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 ◽  
...  

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.

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Shahram Bamdad ◽  
Fatemeh Sanie-Jahromi ◽  
Marzieh Alamolhoda ◽  
Nasrin Masihpour ◽  
Mohammad-Hossein Karimi

Background. To investigate the association of glutathione s-transferase omega 2 (GSTO2) (142N > D) and transforming growth factor-β1 (TGF-β1) (869T > C) gene polymorphisms on the pathogenesis of two common types of glaucoma (including primary open-angle glaucoma (POAG) and chronic angle-closure glaucoma (CACG)) in the Iranian population. Methods. A total of 100 glaucoma patients (60% males and 40% females with an age mean ± SD of 34.66 ± 14.25 years; 56 cases of POAG and 44 cases of CACG) were enrolled in this study. GSTO2 (142N > D) and TGF-β1 (869T > C) polymorphisms were evaluated by PCR-based methods in patients and controls. Results. At locus GSTO2 (142N > D), the odds of ND genotype with respect to DD and NN genotypes were 1.55 and 2.08 times higher in POAG and CACG patients compared to those of patients in the control group (95% CI1: 0.80–2.98; 95% CI2: 1.00–4.33) which was statistically significant in CACG patients. However, the odds of DD and NN genotypes against the reference genotype in two patients group were not statistically significant as compared to those of patients in the control group. There was a significant association between the ND genotype and male patients (OR = 2.28, 95% CI: 1.06–4.92). The analysis of TGF-β1 (869T > C) polymorphisms showed no significant difference between the genotypes of TGF-β1 (869T > C) polymorphisms in patients and control groups; however, the CT genotype of TGF-β1 significantly differed between female controls and patients (OR = 0.42, 95% CI: 0.18–0.96). Conclusion. The presented results revealed that there was a significant association between the ND genotype of GSTO2 and the pathogenesis of glaucoma. Furthermore, this genotype can be considered as a sex-dependent genetic risk factor for the development of glaucoma. In contrast, the CT genotype of TGF-β1 is suggested to be a protective genetic factor against the pathogenesis of glaucoma.


Author(s):  
Somayeh Mami ◽  
Sara Ghaffarpour ◽  
Soghrat Faghihzadeh ◽  
Tooba Ghazanfari

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.


2021 ◽  
Author(s):  
Yong Chen ◽  
Xiaohui Lin ◽  
Yanfang Zheng ◽  
Wenzhen Yu ◽  
Fan Lin ◽  
...  

Abstract BackgroundDendrobium mixture (DMix) is an effective treatment for diabetic nephropathy (DN), but the underlying molecular mechanism remains unclear. In this study, we investigated whether DMix regulates the transforming growth factor-β1 (TGF-β1)/Smads signal transduction pathway. MethodsTwenty-four db/db mice were randomly divided into three groups: the model, DMix, and gliquidone groups, while eight db/m mice were selected as the normal control group. The drug was administered by continuous gavage for 8 weeks. Body weight (BW), kidney weight (KW), kidney index, fasting blood glucose (FBG), blood lipid, 24-hour urinary albumin excretion rate, blood urea nitrogen, and serum creatinine levels were measured. Pathological changes in the renal tissue were observed using a light microscope. Real-time quantitative PCR and immunohistochemical staining were used to detect mRNA expression of TGF-β1 and alpha-smooth muscle actin (α-SMA) genes and proteins, respectively, in renal tissues. TGF-β1, Smad2, p-Smad2, Smad3, p-Smad3, and α-SMA expression levels were measured using western blotting. ResultsDMix significantly reduced FBG level, BW, KW, and blood lipid level, and improved renal function in db/db mice. Histopathology showed that DMix alleviated glomerular mesangial cell proliferation and renal interstitial fibrosis in db/db mice. Additionally, DMix reduced protein and mRNA expression of TGF-β1 and α-SMA, and inhibited Smad2 and Smad3 phosphorylation. ConclusionsThe findings suggest that DMix may inhibit renal fibrosis and delay the progression of DN by regulating the TGF-β1/Smads signaling pathway. Key words: Diabetic nephropathy, Dendrobium mixture, TGF-β1/Smads signaling pathway


