scholarly journals The Association Between β-Dystroglycan in Airway Smooth Muscle and Eosinophils in Allergic Asthma

Inflammation ◽  
2021 ◽  
Author(s):  
Suhayla H. Shareef ◽  
Kawa Amin ◽  
Christer Janson

Abstract Allergic asthma (AA) is a complex disorder with heterogeneous features of airway hyperresponsiveness, inflammation, and remodeling. The increase of airway smooth muscle (ASM) mass is a fundamental component of bronchial remodeling in AA, yet the pathophysiological mechanisms and clinical outcomes associated with ASM modulation are still elusive. The objective of this study is to compare the expression level of β-dystroglycan (β-DG) in ASM in AA subjects and a healthy control group and to investigate the relationship between eosinophils and β-DG in ASM in patients with AA. Thirteen AA patients and seven control subjects were analyzed for the ASM area and eosinophil cells. Bronchial biopsies were stained by β-DG and eosinophil cationic protein (ECP) using immunohistochemistry. The proportion of ASM with β-DG staining was greater in those with AA than in the healthy control group (mean (95% CI) (28.3% (23.8–32.7%) vs. 16.4% (14.1–18.5%), P < 0.0001). The number of ECP positive cells was higher in patients with AA than in the control group (4056 (3819–4296) vs. 466 (395–537) cells/mm2P < 0.0001). In AA, the number of ECP positive cells was significantly correlated to the β-DG expression in ASM (r = 0.77, P = 0.002). There is an increased β-DG expression in ASM and a higher number of ECP positive cells in the bronchial biopsy of those with AA than those in the control group. The increased expression of β-DG in ASM in AA subjects correlates with the number of eosinophils, suggesting a role for this cell in airway remodeling in AA.

2021 ◽  
Author(s):  
Qi Feng Huang ◽  
Tang Deng ◽  
Lihua Li ◽  
Jin Qian ◽  
Qi Li ◽  
...  

Abstract Background: Airway smooth muscle cells (ASMC) can produce a variety of cytokine during inflammation, causing changes in the components of the extracellular matrix, which are related to airway remodeling. Midkine (MK) can promote the chemotaxis of various inflammatory cells and release inflammatory factors. Whether Notch and Midkine together affect the proliferation and apoptosis of airway smooth muscle cells is unclear.Objective: To study the mechanism of Midkine on LPS-induced acute lung injury caused by airway smooth muscle cells.Methods: Airway smooth muscle cells were cultured in vitro and divided into 5 groups: control group, lipopolysaccharide group (LPS), Non-targeted siRNA group, MKsiRNA group, Notch inhibitor group (LY411575). The cell proliferation level was detected by CCK-8. The apoptosis level was detected by flow cytometry. The changes of cytokine in the Midkine/Notch2 signaling pathway were detected by Westernblot, qPCR and cellular immunofluorescence.Results: Midkine and Notch2 were highly expressed in the LPS group. MKsiRNA can effectively block the expression of Midkine induced by LPS while down-regulating the expression of Notch2. This result is the same as that of Notch inhibitor (LY411575). Exogenous Midkine promoted the proliferation of airway smooth muscle cells and reduced the rate of apoptosis in the LPS group. When the expression of Midkine was blocked, the proliferation of airway smooth muscle cells in the LPS group was significantly reduced, while apoptosis increased. Inhibiting the expression of Notch, the proliferation of airway smooth muscle cells in the LPS group decreased, and apoptosis increased.Conclusions: Midkine/Notch2 signaling pathway plays an important role in regulating airway smooth muscle cell proliferation and apoptosis in airway inflammation.


2021 ◽  
Author(s):  
Bohan Wang ◽  
Lingling Tang ◽  
Suofang Shi ◽  
Ying Yang ◽  
Xianhong Sun ◽  
...  

