by culturing bone marrow cells from the mice with rmGM-CSF (20 ng/mL) in the absence or presence of 10 nM 1,25(OH)2D3. The maturation of BMDCs was induced via lipopolysaccharide (LPS, 50 ng/mL) stimulation for 24 h. LPS stimulation induced iNOS protein expression and decreased the mitochondrial respiration, while increased lactate production and the expression of glycolytic pathway-related genes (Glut1 and Pfkfb3) in BMDCs from both CON and db/db groups. In LPS-stimulated mature BMDCs, 1,25(OH)2D3 treatment decreased the expression of surface markers related to immunostimulatory functions (MHC class II, CD80, CD86, and CD40) and production of IL-12p70 in both CON and db/db groups. While the mRNA level of the gene related to glucose uptake (Glut1) was increased in both groups, lactate production was decreased by 1,25(OH)2D3 treatment. mTORC1 activity was suppressed following 1,25(OH)2D3 treatment. Collectively, our findings confirmed that metabolic reprogramming occurred in BMDCs following LPS stimulation. In vitro 1,25(OH)2D3 treatment induced tolerogenic phenotypes by reducing the expression of surface markers, as well as cytokine production. However, no significant difference was observed regarding the effects of 1,25(OH)2D3 treatment on metabolic conversion and maturation of BMDCs between the control and diabetic mice. Additionally, the decreased aerobic glycolysis induced by the 1,25(OH)2D3 treatment appeared to be associated with the diminished maturation of BMDCs, and mTORC1 appears to play a key role in the 1,25(OH)2D3-mediated regulation of glycolysis.
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Affiliation(s)
- Ungue Shin
- Department of Food and Nutrition, Seoul National University, Seoul, the Republic of Korea.
| | - Hyeyoung You
- Department of Food and Nutrition, Seoul National University, Seoul, the Republic of Korea.
| | - Ga Young Lee
- Department of Food and Nutrition, Seoul National University, Seoul, the Republic of Korea.
| | - YeKyoung Son
- Department of Food and Nutrition, Seoul National University, Seoul, the Republic of Korea.
| | - Sung Nim Han
- Department of Food and Nutrition, Seoul National University, Seoul, the Republic of Korea; Research Institute of Human Ecology, Seoul National University, Seoul, the Republic of Korea.
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36
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Dey S, Murmu N, Mondal T, Saha I, Chatterjee S, Manna R, Haldar S, Dash SK, Sarkar TR, Giri B. Multifaceted entrancing role of glucose and its analogue, 2-deoxy-D-glucose in cancer cell proliferation, inflammation, and virus infection. Biomed Pharmacother 2022; 156:113801. [DOI: 10.1016/j.biopha.2022.113801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 09/29/2022] [Accepted: 10/02/2022] [Indexed: 11/30/2022] Open
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37
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Al Ansari Y, Shahwan H, Chrcanovic BR. Diabetes Mellitus and Dental Implants: A Systematic Review and Meta-Analysis. MATERIALS (BASEL, SWITZERLAND) 2022; 15:3227. [PMID: 35591561 PMCID: PMC9105616 DOI: 10.3390/ma15093227] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 04/15/2022] [Accepted: 04/28/2022] [Indexed: 01/08/2023]
Abstract
The present review aimed to evaluate the impact of diabetes mellitus on dental implant failure rates and marginal bone loss (MBL). An electronic search was undertaken in three databases, plus a manual search of journals. Meta-analyses were performed as well as meta-regressions in order to verify how the odds ratio (OR) and MBL were associated with follow-up time. The review included 89 publications. Altogether, there were 5510 and 62,780 implants placed in diabetic and non-diabetic patients, respectively. Pairwise meta-analysis showed that implants in diabetic patients had a higher failure risk in comparison to non-diabetic patients (OR 1.777, p < 0.001). Implant failures were more likely to occur in type 1 diabetes patients than in type 2 (OR 4.477, p = 0.032). The difference in implant failure between the groups was statistically significant in the maxilla but not in the mandible. The MBL mean difference (MD) between the groups was 0.776 mm (p = 0.027), with an estimated increase of 0.032 mm in the MBL MD between groups for every additional month of follow-up (p < 0.001). There was an estimated decrease of 0.007 in OR for every additional month of follow-up (p = 0.048). In conclusion, implants in diabetic patients showed a 77.7% higher risk of failure than in non-diabetic patients.
