scholarly journals Evaluation of the LTBP1 and Smad6 Genes Expression in Lung Tissue of Sulfur Mustard-exposed Individuals with Long-term Pulmonary Complications

2019 ◽  
Author(s):  
Somayeh Mami ◽  
Sara Ghaffarpour ◽  
Soghrat Faghihzadeh ◽  
Tooba Ghazanfari
Keyword(s):  
Lung Tissue ◽  
Negative Feedback ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Sulfur Mustard ◽  
Control Group ◽  
Main Role ◽  
Expression Levels ◽  
And Control

Sulfur mustard (SM) exposure injures different organs such as the lungs and leads to short and long term complications Transforming growth factor beta (TGF-β) has the main role in altering fibroblast activities linked to airways remodeling. Latency TGF beta binding proteins 1 (LTBP1 facilitates localization of TGF-β in the extracellular matrix. Mothers against decapentaplegic homolog 6 (Smad6) negatively regulates TGF-β signaling, thus establishing a main negative feedback loop. In this study, we investigated the expression of LTBP1 and Smad6 in the lung tissues of SM-exposed and control individuals. Lung formalin-fixed paraffin-embedded (FFPE) blocks of SM-exposed (20 samples) and control groups (20 samples) were collected from archival pathology department of several general hospitals. The total mRNA of lung FFPE tissues was extracted. Quality of the extracted mRNA was evaluated by an Agilent Bio analyzer and RNA was quantified using a Nano Drop. LTBP1 and Smad6 expression levels were evaluated by real-time PCR. LTBP1 expression levels did not change between the two groups (p=0.626), howeverSmad6 expression levels were significantly higher (2.6 fold) in SM-exposed individuals compared to the control group (p=0.001). Our results revealed that Smad6 may be involved in lung tissue remodeling process in SM-exposed patients. Smad6 regulates fibrotic alterations in lung tissue and its function as negative feedback mechanisms in TGF-β.

Serum Concentration of Thyroid Hormones Long-Term After Sulfur Mustard Exposure

2019 ◽  
Author(s):  
Sakine MOAIEDMOHSENI ◽  
Tooba GHAZANFARI ◽  
Ensie Sadat MIRSHARIF ◽  
Nayere ASKARI ◽  
Zuhair MOHAMMAD HASSAN ◽  
...  
Keyword(s):  
Cohort Study ◽  
Thyroid Hormones ◽  
Sulfur Mustard ◽  
Clinical Manifestations ◽  
Exposed Group ◽  
Control Group ◽  
Gene Expressions ◽  
Historical Cohort ◽  
And Control

Background: Despite several reports on the clinical manifestations of sulfur mustard (SM) intoxication, there is no study on serum concentrations of thyroid hormones long-term after SM exposure. In this study, the changes in thyroid functioning parameters 20 yr after SM exposure were evaluated. Methods: This study is a part of a larger historical cohort study conducted in 2007 following 20 years of the exposure to SM, called Sardasht–Iran cohort study (SICS). We (SICS) comprised an SM–exposed group from Sardasht City, West Azerbaijan Province, Iran (n=169 as hospitalized group and n=203 as non-hospitalized exposed group); and control participants were selected from Rabat, a town near Sardasht (n=126). Peripheral blood samples were taken in fasting state and then the sera were separated. T4, T3, TSH, antithyroglobulin (anti–Tg), and antithyroid peroxidase (anti–TPO) concentrations in the sera were measured by the ELISA method. Results: The mean of T3 concentration was significantly higher in the exposed than control group (0.88 ± 0.26 nmol/L vs 0.8 ± 0.25 nmol/L, P<0.001). The levels of TSH, T4, and T3up were not significantly different between the exposed and control groups. Thyroglobulin level was significantly higher in the exposed non-hospitalized group (56.07 ± 140.22 µg/L vs 17.66 ± 41.49 µg/L, P=0.004), but the level of anti–Tg and anti–TPO showed no significant differences between the two groups. Conclusion: More studies are needed on the alterations in thyroid hormones, their gene expressions, and mechanisms involved in SM exposure to clarify the causes of these alterations.

scholarly journals Expression of miR-15b-5p, miR-21-5p, and SMAD7 in Lung Tissue of Sulfur Mustard-exposedIndividuals with Long-term Pulmonary Complications