Abstract BackgroundAsthma is a common chronic respiratory disease. Qufeng Xuanbi Formula (QFXBF), a Chinese herbal decoction, has shown efficiency for the management of asthma. The purpose of current study is to investigate the potential therapeutic effects of QFXBF for the treatment of asthma both in vitro and in vivo. MethodsPDGF-induced ASMCs proliferation model and MTT assay have been applied for exploring the effects of QFXBF on the proliferation of ASMCs. Moreover, 40 female BALB/c mice were randomly divided into five groups: control group, OVA group, High QFXBF group, Low QFXBF group, and dexamethasone (DEX) group (n = 8 per group). The mouse allergic asthma model has been established by intranasally administered ovalbumin (OVA) sensitization method. Morphological changes of the lung tissue have been examined by hematoxylin and eosin (H&E) staining and Masson’s staining. Finally, the protein expressions of α-SMA, PCNA, p-MEK1/2, MEK1/2, p-ERK1/2, and ERK1/2 in ASMCs and lung tissue were determined by western blotting and immunofluorescent staining assays. ResultsPDGF induced significant increase in viability of ASMCs. Compared with mice in control group, the airway walls and airway smooth muscle of mice in OVA group mice thickened, and the inflammatory cells around the bronchus increased significantly. Moreover, administration of QFXBF markedly inhibited the proliferation of ASMCs and alleviated the pathologic changes induced by OVA. Furthermore, the protein expressions of p-ERK1/2, p-MEK1/2, PCNA, and α-SMA were significantly increased in OVA-treated mice and PDGF-treated ASMCs. Finally, treatment of QFXBF also significantly decreased the protein expression of p-ERK1/2, p-MEK1/2, α-SMA and PCNA. ConclusionQFXBF can inhibit the proliferation of ASMCs via suppressing the MEK/ERK signaling in PDGF-induced ASMCs and OVA-induced mice.


1999 ◽  
Vol 5 (4) ◽  
pp. 664-675
Author(s):  
O. M. Badr El Din ◽  
I. H. El Sawy ◽  
O. E. El Azzouni ◽  
M. M. A. Badr El Din ◽  
A. M. Salem

To study the value of eosinophil cationic protein [ECP] as a serological marker of disease activity in childhood bronchial asthma, ECP levels were measured in 20 healthy control children and 25 asthmatic children, during and 2 weeks after acute exacerbation. The mean serum ECP level of all asthmatic patients, during and after exacerbation, was significantly higher than the control group and was significantly higher during attacks than 2 weeks after their termination. ECP levels were highest in severe attacks, but did not differ between mild and moderate attacks. ECP levels in asthmatic patients 2 weeks after mild and moderate attacks were comparable to normal; after severe attacks levels remained higher than normal. Measurement of serum ECP will be helpful in determining asthma activity and deciding the use of anti-asthma drugs


2021 ◽  
Vol 9 (5) ◽  
pp. 672-677
Author(s):  
Esraa Wathah ◽  
◽  
Saleem Khteer Al-Hadraawy ◽  

The primary goal of this study was to determine the function of eosinophil cationic protein in iron status in patients infected with Enterobius vermicularis. For this, a total of 583 suspected patients and thirty healthy people of the same age who have visited the AL-Zahra maternity and pediatrics laboratory, AL-Hakeem hospital, AL-Sajad hospital AL-Fruit al-Awsat hospital, and AL-Munadira hospital in AL-Najaf province from July 2020 to June 2021 were screened. The presence of E. vermicularis eggs was estimated by using the saline wet mount technique from faeces samples of all respondents. Blood samples were collected from the 60 positive and 30 healthy control group and centrifuged at 3000 rpm for 5 minutes to separate serum, which was then collected in sterile tubes. Each serum sample was divided into three parts and stored in the deep freezer at -20°C until the serological test was performed. The level of ECP, iron and ferritin in enterobiasis patients was estimated from the isolated blood serum. According to the Manufacturer Company instructions, the concentration of two biomarkers (ECP, Ferritin) in serum samples was determined using the ELISA technique (Human reader, Germany). While the concentration of iron was evaluated using a colourimetric method. In comparison to the control group, the concentration of ECP was reported significantly higher (P<0.05) in the E. vermiculris infected patients while the concentration of serum iron and ferritin was significantly decreased. The results of the current study can be concluded that E. vermicularis infection changes the serum ECP, iron, and ferritin concentration.