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Affiliation(s)
- Yasmin Al Ansari
- Faculty of Odontology, Malmö University, 214 21 Malmo, Sweden; (Y.A.A.); (H.S.)
| | - Halime Shahwan
- Faculty of Odontology, Malmö University, 214 21 Malmo, Sweden; (Y.A.A.); (H.S.)
| | - Bruno Ramos Chrcanovic
- Department of Prosthodontics, Faculty of Odontology, Malmö University, 214 21 Malmo, Sweden
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38
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Wang H, Cao K, Liu S, Xu Y, Tang L. Tim-3 Expression Causes NK Cell Dysfunction in Type 2 Diabetes Patients. Front Immunol 2022; 13:852436. [PMID: 35464400 PMCID: PMC9018664 DOI: 10.3389/fimmu.2022.852436] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 03/16/2022] [Indexed: 11/17/2022] Open
Abstract
Type 2 diabetes mellitus (T2DM) is characterized by high blood glucose levels and chronic low-grade inflammation. It shows a strong association with obesity and immune dysfunction, which makes T2DM patients more susceptible to infectious diseases. NK cells play an important role in pathogen control and tumor surveillance. However, whether NK cell distribution and functional status are altered in T2DM is unclear. To address this issue, we compared surface receptor expression and cytokine production between peripheral blood NK cells from 90 T2DM patients and 62 age- and sex-matched healthy controls. We found a significantly lower frequency and absolute number of NK cells in patients than in controls. Interestingly, the expression of inhibitory receptor Tim-3 was significantly increased, while the expression of the activating receptor NKG2D was significantly decreased, in T2DM NK cells. Both TNF-α secretion and degranulation capacity (evidenced by CD107a expression) were dampened in NK cells from patients. The expression of Tim-3 on NK cells correlated positively with both HbA1c and fasting blood glucose levels and negatively with the percentage and absolute number of total NK cells and was associated with increased NK cell apoptosis. In addition, Tim-3 expression on NK cells negatively correlated with TNF-α production, which could be restored by blocking Galectin-9/Tim-3 pathway. Our results suggest that NK cell dysfunction secondary to augmented Tim-3 expression occurs in T2DM patients, which may partly explain their increased susceptibility to cancer and infectious disease.
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Affiliation(s)
- Hui Wang
- Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Kangli Cao
- Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Siyu Liu
- Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yuanhong Xu
- Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Ling Tang
- Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, China
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39
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Pasman R, Krom BP, Zaat SAJ, Brul S. The Role of the Oral Immune System in Oropharyngeal Candidiasis-Facilitated Invasion and Dissemination of Staphylococcus aureus. FRONTIERS IN ORAL HEALTH 2022; 3:851786. [PMID: 35464779 PMCID: PMC9021398 DOI: 10.3389/froh.2022.851786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 02/25/2022] [Indexed: 11/13/2022] Open
Abstract
Candida albicans and Staphylococcus aureus account for most invasive fungal and bacterial bloodstream infections (BSIs), respectively. However, the initial point of invasion responsible for S. aureus BSIs is often unclear. Recently, C. albicans has been proposed to mediate S. aureus invasion of immunocompromised hosts during co-colonization of oral mucosal surfaces. The status of the oral immune system crucially contributes to this process in two distinct ways: firstly, by allowing invasive C. albicans growth during dysfunction of extra-epithelial immunity, and secondly following invasion by some remaining function of intra-epithelial immunity. Immunocompromised individuals at risk of developing invasive oral C. albicans infections could, therefore, also be at risk of contracting concordant S. aureus BSIs. Considering the crucial contribution of both oral immune function and dysfunction, the aim of this review is to provide an overview of relevant aspects of intra and extra-epithelial oral immunity and discuss predominant immune deficiencies expected to facilitate C. albicans induced S. aureus BSIs.
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Affiliation(s)
- Raymond Pasman
- Department of Molecular Biology and Microbial Food Safety, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, Netherlands
| | - Bastiaan P. Krom
- Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, Netherlands
| | - Sebastian A. J. Zaat
- Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam, Netherlands
| | - Stanley Brul
- Department of Molecular Biology and Microbial Food Safety, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, Netherlands
- *Correspondence: Stanley Brul
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40
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Zanetti M, Xian S, Dosset M, Carter H. The Unfolded Protein Response at the Tumor-Immune Interface. Front Immunol 2022; 13:823157. [PMID: 35237269 PMCID: PMC8882736 DOI: 10.3389/fimmu.2022.823157] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Accepted: 01/26/2022] [Indexed: 12/14/2022] Open
Abstract
The tumor-immune interface has surged to primary relevance in an effort to understand the hurdles facing immune surveillance and cancer immunotherapy. Reports over the past decades have indicated a role for the unfolded protein response (UPR) in modulating not only tumor cell fitness and drug resistance, but also local immunity, with emphasis on the phenotype and altered function of immune cells such as myeloid cells and T cells. Emerging evidence also suggests that aneuploidy correlates with local immune dysregulation. Recently, we reported that the UPR serves as a link between aneuploidy and immune cell dysregulation in a cell nonautonomous way. These new findings add considerable complexity to the organization of the tumor microenvironment (TME) and the origin of its altered function. In this review, we summarize these data and also discuss the role of aneuploidy as a negative regulator of local immunity.