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Natalia Zaicova ◽  
Tatiana Sudareva ◽  
Vladimir Dlin ◽  
Lilia Sinitsina ◽  
Anatolii Korsunskiy

Abstract Background and Aims to determine the diagnostic value of profibrogenic cytokines of transforming growth factor (TGF-β1) and angiotensin II (AngII) in urine to detect the severity of tubulointerstitial fibrosis in children with vesicoureteral reflux (VUR) depending on the therapeutic approach. Method 117 patients aged 3 to 16 years (mean age 10.2 ± 4.5, 70.1% of girls) with VUR were examined. The control group consisted of 20 healthy children. All children underwent a complete nephrological examination. The levels of TGF-β1 and AngII were determined in morning urine using the ELISA method and counted for urine creatinine. To identify the severity of the lesion of the renal parenchyma, a static DMSA scintigraphy was performed. Results depending on the therapeutic approach, the children were divided into 2 groups: 1 gr. - children on conservative treatment (63.2%), 2 gr. - children, after surgical correction of VUR (36.8%). In each group, 3 subgroups were identified depending on the development of tubulo-interstitial fibrosis according to DMSA: A subgr. - without signs of sclerosis (15.4%), B subgr. - 1-2 foci (44.74%) and C subgr - > 3-4 foci of sclerosis (40.1%). All patients with VUR had a high urinary excretion of TGF-β1/Cr and AngII/Cr when compared with the control group (p<0.05). Regardless of the therapeutic approach, in subgroups A (without foci of sclerosis) and B (1-2 foci of sclerosis), patients had a statistically significantly lower level of excretion of these cytokines when compared with patients from subgroup C (p <0.05). No significant difference was found in the urinary excretion of TGF-β1/Cr and AngII/Cr depending on the therapeutic approach. Conclusion we established a reliable dependence of the excretion of TGF-β1/Cr and AngII /Cr in the urine on the severity of tubulo-interstitial fibrosis according to DMSA scintigraphy in children with VUR. At the same time, we did not note the dependence of the excretion of TGF-β1/Cr and AngII/Cr in the urine on the method of the therapeutic approach. Therefore, the study of the excretion of TGF-β1/Cr and AngII/Cr in the urine as non-invasive markers can be used as a criterion for the progression of nephropathy in VUR, regardless of treatment methods.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yong Chen ◽  
Xiaohui Lin ◽  
Yanfang Zheng ◽  
Wenzhen Yu ◽  
Fan Lin ◽  
...  

Dendrobium mixture (DMix) is an effective treatment for diabetic nephropathy (DN), but the molecular mechanism underlying its action remains unclear. In this study, we investigated whether DMix regulates the transforming growth factor-β1 (TGF-β1)/Smads signal transduction pathway. Twenty-four db/db mice were randomly divided into three groups: the model, DMix, and gliquidone groups, while eight db/m mice were selected as the normal control group. The drug was administered by continuous gavage for 8 weeks. Body weight (BW), kidney weight (KW), kidney index, fasting blood glucose (FBG), blood lipid, 24-hour urinary albumin excretion rate, blood urea nitrogen, and serum creatinine levels were measured. Pathological changes in the renal tissue were observed under a light microscope. Real-time quantitative PCR and immunohistochemical staining were used to detect the mRNA and protein expression levels of TGF-β1 and alpha-smooth muscle actin (α-SMA), respectively, in renal tissues. TGF-β1, Smad2, p-Smad2, Smad3, p-Smad3, and α-SMA expression levels were measured using western blotting. The results showed that DMix significantly reduced the FBG level, BW, KW, and blood lipid level and improved renal function in db/db mice. Histopathology showed that DMix alleviated glomerular mesangial cell proliferation and renal interstitial fibrosis in db/db mice. Additionally, DMix reduced the protein and mRNA expression levels of TGF-β1 and α-SMA and inhibited Smad2 and Smad3 phosphorylation. We conclude that DMix may inhibit renal fibrosis and delay the progression of DN by regulating the TGF-β1/Smads signaling pathway.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Asmaa Ali ◽  
Mona Hasan ◽  
Shaimaa Hamed ◽  
Amir Elhamy