2019 ◽  
Author(s):  
Sahar Salimi ◽  
Farshid Noorbakhsh ◽  
Soghrat Faghihzadeh ◽  
Sara Ghaffarpour ◽  
Tooba Ghazanfari
Keyword(s):  
Lung Tissue ◽  
Inflammatory Responses ◽  
Sulfur Mustard ◽  
Pulmonary Complications ◽  
Cytokine Signaling ◽  
Control Group ◽  
Expression Levels ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Smad7 Expression

Sulfur mustard (SM)-exposed individuals develop late pulmonary complications, which are associated with chronic inflammation and fibrotic changes in the lung tissue. MicroRNAs are known to act as important regulators of inflammatory responses, including inflammation and fibrosis-related cytokine signaling. In this study, we investigated the expression miR-15b-5p and miR-21-5p, two regulators of TGF-β signaling, as well as their target molecule, SMAD7, in lung tissues from SM-exposed and control individuals. Total RNA was extracted from formalin-fixed paraffin-embedded (FFPE) lung tissue biopsies obtained during surgery from SM-exposed (n=20) or control (n=20) cases. Quality of the extracted RNA was evaluated by an Agilent Bioanalyzer and RNA was quantified using a NanoDrop. MiR-21-5p, miR-15b-5p and SMAD7 expression levels were measured by real-time RT-PCR.miR-21-5p expression levels were significantly decreased (2.7 fold) in the lung tissues from SM-exposed individuals compared with tissues obtained from the control group(p=0.02). There were no significant differences in miR-15b-5p expression levels between the two groups(p=0.94). Interestingly, SMAD7 expression levels were significantly higher (5.8 fold) in SM-exposed individuals’ lung tissues compared with the control group(p=0.045).Our data indicate that exposure to sulfur mustard affects the expression of miR-21-5p as well as its target, SMAD7, in lung tissues many years after exposure. Considering the role of SMAD7 in the regulation of TGF-β signaling, these changes might point to a potential mechanism by which SM-exposure regulates inflammatory/fibrotic alterations in lung tissue.

scholarly journals Does co-transplantation of mesenchymal and spermatogonial stem cells improve reproductive efficiency and safety in mice?

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Prashant Kadam ◽  
Elissavet Ntemou ◽  
Jaime Onofre ◽  
Dorien Van Saen ◽  
Ellen Goossens
Keyword(s):  
Stem Cells ◽  
Germ Cells ◽  
Transforming Growth Factor Beta ◽  
Dna Methyltransferase ◽  
Transforming Growth Factor ◽  
Spermatogonial Stem Cells ◽  
Reproductive Efficiency ◽  
Control Group ◽  
Low Efficiency

Abstract Background Spermatogonial stem cell transplantation (SSCT) is a promising therapy in restoring the fertility of childhood cancer survivors. However, the low efficiency of SSCT is a significant concern. SSCT could be improved by co-transplanting transforming growth factor beta 1 (TGFβ1)-induced mesenchymal stem cells (MSCs). In this study, we investigated the reproductive efficiency and safety of co-transplanting spermatogonial stem cells (SSCs) and TGFβ1-induced MSCs. Methods A mouse model for long-term infertility was used to transplant SSCs (SSCT, n = 10) and a combination of SSCs and TGFβ1-treated MSCs (MSi-SSCT, n = 10). Both transplanted groups and a fertile control group (n = 7) were allowed to mate naturally to check the reproductive efficiency after transplantation. Furthermore, the testes from transplanted males and donor-derived male offspring were analyzed for the epigenetic markers DNA methyltransferase 3A (DNMT3A) and histone 4 lysine 5 acetylation (H4K5ac). Results The overall tubular fertility index (TFI) after SSCT (76 ± 12) was similar to that after MSi-SSCT (73 ± 14). However, the donor-derived TFI after MSi-SSCT (26 ± 14) was higher compared to the one after SSCT (9 ± 5; P = 0.002), even after injecting half of the number of SSCs in MSi-SSCT. The litter sizes after SSCT (3.7 ± 3.7) and MSi-SSCT (3.7 ± 3.6) were similar but differed significantly with the control group (7.6 ± 1.0; P < 0.001). The number of GFP+ offspring per litter obtained after SSCT (1.6 ± 0.5) and MSi-SSCT (2.0 ± 1.0) was also similar. The expression of DNMT3A and H4K5ac in germ cells of transplanted males was found to be significantly reduced compared to the control group. However, in donor-derived offspring, DNMT3A and H4K5ac followed the normal pattern. Conclusion Co-transplanting SSCs and TGFβ1-treated MSCs results in reproductive efficiency as good as SSCT, even after transplanting half the number of SSCs. Although transplanted males showed lower expression of DNMT3A and H4K5ac in donor-derived germ cells, the expression was restored to normal levels in germ cells of donor-derived offspring. This procedure could become an efficient method to restore fertility in a clinical setup, but more studies are needed to ensure safety in the long term.