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Affiliation(s)
- Maurizio Zanetti
- The Laboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California San Diego, La Jolla, CA, United States
- *Correspondence: Maurizio Zanetti, ; orcid.org/0000-0001-6346-8776
| | - Su Xian
- Division of Medical Genetics, Department of Medicine, Bioinformatics and System Biology Program, University of California San Diego, La Jolla, CA, United States
| | - Magalie Dosset
- The Laboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California San Diego, La Jolla, CA, United States
| | - Hannah Carter
- Division of Medical Genetics, Department of Medicine, Bioinformatics and System Biology Program, University of California San Diego, La Jolla, CA, United States
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Keilen J, Gar C, Rottenkolber M, Fueessl L, Joseph AT, Draenert R, Seissler J, Lechner A. No association of natural killer cell number and function in peripheral blood with overweight/obesity and metabolic syndrome in a cohort of young women. Physiol Rep 2022; 10:e15148. [PMID: 35179822 PMCID: PMC8855889 DOI: 10.14814/phy2.15148] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 11/28/2021] [Accepted: 11/30/2021] [Indexed: 06/14/2023] Open
Abstract
AIM To reexamine the associations of NK cell number and function in the peripheral blood with overweight/obesity and the metabolic syndrome in a large, well-phenotyped human cohort. METHODS Cross-sectional analysis of 273 women in the PPSDiab Study; measurement of absolute and relative number of NK cells in peripheral blood, and of functional parameters CD69 positivity and cytotoxicity against K562 cells; group comparison of NK cell characteristics between lean, overweight, and obese participants, as well as metabolic syndrome scores of 0, 1, 2, and ≥3; Spearman correlation analyses to clinical parameters related to the metabolic syndrome. RESULTS We found no differences in NK cell number and function between lean, overweight, and obese women (relative NK cell number (median (Q1-Q3), [%]) 5.1(2.6-9.4) vs. 4.8 (2.9-8.4) vs. 3.8 (1.7-7.8), p = 0.187; absolute NK cell number [106 /L]: 86.9 (44.6-188.8) vs. 92.6 (52.5-154.6) vs. 85.9 (44-153.8), p = 0.632; CD69+ [%]: 27.2 (12.9-44.3) vs. 37.6 (13.2-52.8) vs. 33.6 (16.3-45), p = 0.136; cytotoxicity [%]: 11.0 (7.1-14.5) vs. 8.5 (6.4-13.2) vs. 11.3 (8.7-14.2), p = 0.094), as well as between different metabolic syndrome scores. Nonesterified fatty acids correlated with absolute and relative NK cell number and cytotoxicity (ρ [p-value]: 0.142 [0.021], 0.119 [0.049], and 0.131 [0.035], respectively). Relative NK cell number further correlated with high-density lipoprotein cholesterol (0.144 [0.018]) and cytotoxicity with 2 h glucose in oral glucose tolerance testing (0.132 [0.034]). CD69 positivity correlated with body fat (0.141 [0.021]), triglycerides (0.129 [0.033]), and plasma leptin (0.155 [0.010]). After correction for multiple testing, none of the associations remained significant. CONCLUSION In the present study, we observed no associations of NK cell number and function in the peripheral blood with overweight/obesity and the metabolic syndrome. Extreme phenotypes of obesity and the metabolic syndrome might have caused differing results in previous studies. Further analyses with a focus on compartments other than peripheral blood may help to clarify the relation between NK cells and metabolic diseases.