Abstract Background Around 25% of the world population was affected by the metabolic-related fatty liver disorder. Hepatic steatosis is frequently observed in conjunction with hypertension, obesity comorbidities, and diabetes. We evaluate the hepatic steatosis frequency found in chest CT exams of COVID-19-positive cases compared to non-infected controls and evaluate the related increased prevalence and severity of COVID. Results Our research includes 355 subjects, 158 with positive PCR for COVID-19 (case group) and 197 with negative PCR and negative CT chest (control group). The mean age in the positive group was 50.6 ± 16 years, and in the control, it was 41.3 ± 16 years (p < 0.001). Our study consists of 321 men (90.5%) and 34 women (9.5%). The number of males in both cases and control groups was greater. In the case group, 93% men vs. 6.9% women, while in controls, 88.3% men vs.11.6% women, p < 0.001. CT revealed normal results in 55.5% of individuals (i.e., CORADs 1) and abnormal findings in 45.5% of participants (i.e., CORADs 2–5). In abnormal scan, CO-RADs 2 was 13.92%, while CO-RADs 3–4 were 20.89% of cases. CO-RADs 5 comprised 65.19% of all cases. Approximately 42.6% of cases had severe disease (CT score ≥ 20), all of them were CO-RADs 5. The PCR-positive class had a greater prevalence of hepatic steatosis than controls (28.5% vs.12.2%, p < 0.001). CO-RADs 2 represented 11.1%, CO-RADs 3–4 represented 15.6%, and CO-RADs 5 represented 73.3% in the hepatic steatosis cases. The mean hepatic attenuation value in the case group was 46.79 ± 12.68 and in the control group 53.34 ± 10.28 (p < 0.001). When comparing patients with a higher severity score (CT score ≥ 20) to those with non-severe pneumonia, it was discovered that hepatic steatosis is more prevalent (73.2% vs. 26.8%). Conclusions Steatosis was shown to be substantially more prevalent in COVID-19-positive individuals. There is a relation among metabolic syndrome, steatosis of the liver, and obesity, as well as the COVID-19 severity.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jingwei Cai ◽  
Guixing Jiang ◽  
Yuelong Liang ◽  
Yangyang Xie ◽  
Junhao Zheng ◽  
...  

Abstract Objectives This study was designed to evaluate the safety and effectiveness of a two-hand technique combining harmonic scalpel (HS) and laparoscopic Peng’s multifunction operative dissector (LPMOD) in patients who underwent laparoscopic hemihepatectomy (LHH). Methods We designed and conducted a case-control study nested in a prospectively collected laparoscopic liver surgery database. Patients who underwent LHH for liver parenchyma transection using HS + LPMOD were defined as cases (n = 98) and LPMOD only as controls (n = 47) from January 2016 to May 2018. Propensity score matching (1:1) between the case and control groups was used in the analyses. Results The case group had significantly less intraoperative blood loss in milliliters (169.4 ± 133.5 vs. 221.5 ± 176.3, P = 0.03) and shorter operative time in minutes (210.5 ± 56.1 vs. 265.7 ± 67.1, P = 0.02) comparing to the control group. The conversion to laparotomy, postoperative hospital stay, resection margin, the mean peak level of postoperative liver function parameters, bile leakage rate, and others were comparable between the two groups. There was no perioperative mortality. Conclusions We demonstrated that the two-handed technique combing HS and LPMOD in LHH is safe and effective which is associated with shorter operative time and less intraoperative blood loss compared with LPMOD alone. The technique facilitates laparoscopic liver resection and is recommended for use.


Author(s):  
Wagner Vargas Souza Lino ◽  
André Luis Lacerda Bachi ◽  
José Arruda Mendes Neto ◽  
Gabriel Caetani ◽  
Jônatas Bussador do Amaral ◽  
...  