2016 ◽  
Vol 86 (1-2) ◽  
pp. 9-17 ◽  
Author(s):  
Bekir Ucan ◽  
Mustafa Sahin ◽  
Muyesser Sayki Arslan ◽  
Nujen Colak Bozkurt ◽  
Muhammed Kizilgul ◽  
...  

Abstract.The relationship between Hashimoto’s thyroiditis and vitamin D has been demonstrated in several studies. The aim of the present study was to evaluate vitamin D concentrations in patients with Hashimoto’s thyroiditis, the effect of vitamin D therapy on the course of disease, and to determine changes in thyroid autoantibody status and cardiovascular risk after vitamin D therapy. We included 75 patients with Hashimoto’s thyroiditis and 43 healthy individuals. Vitamin D deficiency is defined as a 25-hydroxy vitamin D (25(OH)D3) concentration less than 20ng/mL. Vitamin D deficient patients were given 50.000 units of 25(OH)D3 weekly for eight weeks in accordance with the Endocrine Society guidelines. All evaluations were repeated after 2 months of treatment. Patients with Hashimoto’s thyroiditis had significantly lower vitamin D concentrations compared with the controls (9.37±0.69 ng/mL vs 11.95±1.01 ng/mL, p < 0.05, respectively). Thyroid autoantibodies were significantly decreased by vitamin D replacement treatment in patients with euthyroid Hashimoto’s thyroiditis. Also, HDL cholesterol concentrations improved in the euthyroid Hashimoto group after treatment. The mean free thyroxine (fT4) concentrations were 0.89±0.02 ng/dL in patients with Hashimoto’s thyroiditis and 1.07±0.03 ng/dL in the healthy control group (p < 0.001). The mean thyroid volumes were 7.71±0.44 mL in patients with Hashimoto’s thyroiditis and 5.46±0.63 mL in the healthy control group (p < 0.01). Vitamin D deficiency is frequent in Hashimoto’s thyroiditis and treatment of patients with this condition with Vitamin D may slow down the course of development of hypothyroidism and also decrease cardiovascular risks in these patients. Vitamin D measurement and replacement may be critical in these patients.


2020 ◽  
Vol 22 (9) ◽  
pp. 657-662 ◽  
Author(s):  
Mustafa Celik ◽  
Alper Şen ◽  
İsmail Koyuncu ◽  
Ataman Gönel