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Affiliation(s)
- Julia Keilen
- Diabetes Research GroupDepartment of Medicine IVUniversity HospitalLMU MunichMunichGermany
- Clinical Cooperation Group DiabetesLudwig‐Maximilians‐Universität München and Helmholtz Zentrum MünchenMunichGermany
- German Center for Diabetes Research (DZD)München‐NeuherbergGermany
| | - Christina Gar
- Diabetes Research GroupDepartment of Medicine IVUniversity HospitalLMU MunichMunichGermany
- Clinical Cooperation Group DiabetesLudwig‐Maximilians‐Universität München and Helmholtz Zentrum MünchenMunichGermany
- German Center for Diabetes Research (DZD)München‐NeuherbergGermany
| | - Marietta Rottenkolber
- Diabetes Research GroupDepartment of Medicine IVUniversity HospitalLMU MunichMunichGermany
- Clinical Cooperation Group DiabetesLudwig‐Maximilians‐Universität München and Helmholtz Zentrum MünchenMunichGermany
- German Center for Diabetes Research (DZD)München‐NeuherbergGermany
| | - Louise U. Fueessl
- Diabetes Research GroupDepartment of Medicine IVUniversity HospitalLMU MunichMunichGermany
- Clinical Cooperation Group DiabetesLudwig‐Maximilians‐Universität München and Helmholtz Zentrum MünchenMunichGermany
- German Center for Diabetes Research (DZD)München‐NeuherbergGermany
| | - Anna T. Joseph
- Diabetes Research GroupDepartment of Medicine IVUniversity HospitalLMU MunichMunichGermany
- Clinical Cooperation Group DiabetesLudwig‐Maximilians‐Universität München and Helmholtz Zentrum MünchenMunichGermany
- German Center for Diabetes Research (DZD)München‐NeuherbergGermany
| | - Rika Draenert
- Stabsstelle Antibiotic StewardshipLMU Klinikum MunichMunichGermany
| | - Jochen Seissler
- Diabetes Research GroupDepartment of Medicine IVUniversity HospitalLMU MunichMunichGermany
- Clinical Cooperation Group DiabetesLudwig‐Maximilians‐Universität München and Helmholtz Zentrum MünchenMunichGermany
- German Center for Diabetes Research (DZD)München‐NeuherbergGermany
| | - Andreas Lechner
- Diabetes Research GroupDepartment of Medicine IVUniversity HospitalLMU MunichMunichGermany
- Clinical Cooperation Group DiabetesLudwig‐Maximilians‐Universität München and Helmholtz Zentrum MünchenMunichGermany
- German Center for Diabetes Research (DZD)München‐NeuherbergGermany
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Palano MT, Cucchiara M, Gallazzi M, Riccio F, Mortara L, Gensini GF, Spinetti G, Ambrosio G, Bruno A. When a Friend Becomes Your Enemy: Natural Killer Cells in Atherosclerosis and Atherosclerosis-Associated Risk Factors. Front Immunol 2022; 12:798155. [PMID: 35095876 PMCID: PMC8793801 DOI: 10.3389/fimmu.2021.798155] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 12/14/2021] [Indexed: 12/15/2022] Open
Abstract
Atherosclerosis (ATS), the change in structure and function of arteries with associated lesion formation and altered blood flow, is the leading cause of cardiovascular disease, the number one killer worldwide. Beyond dyslipidemia, chronic inflammation, together with aberrant phenotype and function of cells of both the innate and adaptive immune system, are now recognized as relevant contributors to atherosclerosis onset and progression. While the role of macrophages and T cells in atherosclerosis has been addressed in several studies, Natural Killer cells (NKs) represent a poorly explored immune cell type, that deserves attention, due to NKs’ emerging contribution to vascular homeostasis. Furthermore, the possibility to re-polarize the immune system has emerged as a relevant tool to design new therapies, with some succesfull exmples in the field of cancer immunotherapy. Thus, a deeper knowledge of NK cell pathophysiology in the context of atherosclerosis and atherosclerosis-associated risk factors could help developing new preventive and treatment strategies, and decipher the complex scenario/history from “the risk factors for atherosclerosis” Here, we review the current knowledge about NK cell phenotype and activities in atherosclerosis and selected atherosclerosis risk factors, namely type-2 diabetes and obesity, and discuss the related NK-cell oriented environmental signals.