Abstract Introduction Combination of chronic inflammation and an altered tissue remodeling process are involved in the development of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Studies demonstrated that mesenchymal stem cells expressing the progenitor gene CD133 were involved in a significant reduction of the chronic inflammatory process in the polypoid tissue. Objective To evaluate the levels of CD133 (Prominin-1) in nasal polypoid tissue and its correlation with interleukin-8 (IL-8) and transforming growth factor β1 (TGF-β1). Methods A total of 74 subjects were divided in the following groups: control group (n = 35); chronic rhinosinusitis with nasal polyps nonpresenting comorbid asthma and aspirin intolerance (CRSwNPnonAI) group (n = 27); and chronic rhinosinusitis with nasal polyps presenting comorbid asthma and aspirin intolerance (CRSwNPAI) group (n = 12). Histologic analysis and also evaluation of the concentration of CD133, IL-8, and TGF-β1 by enzyme-linked immunosorbent assay (ELISA) kits were performed in nasal tissue obtained from nasal polypectomy or from middle turbinate tissue. Results Higher eosinophilic infiltration was found in both CRSwNP groups by histologic analysis. Lower levels of TGF-β1 and IL-8 were observed in both CRSwNP groups when compared with the control group, whereas the CD133 levels were significantly reduced only in the CRSwNPnonAI group compared with the control group. Conclusion It was demonstrated that the nasal mucosa presenting polyposis showed a significant reduction of CD133 levels, and also that this reduction was significantly correlated with the reduction of TGF-β1 levels, but not with IL-8 levels. Therefore, these findings may be involved in the altered inflammatory and remodeling processes observed in the nasal polyposis.


2020 ◽  
Vol 21 (19) ◽  
pp. 7374
Author(s):  
Gilberto Y. Nakama ◽  
Sabrina Gonzalez ◽  
Polina Matre ◽  
Xiaodong Mu ◽  
Kaitlyn E. Whitney ◽  
...  

Recent efforts have focused on customizing orthobiologics, such as platelet-rich plasma (PRP) and bone marrow concentrate (BMC), to improve tissue repair. We hypothesized that oral losartan (a TGF-β1 blocker with anti-fibrotic properties) could decrease TGF-β1 levels in leukocyte-poor PRP (LP-PRP) and fibrocytes in BMC. Ten rabbits were randomized into two groups (N = 5/group): osteochondral defect + microfracture (control, group 1) and osteochondral defect + microfracture + losartan (losartan, group 2). For group 2, a dose of 10mg/kg/day of losartan was administrated orally for 12 weeks post-operatively. After 12 weeks, whole blood (WB) and bone marrow aspirate (BMA) samples were collected to process LP-PRP and BMC. TGF-β1 concentrations were measured in WB and LP-PRP with multiplex immunoassay. BMC cell populations were analyzed by flow cytometry with CD31, CD44, CD45, CD34, CD146 and CD90 antibodies. There was no significant difference in TGF-β1 levels between the losartan and control group in WB or LP-PRP. In BMC, the percentage of CD31+ cells (endothelial cells) in the losartan group was significantly higher than the control group (p = 0.008), while the percentage of CD45+ cells (hematopoietic cells-fibrocytes) in the losartan group was significantly lower than the control group (p = 0.03).


2017 ◽  
Vol 41 (S1) ◽  
pp. S359-S360 ◽  
Author(s):  
D. Sabic ◽  
A. Sabic

The aim of this study was to analyse frequency of embitterment in war veterans with Posttraumatic stress disorder (PTSD) as well as the potential impact of embitterment on the development of chronic PTSD.Patients and methodsIt was analyzed 174 subjects (from Health Center Zivinice/mental health center) through a survey conducted in the period from March 2015 to June 2016, of which 87 war veterans with PTSD and control subjects 87 war veterans without PTSD. The primary outcome measure was the post-traumatic embitterment disorder self-rating scale (PTED Scale) who contains 19 items designed to assess features of embitterment reactions to negative life events. Secondary efficacy measures included the clinician-administered PTSD scale–V (CAPS), the PTSD checklist (PCL), the combat exposure scale (CES), the Hamilton depression rating scale (HAM-D), the Hamilton anxiety rating scale (HAM-A) and the World health organization quality of life scale (WHOQOL-Bref). All subjects were male. The average age of patients in the group war veterans with PTSD was 52.78 ± 5.99. In the control group, average age was 51.42 ± 5.98. Statistical data were analyzed in SPSS statistical program.ResultsComparing the results, t-tests revealed significant difference between group veterans with PTSD and control group (t = −21,21, P < 0.0001). War veterans group with PTSD (X = 51.41, SD = 8,91), control group (X = 14.39, SD = 13.61).ConclusionEmbitterment is frequent in war veterans with PTSD.Disclosure of interestThe authors have not supplied their declaration of competing interest.


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