RESUMO
Exosomes derived from adipose tissue-derived mesenchymal stem cells (AD-MSCs) have immunomodulatory effects of T-cell inflammatory response and reduction of clinical symptoms on streptozotocin-induced of the type-1 diabetes mellitus (T1DM). Beside control group and untreated T1DM mice, a group of T1DM mice was treated with intraperitoneal injections of characterized exosomes derived from autologous AD-MSCs. Body weight and blood glucose levels were measured during the procedure. Histopathology and immunohistochemistry were used for evaluation of pancreatic islets using hemotoxylin and eosin (H&E) staining and anti-insulin antibody. Isolated splenic mononuclear cells (MNCs) were subjected to splenocytes proliferation assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, immunophenotyping of regulatory T cells and cytokines. A significant increase in the levels of interleukin-4 (IL-4), IL-10, and transforming growth factor-ß, and a decrease in the levels of IL-17 and interferon-γ in concordance with the significant increase in the Treg cell ratio in splenic MNCs (P < 0.05) was shown in T1DM mice treated with AD-MSC's exosomes as compared to T1DM untreated mice. This amelioration of autoimmune reaction after treatment of T1DM mice with the AD-MSC exosomes was confirmed with a significant increase in islets using H&E staining and Immunohistochemistry analyses. As expected, body weight, blood glucose levels in a survival of T1DM mice treated with AD-MSC's exosomes were maintained stable in comparison to untreated T1DM mice. It can be concluded that AD-MSC's exosomes exert ameliorative effects on autoimmune T1DM through increasing regulatory T-cell population and their products without a change in the proliferation index of lymphocytes, which makes them more effective and practical candidates.
Assuntos
Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/metabolismo , Exossomos/metabolismo , Células-Tronco Mesenquimais/citologia , Animais , Proliferação de Células/efeitos dos fármacos , Imuno-Histoquímica , Ilhotas Pancreáticas/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Células-Tronco Mesenquimais/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Estreptozocina/farmacologia , Linfócitos T Reguladores/efeitos dos fármacosRESUMO
Background and Aims: Due to the recent emergence of COVID-19, the exact pathology of this disease has not been determined. Therefore, this study evaluated the frequency of neurological symptoms in patients with COVID-19. Methods: This cross-sectional study was conducted on 2200 in patients with COVID-19 who were selected from an educational hospital in Sanandaj, Iran, from April 2020 to March 2021. The research samples were selected by census, all patients with COVID-19 were admitted to the hospital. The data collection tool was a checklist of the studied variables (dizziness, headache, and impaired consciousness) prepared by the researchers based on the specialists' opinions. The researcher completed these checklists based on the patients' hospitalization records. The data were analyzed by descriptive and analytical statistical tests using SPSS Software Version 20. The quantitative variables were compared using the independent t-test. The χ 2 test was also used to compare qualitative variables. A p Value of less than 0.05 was considered statistically significant. Results: The mean age of the patients was 57.41 years old, of whom 53.1% were male. The average blood oxygen level of the patients was 88.10%, and most disease symptoms were related to shortness of breath and cough, with a frequency of 24.3%. In addition, 20.8% of patients needed hospitalization in intensive care unit. The highest frequency of central and peripheral nervous system manifestations was related to headache, ageusia (loss of sense of taste), hyposmia (A decreased sense of smell and anosmia (The complete loss of smell). Finally, 15.3% of patients died, and 84.7% recovered. The analytical findings showed a significant relationship between the disease outcome and patients' dizziness, consciousness disorder, seizure and ageusia. There was a significant relationship between gender and headache in patients. There was a significant difference between the mean age and oxygen level with central and peripheral nervous system manifestations (dizziness, headache, impaired consciousness, smell disorder) and the disease outcome in patients. Conclusion: The pathophysiology of COVID-19 virus infection involving the central nervous system is not fully understood. Neurological symptoms of this virus include delirium, headache, decreased level of consciousness, and seizures. Identifying the symptoms and mechanisms of neurological complications of COVID-19 is necessary for proper screening and complete treatment because a patient infected by COVID-19 may not show respiratory failure signs but may be a carrier. A complete and accurate knowledge of the symptoms and complications of this infection for proper screening of patients to prevent transmission and spread of this disease is critically needed.