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Affiliation(s)
- Maria Teresa Palano
- Laboratory of Innate Immunity, Unit of Molecular Pathology, Biochemistry and Immunology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica, Milano, Italy
| | - Martina Cucchiara
- Laboratory of Immunology and General Pathology, Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy
| | - Matteo Gallazzi
- Laboratory of Immunology and General Pathology, Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy
| | - Federica Riccio
- Laboratory of Cardiovascular Physiopathology-Regenerative Medicine, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica, Milano, Italy
| | - Lorenzo Mortara
- Laboratory of Immunology and General Pathology, Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy
| | - Gian Franco Gensini
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica, Milano, Italy
| | - Gaia Spinetti
- Laboratory of Cardiovascular Physiopathology-Regenerative Medicine, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica, Milano, Italy
| | | | - Antonino Bruno
- Laboratory of Innate Immunity, Unit of Molecular Pathology, Biochemistry and Immunology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica, Milano, Italy
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Drost JM, Cook CB, Spangehl MJ, Probst NE, Mi L, Trentman TL. A Plant-Based Dietary Intervention for Preoperative Glucose Optimization in Diabetic Patients Undergoing Total Joint Arthroplasty. Am J Lifestyle Med 2022; 16:150-154. [PMID: 35185437 PMCID: PMC8848119 DOI: 10.1177/1559827619879073] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/01/2023] Open
Abstract
Purpose. The purpose of this study was to assess the feasibility and effectiveness of a whole food plant-based diet (WFPBD) to improve day of surgery fasting blood glucose (FBG) among patients with type 2 diabetes (T2D). Patients and Methods. Ten patients with T2D scheduled for a total hip or total knee replacement were recruited. For 3 weeks preceding their surgeries, subjects were asked to consume an entirely WFPBD. Frozen WFPBD meals were professionally prepared and delivered to each participant for the 3 weeks prior to surgery. FBG was reassessed on the morning of surgery and compared with preintervention values. Compliance with the diet was assessed. Results. Mean age of subjects and reported duration of diabetes was 65 and 8 years, respectively, average hemoglobin A1c (HbA1c) was 6.6%, and 6 were women. Mean FBG decreased from 127 to 116 mg/dL (P = .2). Five of the subjects experienced improvement in glycemic control, with an average decline of 11 mg/dL. Conclusion. A WFPBD is a potentially effective intervention to improve glycemic control among patients with T2D during the period leading up to surgery. Future controlled trials on a larger sample of patients to assess the impact of a WFPBD on glycemic control and surgical outcomes are warranted.
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Affiliation(s)
- Jennifer M. Drost
- Jennifer M. Drost, MS, PA-C, Department of Anesthesiology, Mayo Clinic Arizona, 5777 East Mayo Boulevard, Phoenix, AZ 85054; e-mail:
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Ali Kazem T, Zeylabi F, Filayih Hassan A, Paridar P, Pezeshki SP, Pezeshki SMS. Diabetes mellitus and COVID-19: review of a lethal interaction from the cellular and molecular level to the bedside. Expert Rev Endocrinol Metab 2022; 17:1-19. [PMID: 34781797 DOI: 10.1080/17446651.2022.2002145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 10/25/2021] [Indexed: 01/08/2023]
Abstract
INTRODUCTION While the main mode of transmission of coronavirus disease 2019 (COVID-19) is close contact with other individuals, the presence of chronic underlying diseases such as Diabetes Mellitus (DM) increases the chance of hospitalization and mortality rate due to infection. AREAS COVERED To investigate the effects of COVID-19 infection in DM patients, we reviewed literature from Google Scholar search engine and PubMed database from '2013 to 2020' using the terms "COVID-19; SARS-CoV-2; Diabetes mellitus; obesity; Angiotensin-converting enzyme 2; ACE2; Insulin and Metformin. Evidence suggests that COVID-19 exacerbates the course of diabetes. Presence of pro-inflammatory conditions, increased expression of receptors, and more difficult control of glucose levels in diabetics COVID-19 patients are some of the problems that diabetic patients may face. Also, psychological problems caused by the COVID-19 epidemic in diabetic patients is one of the most important problems in these patients, which is less covered. EXPERT OPINION DM is a strong and independent risk factor with a poor prognosis, which increases the risk of COVID-19 infection, the need for emergency services, the rate of hospitalization in the intensive care unit and also increases the mortality rate of COVID-19 patients.
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Affiliation(s)
| | - Fatemeh Zeylabi
- Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | | | - Pouria Paridar
- Islamic Azad University, North-Tehran Branch, Tehran, Iran
| | - Seyedeh Pardis Pezeshki
- Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Seyed Mohammad Sadegh Pezeshki
- Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Reshad RAI, Riana SH, Chowdhury MAB, Moin AT, Miah F, Sarkar B, Jewel NA. Diabetes in COVID-19 patients: challenges and possible management strategies. THE EGYPTIAN JOURNAL OF BRONCHOLOGY 2021. [PMCID: PMC8642747 DOI: 10.1186/s43168-021-00099-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Background The recent pandemic of coronavirus disease 19 (COVID-19) has been causing intense stress among the global population. In the case of hospitalized and ICU-admitted COVID-19 patients with comorbidities, it has been observed that a major portion of them are diabetic. Therefore, researchers had indicated a link between diabetes mellitus (DM) and COVID-19. Furthermore, DM is a potential risk factor for the severity of COVID-19 cases. Thus, in this study, the correlation existing between diabetic patients and COVID-19 was summarized. Main body of the abstract Diabetic patients have a weaker immune system, less viral clearance rate, malfunctions of metabolic activity due to their high blood glucose level, and other associated problems. This does not increase the susceptibility for the patients to be infected with COVID-19. However, the severity of COVID-19 can worsen due to the comorbidity of DM. Short conclusion Proper management, appropriate use of drugs that do not increase the ACE2 expression, lowering blood glucose level, decreasing the susceptibility of SARS-CoV-2, and maintaining a healthy lifestyle could be effective.