Fibrogenic cytokine levels in bronchoalveolar lavage aspirates 15 years after exposure to sulfur mustard

2004 ◽  
Vol 287 (6) ◽  
pp. L1160-L1164 ◽  
Author(s):  
Reza Aghanouri ◽  
Mostafa Ghanei ◽  
Jafar Aslani ◽  
Hossein Keivani-Amine ◽  
Ferdos Rastegar ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Transforming Growth Factor ◽  
Sulfur Mustard ◽  
Interstitial Fibrosis ◽  
Control Group ◽  
Case Group ◽  
War Veterans ◽  
Test Kit ◽  
And Control ◽  
Tgf Β1

Over 100,000 Iranian war veterans suffer from chronic effects of mustard gas exposure. Sulfur mustard was used by Iraq during the Iraqi-imposed war on Iran (between 1980 and 1988). The major complaints of these patients are mild interstitial fibrosis and bronchiolitis. We aimed to determine the state of fibrosis progression and assessed transforming growth factor (TGF)-β1 levels in pulmonary samples and in bronchoalveolar lavage (BAL) aspirates. A total of 126 war veterans confirmed for lung disease were assessed and compared with three control groups: 1) 64 veterans not exposed to chemical agents, 2) 12 idiopathic pulmonary fibrosis civilian patients, and 3) 33 normal persons. BAL was performed via a flexible fiber-optic bronchoscope and the standard manual method. Total protein was measured by Bradford assay, and samples were corrected with regard to coefficients. Samples were concentrated 15-fold by lyophilization and resolubilization. Samples were double-checked using an ELISA test kit. The Mann-Whitney test was used for the data analysis using commercial software. We detected that significant differences between TGF-β1 levels between the case group and control group 1 ( P = 0.001) and control group 3 ( P = 0.003). No significant differences were found between the case group and control group 2 ( P = 0.57). Inflammation and fibrotic processes in lung tissue of patients exposed to sulfur mustard may be progressive so IFN-γ may be a useful drug to these patients' treatment.

Relationship of MMP-2 and TGF-β2 levels in human vitreous with axial length

2020 ◽  
Vol 1 (1) ◽  
pp. 37-41
Author(s):  
Ting-Ting Zhao ◽  
◽  
Jing Jin ◽  
Shu-Nong Xie ◽  
Ying Fan ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Axial Length ◽  
High Myopia ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Matrix Metalloproteinase 2 ◽  
Control Group ◽  
Significant Difference ◽  
And Control ◽  
Relationship Of

AIM: To investigate the relationship of matrix metalloproteinase-2 (MMP-2) and transforming growth factor-beta 2 (TGF-β2) levels in human vitreous with axial length (AL) of patients with high myopia. METHODS: The concentrations of MMP-2 and TGF-β2 levels were tested by enzyme-linked immunosorbnent assay (ELISA). Fifty-five human vitreous samples of 55 patients were collected during vitrectomy surgery, and were divided into two groups according to their spherical equivalent (SE) and AL. High myopia group (25 cases): AL≥26.00 mm, and control group or non-high myopia group (30 cases): AL<26.00 mm. RESULTS: The MMP-2 levels in vitreous of high myopia group (96.87±55.95 ng/mL) was significantly higher than that of control group (77.24±41.81 ng/mL, P<0.05), but not correlated with AL (r=0.088, P=0.544). While the vitreous TGF-β2 concentration was negatively correlated with AL (r=-0.344, P=0.014), and there was significant difference of TGF-β2 vitreous levels between high myopia group (3729.08±1890.88 pg/mL) and control group (3926.00± 1333.88 pg/mL, P<0.05). CONCLUSION: MMP-2 and TGF-β2 in human vitreous may play a critical role in human high myopia development, and the TGF-β2 appears to be associated with AL.

scholarly journals Nebulized Heparin Attenuates Pulmonary Coagulopathy and Inflammation through Alveolar Macrophages in a Rat Model of Acute Lung Injury