RESUMO
Fibrosing pneumonia (FP) is classified into usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP), each having its own etiology and prognosis. Both types of FP are progressive and chronic conditions with distinct etiologies. Cytokines and inflammatory mediators play critical roles in the pathogenesis of FP. Among them, the role of transforming growth factor beta-1 (TGF-ß1) and modulators triggering fibrosis are not well understood. In this study, the expression of triggering receptor expressed on myeloid cells-1 (TREM-1) as a stimulator for the production of TGF-ß1 and also CD4+CD25+Foxp3+ regulatory cells were investigted in FP patients. Sixteen UIP, 14 NSIP and 4 pulmonary fibrosis following Mycobacterium tuberculosis (TB) infection patients, were compared with 12 healthy controls. The frequency of blood CD14+TGF-ß1+ and CD14+TREM1+-gated monocytes and CD4+CD25+Foxp3+ regulatory T cells (Treg), as well as the plasma levels of TGF-ß1 and IL10 were measured. Fibrosis patients compared to healthy controls had a greater frequency of CD14+TGF-ß1+ [15.9 (0.2-88.2) vs. 0.6 (0.2-11.0)] and CD14+TREM1+ [21.1 (2.3-91.2) vs. 10.3 (3.1-28.6)]-gated monocytes, and CD4+CD25+Foxp3+ [1.2 (0.3-3.6) vs. 0.2 (0.1-0.4)]-gated lymphocytes. Plasma TGF-ß1 were also significantly increased in patients with fibrosis compared to healthy controls [9316.2 (±5554.4) vs. 3787.5 (±2255.6)]. These results confirm the importance of TGF-ß1 and TREM1 in pulmonary fibrosis. It seems that this reciprocal cycle in healthy people is modulated by the production of IL10 by Treg cells, thus limiting fibrosis, as observed in patients following TB infection. Further investigations are recommended to evaluate possible immunomodulatory mechanisms defects in pulmonary fibrosis.
Assuntos
Fibrose Pulmonar , Humanos , Fibrose Pulmonar/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Interleucina-10/metabolismo , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Linfócitos T Reguladores , Fatores de Transcrição Forkhead/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
AIM: Considering the allergic basis of Eosinophilic esophagitis (EoE), this study was conducted to evaluate peripheral blood Tregs in children with EoE. BACKGROUND: Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of gastrointestinal tract. Regulatory T cells (Tregs) have a confirmed role in allergic disorders. METHODS: Children with EoE, gastroesophageal reflux disease (GERD) and healthy controls (HC) (10 subjects in each group) were recruited after diagnosis by a pediatric gastroenterologist and allergist. After obtaining informed written consent, peripheral blood was obtained. Peripheral blood mononuclear cells were isolated by Ficoll gradient centrifugation. Flowcytometry was used to enumerate peripheral blood Tregs (CD4 +CD25 +FOXP3+ gated lymphocytes were considered as Tregs). RESULTS: CD4+ gated lymphocytes significantly increased in EoE and GERD groups compared to HC group (p= 0.018). Tregs also was significantly increased in EoE in comparison to HC group (p=0.016). There were no statistically significant differences in Tregs of EoE as compared to GERD subjects (p=0.085). CONCLUSION: Peripheral blood Tregs increase in patients with EoE as compared to healthy controls, which may be indicative of a feedback mechanism to regulate inflammatory responses.
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Autophagy is a major regulatory cellular mechanism which gives the cell an ability to cope with some of the destructive events that normally occur within a metabolically living cell. This is done by maintaining the cellular homeostasis, clearance of damaged organelles and proteins and recycling necessary molecules like amino acids and fatty acids. There is a wide array of factors that influence autophagy in the state of health and disease. Disruption of these mechanisms may not only give rise to several autophagy-related disease, but also it can occur as the result of intracellular changes induced during disease pathogenesis causing exacerbation of the disease. Our knowledge is increasing regarding the role of autophagy and its mechanisms in the pathogenesis of various neurodegenerative diseases such as multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease and Amyotrophic lateral sclerosis. Indeed, getting to know about the pathways of autophagy and its regulation can provide the basis for designing therapeutic interventions. In the present paper, we review the pathways of autophagy, its regulation and the possible autophagy-targeting interventions for the treatment of neurodegenerative disorders.
Assuntos
Autofagia/fisiologia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Ensaios Clínicos como Assunto/métodos , Humanos , Doenças Neurodegenerativas/genética , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Doença de Parkinson/patologiaRESUMO
BACKGROUND: Allogeneic islet transplantation could be an ideal alternative therapy for Type 1 Diabetes Mellitus (T1DM). Adipose Tissue-derived Mesenchymal Stem Cells (AT-MSCs) characterized by immunomodulatory and protective effects may have the potential to improve the outcome of this highly immunogenic transplant. METHODS: Syngenic AT-MSCs along with allograft islets embedded in hydrogelic composite and transplanted intraperitoneally in Streptozotocin (STZ) induced diabetic C57BL/6 mice. RESULTS: In vitro experiments of co-imbedded islets and AT-MSCs in a hydrogel revealed AT-MSCs are able to significantly increase insulin secretion. During a 32 days of post-transplant period, blood glucose monitoring showed a decrease from over 400mg/dl to less than 150mg/dl and at the end of 32 days, mice have been dissected and assessed. Graft histopathology demonstrated that hydrogel makes an artificial immune isolation site and AT-MSCs contribute greatly to the reduction of the immune cells infiltration. Analyses of mononuclear cells isolated from Mesenteric Lymph Nodes (MLNs) and spleen showed that AT-MSCs co-transplanted with allograft decreased pro-inflammatory cytokines and increased regulatory cytokines (for both MLNs and spleen) and regulatory T cells (Treg) population (only for MLNs). In addition, real time-PCR assays revealed that transcript levels of IDO, iNOS, and PDX1, significantly increased in allograft islets in the presence of AT-MSCs. CONCLUSIONS: according to results, this investigation indicates that AT-MSCs can be regarded as promising complementary candidates for engineered-cell therapy using hydrogel composites in islet transplantation.