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Zhang P, Yang CL, Du T, Liu YD, Ge MR, Li H, Liu RT, Wang CC, Dou YC, Duan RS. Diabetes mellitus exacerbates experimental autoimmune myasthenia gravis via modulating both adaptive and innate immunity. J Neuroinflammation 2021; 18:244. [PMID: 34702288 PMCID: PMC8549151 DOI: 10.1186/s12974-021-02298-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 10/17/2021] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Diabetes mellitus (DM) is a common concomitant disease of late-onset myasthenia gravis (MG). However, the impacts of DM on the progression of late-onset MG were unclear. METHODS In this study, we examined the immune response in experimental autoimmune myasthenia gravis (EAMG) rats with DM or not. The phenotype and function of the spleen and lymph nodes were determined by flow cytometry. The serum antibodies, Tfh cells, and germinal center B cells were determined by ELISA and flow cytometry. The roles of advanced glycation end products (AGEs) in regulating Tfh cells were further explored in vitro by co-culture assays. RESULTS Our results indicated clinical scores of EAMG rats were worse in diabetes rats compared to control, which was due to the increased production of anti-R97-116 antibody and antibody-secreting cells. Furthermore, diabetes induced a significant upregulation of Tfh cells and the subtypes of Tfh1 and Tfh17 cells to provide assistance for antibody production. The total percentages of B cells were increased with an activated statue of improved expression of costimulatory molecules CD80 and CD86. We found CD4+ T-cell differentiation was shifted from Treg cells towards Th1/Th17 in the DM+EAMG group compared to the EAMG group. In addition, in innate immunity, diabetic EAMG rats displayed more CXCR5 expression on NK cells. However, the expression of CXCR5 on NKT cells was down-regulated with the increased percentages of NKT cells in the DM+EAMG group. Ex vivo studies further indicated that Tfh cells were upregulated by AGEs instead of hyperglycemia. The upregulation was mediated by the existence of B cells, the mechanism of which might be attributed the elevated molecule CD40 on B cells. CONCLUSIONS Diabetes promoted both adaptive and innate immunity and exacerbated clinical symptoms in EAMG rats. Considering the effect of diabetes, therapy in reducing blood glucose levels in MG patients might improve clinical efficacy through suppressing the both innate and adaptive immune responses. Additional studies are needed to confirm the effect of glucose or AGEs reduction to seek treatment for MG.
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Affiliation(s)
- Peng Zhang
- Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766, Jingshi Road, Jinan, 250014, People's Republic of China.,Shandong Institute of Neuroimmunology, Jinan, 250014, People's Republic of China.,Shandong Key Laboratory for Rheumatic Disease and Translational Medicine, Jinan, 250014, People's Republic of China
| | - Chun-Lin Yang
- Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766, Jingshi Road, Jinan, 250014, People's Republic of China.,Shandong Institute of Neuroimmunology, Jinan, 250014, People's Republic of China.,Shandong Key Laboratory for Rheumatic Disease and Translational Medicine, Jinan, 250014, People's Republic of China
| | - Tong Du
- Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766, Jingshi Road, Jinan, 250014, People's Republic of China.,Shandong Institute of Neuroimmunology, Jinan, 250014, People's Republic of China.,Shandong Key Laboratory for Rheumatic Disease and Translational Medicine, Jinan, 250014, People's Republic of China
| | - Yu-Dong Liu
- Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766, Jingshi Road, Jinan, 250014, People's Republic of China.,Shandong Institute of Neuroimmunology, Jinan, 250014, People's Republic of China.,Shandong Key Laboratory for Rheumatic Disease and Translational Medicine, Jinan, 250014, People's Republic of China
| | - Meng-Ru Ge
- Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766, Jingshi Road, Jinan, 250014, People's Republic of China.,School of Medicine, Tongji University, Shanghai, 200092, People's Republic of China
| | - Heng Li
- Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766, Jingshi Road, Jinan, 250014, People's Republic of China.,Shandong Institute of Neuroimmunology, Jinan, 250014, People's Republic of China.,Shandong Key Laboratory for Rheumatic Disease and Translational Medicine, Jinan, 250014, People's Republic of China
| | - Ru-Tao Liu
- Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766, Jingshi Road, Jinan, 250014, People's Republic of China.,Shandong Institute of Neuroimmunology, Jinan, 250014, People's Republic of China.,Shandong Key Laboratory for Rheumatic Disease and Translational Medicine, Jinan, 250014, People's Republic of China
| | - Cong-Cong Wang
- Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766, Jingshi Road, Jinan, 250014, People's Republic of China.,Shandong Institute of Neuroimmunology, Jinan, 250014, People's Republic of China.,Shandong Key Laboratory for Rheumatic Disease and Translational Medicine, Jinan, 250014, People's Republic of China
| | - Ying-Chun Dou
- College of Basic Medical Sciences, Shandong University of Traditional Chinese Medicine, Jinan, 250355, People's Republic of China
| | - Rui-Sheng Duan
- Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766, Jingshi Road, Jinan, 250014, People's Republic of China. .,Shandong Institute of Neuroimmunology, Jinan, 250014, People's Republic of China. .,Shandong Key Laboratory for Rheumatic Disease and Translational Medicine, Jinan, 250014, People's Republic of China.