Aim and Objective:: To determine the mechanisms present in the etiopathogenesis of nasal polyposis. It is not clear whether amino acids contribute in a causal way to the development of the disease. Therefore, the aim of this study was to determine the plasma-free amino acid profile in patients with nasal polyposis and to compare the results with a healthy control group. Materials and Methods:: This was a prospective controlled study that took place in the Otolaryngology Department at the Harran University Faculty of Medicine between April 2017 and April 2018. Plasmafree amino acid profile levels were studied in serum samples taken from a patient group and a healthy control group. Patients who were diagnosed with bilateral diffuse nasal polyposis and were scheduled for surgical interventions were included in this study. Individuals whose age, gender, and body mass index values were compatible with that of the patient group and who did not have any health problems were included in the control group. All the participants whose levels of plasma-free amino acid were thought to be affected by one or more of the following factors were excluded from the study: smoking and alcohol use, allergic rhinitis presence, the presence of acute or chronic sinusitis, a history of endoscopic sinus surgery, unilateral nasal masses, a history of chronic drug use, systemic or topical steroid use in the last three months for any reason, and liver, kidney, hematological, cardiovascular, metabolic, neurological, or psychiatric disorders or malignancies. Results: In patients with nasal polyposis, 3-methyl histidine (3-MHIS: nasal polyposis group (ng) = 3.22 (1.92 – 6.07); control group (cg) = 1.21 (0.77 – 1.68); p = 0.001); arginine (arg: ng = 98.95 (70.81 – 117.75); cg = 75.10 (54.49 – 79.88); p = 0.005); asparagine (asn: ng = 79.84 (57.50 – 101.44); cg = 60.66 (46.39 – 74.62); p = 0.021); citrulline (cit: ng = 51.83 (43.81 – 59.78); cg = 38.33 (27.81 – 53.73); p = 0.038); cystine (cys: ng = 4.29 (2.43 – 6.66); cg = 2.41 (1.51 – 4.16); p = 0.019); glutamic acid (glu: ng = 234.86 (128.75 – 286.66); cg = 152.37 (122.51 – 188.34); p = 0.045); histidine (his: ng = 94.19 (79.34 – 113.99); cg = 74.80 (62.76 – 98.91); p = 0.018); lysine (lys: ng = 297.22 (206.55 – 371.25); cg = 179.50 (151.58 – 238.02); p = 0.001); ornithine (ng = 160.62 (128.36 – 189.32); cg = 115.91 (97.03 – 159.91); p = 0.019); serine (ser: ng = 195.15 (151.58 – 253.07); cg = 83.07 (67.44 – 92.44); p = 0.001); taurine (tau: ng = 74.69 (47.00 – 112.13); cg = 53.14 (33.57 – 67.31); p = 0.006); tryptophan (trp: ng = 52.31 (33.81 – 80.11); cg = 34.44 (25.94 – 43.07); p = 0.005), homocitrulline (ng = 1.75 (1.27 – 2.59); cg = 0.00 (0.00 – 0.53); p = 0.001); norvaline (ng = 6.90 (5.61 – 9.18); cg = 4.93 (3.74 – 7.13); p = 0.021); argininosuccinic acid (ng = 14.33 (10.06 – 25.65); cg = 12.22 (5.77 – 16.87) p = 0.046); and plasma concentrations were significantly higher than in the healthy control group (p <0.05). However, the gamma-aminobutyric acid (gaba: ng = 0.16 (0.10 – 0.24); cg = 0.21 (0.19 – 0.29); p = 0.010) plasma concentration was significantly lower in the nasal polyposis group than in the healthy control group. Conclusion: In this study, plasma levels of 15 free amino acids were significantly higher in the nasal polyposis group than in the healthy control group. A plasma level of 1 free amino acid was found to be significantly lower in the nasal polyposis group compared to the healthy control group. Therefore, it is important to determine the possibility of using the information obtained to prevent the recurrence of the condition and to develop effective treatment strategies. This study may be a milestone for studies of this subject. However, this study needs to be confirmed by further studies conducted in a larger series.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Yuan-Yuan Gong ◽  
Hai-Ying Peng

Abstract Background To investigate the correlation between the thickness of epicardial adipose tissue (EAT), C-reactive protein (CRP), interleukin (IL) -6, visfatin, juxtaposed with another zinc finger protein 1 (JAZF1) and type 2 diabetic mellitus (T2DM) macroangiopathy. Methods The study enrolled 82 patients with T2DM with macroangiopathy (the Complication Group), and 85 patients with T2DM (the Diabetes Group) who were admitted to Shandong Provincial Third Hospital from February 2018 to February 2020. In addition, 90 healthy people who underwent physical examination at the same hospital during the same period were enrolled (the Healthy Control Group). Age, gender, height, weight, waist circumference (WC), hip circumference (HC), diabetic course and therapeutic drugs, waist hip ratio (WHR), and body mass index (BMI) were recorded and calculated. Results The baseline characteristics of the three groups were comparable, and the diabetic course of the Complication Group and the Diabetes Group was not significantly different (P > 0.05). The WHR of the Complication Group was higher than that of the Diabetes Group and the Healthy Control Group, with statistical significance (P < 0.05). The FPG, 2hPG, HbA1C, CRP, IL-6, Visfatin, JAZF1, HOMA-IR, EAT thickness, and baPWV of the Complication Group were all higher than those of the Diabetes Group and the Healthy Control Group (P < 0.05, respectively). The JAZF1 and FIns of the Complication Group and Diabetes Group were lower than those of the Healthy Control Group, and JAZF1 of the Complication Group was lower than the Diabetes Group with statistical significance (P<0.05, respectively). Pearson correlation analysis showed that the EAT thickness was positively correlated with CRP, IL-6, visfatin, and JAZF1 (r = 0.387, 0.451, 0.283, 0.301, respectively, all P<0.001). Pearson correlation analysis showed that baPWV was positively correlated with EAT thickness, CRP, IL-6, visfatin, and JAZF1 (r = 0.293, 0.382, 0.473, 0.286, respectively, all P < 0.001). Multivariate stepwise regression analysis showed that FPG, 2hPG, HbA1C, CRP, IL-6, visfatin, JAZF1, and EAT thickness were independent risk factors that affected T2DM macroangiopathy. Conclusions Clinical monitoring and treatment of T2DM macroangiopathy can use CRP, IL-6, Visfatin, JAZF1, and EAT thickness as new targets to delay the progression of the disease. Further research on the relationship between the above factors and the pathogenesis of T2DM macroangiopathy may be helpful provide new treatment strategies.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mingkun Chen ◽  
Li Zhu ◽  
Miao Xue ◽  
Rongrong Zhu ◽  
Liling Jing ◽  
...  