2017 ◽  
Vol 117 (11) ◽  
pp. 2125-2134 ◽  
Author(s):  
Laura Chimenti ◽  
Marta Camprubí-Rimblas ◽  
Raquel Guillamat-Prats ◽  
Maria Gomez ◽  
Jessica Tijero ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Lung Tissue ◽  
Alveolar Macrophages ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Coagulation Cascade ◽  
Control Group ◽  
Proinflammatory Mediators

Objective Alveolar macrophages play a key role in the development and resolution of acute respiratory distress syndrome (ARDS), modulating the inflammatory response and the coagulation cascade in lungs. Anti-coagulants may be helpful in the treatment of ARDS. This study investigated the effects of nebulized heparin on the role of alveolar macrophages in limiting lung coagulation and inflammatory response in an animal model of acute lung injury (ALI). Methods Rats were randomized to four experimental groups. In three groups, ALI was induced by intratracheal instillation of lipopolysaccharide (LPS) and heparin was nebulized at constant oxygen flow: the LPS/Hep group received nebulized heparin 4 and 8 hours after injury; the Hep/LPS/Hep group received nebulized heparin 30 minutes before and 4 and 8 hours after LPS-induced injury; the LPS/Sal group received nebulized saline 4 and 8 hours after injury. The control group received only saline. Animals were exsanguinated 24 hours after LPS instillation. Lung tissue, bronchoalveolar lavage fluid (BALF) and alveolar macrophages isolated from BALF were analysed. Results LPS increased protein concentration, oedema and neutrophils in BALF as well as procoagulant and proinflammatory mediators in lung tissue and alveolar macrophages. In lung tissue, nebulized heparin attenuated ALI through decreasing procoagulant (tissue factor, thrombin–anti-thrombin complexes, fibrin degradation products) and proinflammatory (interleukin 6, tumour necrosis factor alpha) pathways. In alveolar macrophages, nebulized heparin reduced expression of procoagulant genes and the effectors of transforming growth factor beta (Smad 2, Smad 3) and nuclear factor kappa B (p-selectin, CCL-2). Pre-treatment resulted in more pronounced attenuation. Conclusion Nebulized heparin reduced pulmonary coagulopathy and inflammation without producing systemic bleeding, partly by modulating alveolar macrophages.

scholarly journals The Anti-PD-1/PD-L1 Immunotherapy for Gastric Esophageal Cancer: A Systematic Review and Meta-Analysis and Literature Review

2021 ◽  
Vol 28 ◽  
pp. 107327482199743
Author(s):  
Ke Chen ◽  
Xiao Wang ◽  
Liu Yang ◽  
Zheling Chen
Keyword(s):  
Overall Survival ◽  
Esophageal Cancer ◽  
Survival Rate ◽  
Meta Analysis ◽  
Response Rates ◽  
Control Group ◽  
Term Survival ◽  
Long Term Survival ◽  
And Control

Background: Treatment options for advanced gastric esophageal cancer are quite limited. Chemotherapy is unavoidable at certain stages, and research on targeted therapies has mostly failed. The advent of immunotherapy has brought hope for the treatment of advanced gastric esophageal cancer. The aim of the study was to analyze the safety of anti-PD-1/PD-L1 immunotherapy and the long-term survival of patients who were diagnosed as gastric esophageal cancer and received anti-PD-1/PD-L1 immunotherapy. Method: Studies on anti-PD-1/PD-L1 immunotherapy of advanced gastric esophageal cancer published before February 1, 2020 were searched online. The survival (e.g. 6-month overall survival, 12-month overall survival (OS), progression-free survival (PFS), objective response rates (ORR)) and adverse effects of immunotherapy were compared to that of control therapy (physician’s choice of therapy). Results: After screening 185 studies, 4 comparative cohort studies which reported the long-term survival of patients receiving immunotherapy were included. Compared to control group, the 12-month survival (OR = 1.67, 95% CI: 1.31 to 2.12, P < 0.0001) and 18-month survival (OR = 1.98, 95% CI: 1.39 to 2.81, P = 0.0001) were significantly longer in immunotherapy group. The 3-month survival rate (OR = 1.05, 95% CI: 0.36 to 3.06, P = 0.92) and 18-month survival rate (OR = 1.44, 95% CI: 0.98 to 2.12, P = 0.07) were not significantly different between immunotherapy group and control group. The ORR were not significantly different between immunotherapy group and control group (OR = 1.54, 95% CI: 0.65 to 3.66, P = 0.01). Meta-analysis pointed out that in the PD-L1 CPS ≥10 sub group population, the immunotherapy could obviously benefit the patients in tumor response rates (OR = 3.80, 95% CI: 1.89 to 7.61, P = 0.0002). Conclusion: For the treatment of advanced gastric esophageal cancer, the therapeutic efficacy of anti-PD-1/PD-L1 immunotherapy was superior to that of chemotherapy or palliative care.