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Neuro-immune-metabolism: The tripod system of homeostasis. Immunol Lett 2021; 240:77-97. [PMID: 34655659 DOI: 10.1016/j.imlet.2021.10.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 09/30/2021] [Accepted: 10/08/2021] [Indexed: 11/20/2022]
Abstract
Homeostatic regulation of cellular and molecular processes is essential for the efficient physiological functioning of body organs. It requires an intricate balance of several networks throughout the body, most notable being the nervous, immune and metabolic systems. Several studies have reported the interactions between neuro-immune, immune-metabolic and neuro-metabolic pathways. Current review aims to integrate the information and show that neuro, immune and metabolic systems form the triumvirate of homeostasis. It focuses on the cellular and molecular interactions occurring in the extremities and intestine, which are innervated by the peripheral nervous system and for the intestine in particular the enteric nervous system. While the interdependence of neuro-immune-metabolic pathways provides a fallback mechanism in case of disruption of homeostasis, in chronic pathologies of continued disequilibrium, the collapse of one system spreads to the other interacting networks as well. Current review illustrates this domino-effect using diabetes as the main example. Together, this review attempts to provide a holistic picture of the integrated network of neuro-immune-metabolism and attempts to broaden the outlook when devising a scientific study or a treatment strategy.
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Leutner M, Kaleta M, Bellach L, Kautzky A, Thurner S, Klimek P, Kautzky-Willer A. Insulin as Monotherapy and in Combination with Other Glucose-Lowering Drugs Is Related to Increased Risk of Diagnosis of Pneumonia: A Longitudinal Assessment over Two Years. J Pers Med 2021; 11:jpm11100984. [PMID: 34683125 PMCID: PMC8537451 DOI: 10.3390/jpm11100984] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 09/21/2021] [Accepted: 09/24/2021] [Indexed: 01/22/2023] Open
Abstract
Objective: Patients with type 2 diabetes mellitus (T2DM) are at an increased risk of developing infectious diseases such as pneumonia. Hitherto, there has been uncertainty as to whether there is a relationship between different antidiabetic drug combinations and development of pneumonia in this specific cohort. Research Design and Methods: In this longitudinal retrospective study we used multiple logistic regression analysis to assess the odds ratios (ORs) of pneumonia during an observational period of 2 years in 31,397 patients with T2DM under previously prescribed stable antidiabetic drug combinations over a duration of 4 years in comparison to 6568 T2DM patients without drug therapy over 4 years adjusted for age, sex and hospitalization duration. Results: Of the 37,965 patients with T2DM, 3720 patients underwent stable monotherapy treatment with insulin (mean age: 66.57 ± 9.72 years), 2939 individuals (mean age: 70.62 ± 8.95 y) received stable statin and insulin therapy, and 1596 patients were treated with a stable combination therapy of metformin, insulin and statins (mean age: 68.27 ± 8.86 y). In comparison to the control group without antidiabetic drugs (mean age: 72.83 ± 9.96 y), individuals undergoing insulin monotherapy (OR: 2.07, CI: 1.54–2.79, p < 0.001); insulin and statin combination therapy (OR: 2.24, CI: 1.68–3.00, p < 0.001); metformin, insulin and statin combination therapy (OR: 2.27, CI: 1.55–3.31, p < 0.001); statin, insulin and dipeptidyl peptidase-4 inhibitor (DPP-IV inhibitor) combination therapy (OR: 4.31, CI: 1.80–10.33, p = 0.001); as well as individuals treated with metformin and sulfonylureas (OR: 1.70, CI: 1.08–2.69, p = 0.02) were at increased risk of receiving a diagnosis of pneumonia. Conclusions: Stable monotherapy with insulin, but also in combination with other antidiabetic drugs, is related to an increased risk of being diagnosed with pneumonia during hospital stays in patients with type 2 diabetes mellitus compared to untreated controls.
