Thymic microenvironmental alterations in experimentally induced diabetes

Nagib, Patrícia Resende Alo; Gameiro, Jacy; Stivanin-Silva, Luiz Guilherme; Arruda, Maria Sueli Parreira de; Villa‐Verde, Déa Maria Serra; Savino, Wilson; Verinaud, Liana

doi:10.1016/j.imbio.2010.02.001

Cited by 23 publications

(27 citation statements)

References 35 publications

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“…Although fibroblast migration has been shown to involve α2β1 integrin [44, 45], the increase in VLA-2 expression due to exposure to 1 μg/mL AuNPs could not prevent reduction of migration. This is consistent with emerging evidence showing that increase or decrease in integrin expression may not directly affect migration, as shown by Nagib et al [46]. In that study, thymocytes from diabetic mice that expressed lower VLA-5 and VLA-6 levels did not show altered migration ability in vitro, indicating that only lower integrin expression on the cell surface is not sufficient to hinder migration.…”

Section: Discussionsupporting

confidence: 92%

Metallic nanoparticles reduce the migration of human fibroblasts in vitro

et al. 2017

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Nanoparticles have extremely wide applications in the medical and biological fields. They are being used in biosensors, local drug delivery, diagnostics, and medical therapy. However, the potential effects of nanoparticles on target cell and tissue function, apart from cytotoxicity, are not completely understood. Thus, the aim of this study was to investigate the in vitro effects of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) on human fibroblasts with respect to their interaction with the extracellular matrix and in cell migration. Immunofluorescence analysis revealed that treatment with AgNPs or AuNPs decreased collagen and laminin production at all the concentrations tested (0.1, 1, and 10 μg/mL). Furthermore, cytofluorometric analysis showed that treatment with AgNPs reduced the percentage of cells expressing the collagen receptor very late antigen 2, α2β1 integrin (VLA-2) and the laminin receptor very late antigen 6, α6β1 integrin (VLA-6). In contrast, AuNP treatment increased and decreased the percentages of VLA-2-positive and VLA-6-positive cells, respectively, as compared to the findings for the controls. Analysis of cytoskeletal reorganization showed that treatment with both types of nanoparticles increased the formation of stress fibres and number of cell protrusions and impaired cell polarity. Fibroblasts exposed to different concentrations of AuNPs and AgNPs showed reduced migration through transwell chambers in the functional chemotaxis assay. These results demonstrated that metal nanoparticles may influence fibroblast function by negatively modulating the deposition of extracellular matrix molecules (ECM) and altering the expression of ECM receptors, cytoskeletal reorganization, and cell migration.Electronic supplementary materialThe online version of this article (doi:10.1186/s11671-017-1982-3) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Metallic nanoparticles reduce the migration of human fibroblasts in vitro

et al. 2017

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“…Interestingly, the thymus microenvironment alters frequently in DM patients [3]. In this case, the patient was positive for anti-GAD and ICA, which supported the diagnosis of MG accompanied with type 1 DM.…”

Section: Discussionsupporting

confidence: 69%

Thymectomy Cures Diabetes Mellitus and Ameliorates Myasthenia Gravis in a Patient with Thymus Hyperplasia and Hyperthyroidism: Report of a Case