The Effect of Telerehabilitation on Quality of Life, Exercise Capacity, and Spirometry Indexes in Patients with Chronic Obstructive Pulmonary Disease in Masih Daneshvari Hospital

2021 ◽  
Author(s):  
Somayeh Ghadimi ◽  
Atefeh Fakharian ◽  
Mohsen Abedi ◽  
Reyhaneh Zahiri ◽  
Mahsan Norouz Afjeh ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Control Group ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
And Control

Background: Chronic Obstructive Pulmonary Disease (COPD) leads to limited activity and reduced quality of life. Treatment of this disease is a long-term process that requires the cooperation of patients in monitoring and treatment. Methods: In the present study which was conducted from April 2019 to March 2021 in Masih Daneshvari Hospital, Tehran, Iran, 75 patients were randomly divided into telerehabilitation and control groups. Patients in the control group received pulmonary rehabilitation including respiratory, isometric, and aerobic exercises for 8 weeks, three times per week. In the second group, patients were given a lung rehabilitation booklet and asked to repeat the exercises three times a week for four weeks according to a specific schedule. In addition, patients installed Behzee care application on the mobile phone that recorded various indicators such as heart rate, SpO2, dyspnea, fatigue, and daily activities. This application reminded the patient of the program every day and at a specific time. Finally, the patients’ conditions were compared in the two groups after 8 weeks using CAT and mMRC questionnaires and 6-Minute Walk (6MW) exercise indices as well as spirometry tests. Results: In all four indicators (6MW, CAT,  and mMRC questionnaires as well as spirometry), patients showed improvement after rehabilitation (p<0.001). This improvement was significantly higher in the telemedicine group compared to the other group (p<0.01). Conclusion: The use of telerehabilitation in COPD patients is effective in improving spirometry indices, quality of life, as well as activity and sports indices.

scholarly journals Long Term Stabilization of Expanding Aortic Aneurysms by a Short Course of Cyclosporine A through Transforming Growth Factor-Beta Induction

PLoS ONE ◽  
2011 ◽  
Vol 6 (12) ◽  
pp. e28903 ◽  
Author(s):  
Jianping Dai ◽  
Stéphanie Michineau ◽  
Grégory Franck ◽  
Pascal Desgranges ◽  
Jean-Pierre Becquemin ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cyclosporine A ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Aortic Aneurysms ◽  
Short Course ◽  
Growth Factor Beta

scholarly journals What is the impact of methotrexate on liver in patients with juvenile idiopathic arthritis? Results of liver SWE performed in a single centre

2021 ◽  
Author(s):  
Vildan Güngörer ◽  
Mehmet Öztürk ◽  
Mustafa Yasir Özlü ◽  
Şükrü Arslan
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Shear Wave Elastography ◽  
Term Therapy ◽  
Control Group ◽  
Significant Difference ◽  
Group 2 ◽  
Long Term Therapy ◽  
And Control ◽  
The Impact

ABSTRACT Objectives Long-term therapy with low-dose methotrexate (MTX) is widely used in treatment of rheumatic diseases, in children. The purpose of this study was to evaluate liver elasticity in patients with juvenile idiopathic arthritis (JIA) who received MTX and compare the results with control group. Methods Liver elasticity was evaluated with shear wave elastography (SWE) technique in 25 patients aged 3–17 years who were followed up with JIA and received MTX and compared with 25 healthy controls of the same age and weight. Factors that had an effect on liver elasticity were examined. Results The mean SWE value of patients was 2.64 ± 2.13 m/s and 24.10 ± 18.50 kPa, whereas 1.83 ± 0.16 m/s and 10.09 ± 1.83 kPa in control group. There was a significant difference in liver elasticity in the patient and control groups. When the patients were evaluated as Group 1 (&lt; 1000 mg) and Group 2 (≥ 1000 mg) according to the cumulative MTX dose, no significant difference was obtained. There was positive correlation between liver elasticity and weekly MTX dose and age. Conclusions Our study revealed that liver elasticity significantly decreased in patients who received MTX when compared with the control group. The elastography technique will be understood better over time and used safely in many areas.

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