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Affiliation(s)
- Michael Leutner
- Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; (M.L.); (L.B.)
| | - Michaela Kaleta
- Section for Science of Complex Systems, CeMSIIS, Medical University of Vienna, Spitalgasse 23, A-1090 Vienna, Austria; (M.K.); (S.T.); (P.K.)
- Complexity Science Hub Vienna, Josefstaedter Strasse 39, A-1080 Vienna, Austria
| | - Luise Bellach
- Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; (M.L.); (L.B.)
| | - Alexander Kautzky
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, A-1090 Vienna, Austria;
| | - Stefan Thurner
- Section for Science of Complex Systems, CeMSIIS, Medical University of Vienna, Spitalgasse 23, A-1090 Vienna, Austria; (M.K.); (S.T.); (P.K.)
- Complexity Science Hub Vienna, Josefstaedter Strasse 39, A-1080 Vienna, Austria
- Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM 85701, USA
| | - Peter Klimek
- Section for Science of Complex Systems, CeMSIIS, Medical University of Vienna, Spitalgasse 23, A-1090 Vienna, Austria; (M.K.); (S.T.); (P.K.)
- Complexity Science Hub Vienna, Josefstaedter Strasse 39, A-1080 Vienna, Austria
| | - Alexandra Kautzky-Willer
- Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; (M.L.); (L.B.)
- Gender Institute, A-3571 Gars am Kamp, Austria
- Correspondence:
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Lu ZH, Yu WL, Sun Y. Multiple immune function impairments in diabetic patients and their effects on COVID-19. World J Clin Cases 2021; 9:6969-6978. [PMID: 34540952 PMCID: PMC8409204 DOI: 10.12998/wjcc.v9.i24.6969] [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: 01/28/2021] [Revised: 03/18/2021] [Accepted: 07/05/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2, poses a significant threat to public health worldwide, and diabetes is considered a risk factor for the rapid progression and poor prognosis of COVID-19. Limited immune function is a clinical feature of COVID-19 patients, and diabetes patients have defects in innate and adaptive immune functions, which may be an important reason for the rapid progression and poor prognosis of COVID-19 in patients with diabetes. We review the possible multiple effects of immune impairment in diabetic patients on the immune responses to COVID-19 to provide guidance for the diagnosis and treatment of diabetic patients with COVID-19.
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Affiliation(s)
- Zhong-Hua Lu
- Department of Critical Care Medicine, The Second Affiliated Hospital, Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Wei-Li Yu
- Department of Critical Care Medicine, The Second Affiliated Hospital, Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Yun Sun
- Department of Critical Care Medicine, The Second Affiliated Hospital, Anhui Medical University, Hefei 230601, Anhui Province, China
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Viurcos-Sanabria R, Escobedo G. Immunometabolic bases of type 2 diabetes in the severity of COVID-19. World J Diabetes 2021; 12:1026-1041. [PMID: 34326952 PMCID: PMC8311488 DOI: 10.4239/wjd.v12.i7.1026] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 04/16/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
The outbreak of coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). COVID-19 and type 2 diabetes (T2D) have now merged into an ongoing global syndemic that is threatening the lives of millions of people around the globe. For this reason, there is a deep need to understand the immunometabolic bases of the main etiological factors of T2D that affect the severity of COVID-19. Here, we discuss how hyperglycemia contributes to the cytokine storm commonly associated with COVID-19 by stimulating monocytes and macrophages to produce interleukin IL-1β, IL-6, and TNF-α in the airway epithelium. The main mechanisms through which hyperglycemia promotes reactive oxygen species release, inhibition of T cell activation, and neutrophil extracellular traps in the lungs of patients with severe SARS-CoV-2 infection are also studied. We further examine the molecular mechanisms by which proinflammatory cytokines induce insulin resistance, and their deleterious effects on pancreatic β-cell exhaustion in T2D patients critically ill with COVID-19. We address the effect of excess glucose on advanced glycation end product (AGE) formation and the role of AGEs in perpetuating pneumonia and acute respiratory distress syndrome. Finally, we discuss the contribution of preexisting endothelial dysfunction secondary to diabetes in the development of neutrophil trafficking, vascular leaking, and thrombotic events in patients with severe SARS-CoV-2 infection. As we outline here, T2D acts in synergy with SARS-CoV-2 infection to increase the progression, severity, and mortality of COVID-19. We think a better understanding of the T2D-related immunometabolic factors that contribute to exacerbate the severity of COVID-19 will improve our ability to identify patients with high mortality risk and prevent adverse outcomes.
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Affiliation(s)
| | - Galileo Escobedo
- Laboratorio de Proteómica, Dirección de Investigación, Hospital General de Mexico “Dr. Eduardo Liceaga”, Mexico City 06720, Mexico
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