et al. 2015

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Myasthenia gravis (MG) is a devastating autoimmune disease that involves the acetylcholine receptor (AchR) in the postsynaptic membrane of the neuromuscular junction. It is not uncommon for MG to accompany with other autoimmune diseases and complicate with multiple organ dysfunction. Here, we report on an 18-year-old female patient with a rare case of MG concomitant with thymus hyperplasia, diabetes mellitus, and hyperthyroidism. After full excision of the hyperplastic thymus gland, the patient's muscle weakness was greatly improved and her blood glucose level was restored to normal at the 6-month follow-up.Keywords Myasthenia gravis . Diabetes . Thymus hyperplasia . Hyperthyroidism . Thymectomy CaseAn 18-year-old female, without positive family history, complained of right eyelid drooping, diplopia, and masticatory muscle weakness for 3 months. Her symptoms were alleviated with pyridostigmine bromide (120 mg/day). She was admitted with a 3-day history of dyspnea and myasthenia of the limbs. Physical examination revealed tachycardia (139/ min), reduced muscle tension of her limbs (level IV), abated tendinous reflex, and a positive fatigue test and a neostigmine test. Her Osserman classification was myasthenia gravis (MG) type IIB. Pyridostigmine bromide (120 mg/day) and methylprednisolone (500 mg/day) helped reduce her symptoms. Laboratory analyses indicated that her serum potassium was 4.62 mmol/L (reference interval [RI], 3.5-5.5 mmol/L), fasting plasma glucose was 8.0 mmol/L, urinary glucose was (++), her 75 g/2 h oral glucose tolerance test (OGTT) was 14.2 mmol/L, thyroid-stimulating hormone (TSH) was 0.007 μIU/mL (RI, 0.27-4.2 μIU/mL), free T4 was 63.59 pmol/L (RI, 12.0-22.0 pmol/L), free T3 was 11.60 pmol/L (RI, 3.1-6.8 pmol/L), thyroid globulin antibody was 30.45 IU/mL (RI <115.0 IU/mL), anti-thyromicrosomal antibody (ATM-Ab) was 61.73 IU/mL (RI<35.0 IU/mL), thyroid peroxidase antibodies (TPO-Ab) were 396.98 IU/mL (RI<300.0 IU/mL), and TSH receptor antibody (TR-Ab) was 17.2 IU/mL (RI< 9.0 IU/mL). In addition, she was positive for acetylcholine receptor antibodies (AChR-Ab), serum antibodies of glutamic acid decarboxylase (anti-GAD) and islet cell antibodies (ICA), and negative for insulin autoantibody (IAA). The thyroid ultrasound revealed multiple small follicles in both lobes. Chest computed tomography (CT) depicted a soft tissue in the thymus area of the anterior-superior mediastinum, which was considered thymus hyperplasia (Fig. 1a). The electromyogram suggested decreased muscle contraction and inconsistent or blocked fiber transmission. After a multidisciplinary round, the patient was treated with a full thymectomy under general anesthesia. Histological examination confirmed thymus hyperplasia (Fig. 2). The patient was finally diagnosed with MG accompanied with thymus gland hyperplasia, type I diabetes mellitus (DM), and hyperthyroidism.The patient had a MG crisis after surgery, which was managed with tracheotomy/ventilator-assisted breathing, pyridostigmine bromide, and glucocorticoids. Her...

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“…The thymus is a primary lymphoid organ in which the differentiation of T lymphocytes occurs ( 1 ) . It may also be considered as an organ of the endocrine system and, therefore, an endocrine gland that secretes hormones and other soluble factors controlling the production and maturation of T lymphocytes ( 2 ) , and regulating the activity and interactions of T cells in peripheral tissues ( 3 ) .…”

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confidence: 99%

Effect of a probiotic fermented milk on the thymus in Balb/c mice under non-severe protein–energy malnutrition

Núñez

Galdeano

Carmuega³

et al. 2013

Br J Nutr

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Protein -energy malnutrition (PEM) causes a significant impairment of the immune system, the thymus being one of the most affected organs. It has been demonstrated that the administration of probiotic fermented milk (PFM) recovered the intestinal barrier, histological alterations and mucosal and systemic immune functions in a non-severe malnutrition model using BALB/c mice. The aim of the present study was to evaluate, in the same model of malnutrition, the effect of a PFM added to a re-nutrition diet on the recovery of the thymus, analysing histological and functional alterations caused by malnutrition. Mice were undernourished and divided into three groups according to the dietary supplement received during re-nutrition: milk, PFM or its bacterial-free supernatant (BFS). They were compared with well-nourished and malnourished mice. PFM was the most effective re-nutrition supplement to improve the histology of the thymus, decreasing cellular apoptosis in this organ and recovering the percentage of CD4 þ /CD8 2 single-positive thymocytes. Immature doublepositive thymocytes were increased in the malnourished control (MC). The production of different cytokines in the thymus was increased in mice given PFM, compared with the mice that received other dietary supplements and MC. Mice given the BFS presented an improvement in the thymus similar to those that received milk. We demonstrated the importance of the whole PFM supplementation on the histological and functional recovery of the thymus in a non-severe PEM model.

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Thymic microenvironmental alterations in experimentally induced diabetes

Cited by 23 publications

References 35 publications

Metallic nanoparticles reduce the migration of human fibroblasts in vitro

Metallic nanoparticles reduce the migration of human fibroblasts in vitro

Thymectomy Cures Diabetes Mellitus and Ameliorates Myasthenia Gravis in a Patient with Thymus Hyperplasia and Hyperthyroidism: Report of a Case

Effect of a probiotic fermented milk on the thymus in Balb/c mice under non-severe protein–energy malnutrition

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