AbstractTo evaluate the feasibility of serum HMGB1, anti-HMGB1 antibodies, and HMGB1/anti-HMGB1 ratio as a diagnosis indicator of initial clinical classification in patients with fever of unknown origin (FUO). Ninety-four patients with classical FUO and ninety healthy controls were enrolled in this study. The subjects’ clinical data and serum were collected. The serum concentration of HMGB1 was detected by a commercial HMGB1 ELISA kit, while the serum concentration of anti-HMGB1 antibodies were detected by an in-house built anti-HMGB1 antibodies ELISA kit and further confirmed by immunoblotting. According to the hospital diagnosis on discharge, ninety-four FUO patients were divided into four groups, Infectious disease subgroup, autoimmune disease subgroup, malignant tumor subgroup, and undetermined subgroup. The concentrations of HMGB1 in the infectious disease subgroup and autoimmune disease subgroup were higher than those in the malignant tumor subgroup, undetermined subgroup, and healthy control group. The concentration of anti-HMGB1 antibodies in autoimmune disease subtype group was higher than those in other subgroups as well as healthy control group. According to the distribution of HMGB1 and anti-HMGB1 in scatter plots of the patients with FUO, we found that the ratio of serum HMGB1/anti-HMGB1 is an ideal clinical indicator for differential diagnosis of different subtypes of FUO. The best cut-off was 0.75, and the sensitivity, specificity, and AUC were 66.67%, 87.32%, and 0.8, respectively. Correlation analysis showed that serum concentration of HMGB1 was moderately correlated with CRP in infectious diseases subgroup, and the serum concentration of anti-HMGB1 antibodies was strongly correlated with erythrocyte sedimentation rate in autoimmune disease subgroup. Our study had showed that serum HMGB1/anti-HMGB1 antibodies ratio can help clinicians identify FUO subtypes, thereby avoiding many unnecessary examinations and tests, and improving the effectiveness of clinical diagnosis and treatment of FUO.


2003 ◽  
Vol 284 (6) ◽  
pp. L1020-L1026 ◽  
Author(s):  
Stephen M. Carlin ◽  
Michael Roth ◽  
Judith L. Black

We investigated the chemotactic action of PDGF and urokinase on human airway smooth muscle (HASM) cells in culture. Cells were put in collagen-coated transwells with 8-μm perforations, incubated for 4 h with test compounds, then fixed, stained, and counted as migrated nuclei by microscopy. Cells from all culture conditions showed some basal migration (migration in the absence of stimuli during the assay), but cells preincubated for 24 h in 10% FBS or 20 ng/ml PDGF showed higher basal migration than cells quiesced in 1% FBS. PDGFBB, PDGFAA, and PDGFABwere all chemotactic when added during the assay. PDGF chemotaxis was blocked by the phosphatidyl 3′-kinase inhibitor LY-294002, the MEK inhibitor U-0126, PGE2, formoterol, pertussis toxin, and the Rho kinase inhibitor Y-27632. Urokinase alone had no stimulatory effect on migration of quiescent cells but caused a dose-dependent potentiation of chemotaxis toward PDGF. Urokinase also potentiated the elevated basal migration of cells pretreated in 10% FBS or PDGF. This potentiating effect of urokinase appears to be novel. We conclude that PDGF and similar cytokines may be important factors in airway remodeling by redistribution of smooth muscle cells during inflammation and that urokinase may be important in potentiating the response.


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