scholarly journals Effect of dermatan sulphate on a C57-mouse model of pulmonary fibrosis

2019 ◽  
Vol 47 (6) ◽  
pp. 2655-2665
Author(s):  
Jianfeng Xu ◽  
Wei Li ◽  
Shufen Xu ◽  
Weiyang Gao ◽  
Zhenyu Yu
Keyword(s):  
Pulmonary Fibrosis ◽  
Mouse Model ◽  
Lung Tissue ◽  
Interstitial Fibrosis ◽  
Group Versus ◽  
Tissue Type ◽  
Control Group ◽  
Prednisolone Acetate ◽  
Sulphate Group ◽  
Dermatan Sulphate

Objective To test the antifibrotic effect of dermatan sulphate in a bleomycin-induced mouse model of pulmonary fibrosis. Methods C57 mice were randomly divided into four experimental groups: saline-treated control group, bleomycin-induced fibrosis group, prednisolone acetate group and dermatan sulphate group. Lungs were assessed using the lung index, and the extent of interstitial fibrosis was graded using histopathological observation of haematoxylin & eosin-stained lung tissue. Lung tissue hydroxyproline levels and blood fibrinogen levels were measured using a hydroxyproline colorimetric kit and the Clauss fibrinogen assay, respectively. Tissue-type plasminogen activator (tPA) was measured using a chromogenic tPA assay kit. Results Lung index values were significantly lower in the dermatan sulphate group versus the fibrosis group. Histopathological analyses revealed that dermatan sulphate treatment ameliorated the increased inflammatory cell infiltration, and attenuated the reduction in interstitial thickening, associated with bleomycin-induced fibrosis. Hydroxyproline and fibrinogen levels were decreased in the dermatan sulphate group versus the fibrosis model group. Dermatan sulphate treatment was associated with increased tPA levels versus controls and the fibrosis group. Conclusions Damage associated with bleomycin-induced pulmonary fibrosis was alleviated by dermatan sulphate.

scholarly journals Protective Effects of Korean Herbal Remedy against Airway Inflammation in an Allergic Asthma by Suppressing Eosinophil Recruitment and Infiltration in Lung

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 6
Author(s):  
Soyon Yoon ◽  
Seokcheon Song ◽  
Jae Woo Shin ◽  
Sini Kang ◽  
Hye Young Kim ◽  
...  
Keyword(s):  
Mouse Model ◽  
Allergic Asthma ◽  
Lung Tissue ◽  
Oral Delivery ◽  
Herbal Remedy ◽  
Periodic Acid ◽  
Lymphoid Cells ◽  
Lung Epithelial Cells ◽  
Eosinophil Infiltration ◽  
Control Group

The increasing prevalence of allergic asthma has become the world’s major health issue. Current treatments for allergic asthma focus on treating symptoms, while permanent cures still remain undiscovered. In this study, we investigated the effect of Korean traditional herbal remedy, Pyunkang-tang (PGT)—composed of six plants—on asthma alleviation in a mouse model. The PGT mixture was orally gavaged to mice (PM group, 20 mg/mouse/day) from 7 days before sensitization with ovalbumin (OVA) (day −7). On day 0 and day 14, mice from OVA-control (n = 9) and PM group (n = 8) were sensitized with OVA and alum through intraperitoneal injection. On days 18~20, OVA was challenged to mice through nasal injection and sacrificed next day. Cell profile in lung tissue was analyzed by flow cytometry and RT-qPCR analysis, and the number of eosinophils and expression of siglec-F were significantly reduced in the PM group. Lung tissue was examined with hematoxylin and eosin (H&E) and Alcian blue/periodic acid–Schiff (AB-PAS) staining. Noticeably reduced eosinophil infiltration around bronchioles was displayed in the PM group compared to the OVA-control group. Furthermore, PGT-treated mice showed a significant reduction in IL-13 and a mild reduction in IL-5 in lungs. A decreasing tendency of IL-5/13 (+) CD4+ T cells and IL-13(+) innate lymphoid cells (ILCs) and a significant reduction in IL5(+) ILCs were also observed. When treating PGT on murine lung epithelial cells stimulated by papain, there was a significant reduction in IL-33 mRNA expression levels. Taken together, oral delivery of PGT successfully alleviated asthmatic responses provoked by OVA in a mouse model and could lead to novel therapies for allergic asthma.

scholarly journals Astragaloside IV Synergizing with Ferulic Acid Ameliorates Pulmonary Fibrosis by TGF-β1/Smad3 Signaling

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Jiahuan Tong ◽  
Zhisong Wu ◽  
Yuchen Wang ◽  
Qingxun Hao ◽  
Haoge Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Fibrosis ◽  
Ferulic Acid ◽  
Lung Tissue ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Sham Operation ◽  
Astragaloside Iv ◽  
Group A ◽  
Tgf Β1

Objective. The study aims to research the interventional effect and mechanism of astragaloside IV (Ast) synergizing with ferulic acid (FA) on idiopathic pulmonary fibrosis (IPF) induced by bleomycin in mice. Methods. The mice were randomly divided into seven groups with 10 mice in each group, namely, a sham operation group, a model group, a miRNA-29b (miR-29) group, a miR-29b negative control group (NC group), a FA group, an Ast group, and a combination group. A mouse model of pulmonary fibrosis was established by intratracheal instillation of bleomycin. Samples were collected after 28 days of continuous administration. Hematoxylin and eosin (HE) and Masson staining were used to observe pathological changes in the lung tissue, and the degree of fibrosis was evaluated using the hydroxyproline content. Changes in transforming growth factor-β1 (TGF-β1) and Smad3 in the lung were observed using immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) in the serum. PCR was used to detect the expression of the miR-29b, TGF-β1, Smad3, and nuclear factor E2-related factor 2 (Nrf2) genes. Western blotting was used to detect the content of the TGF-β/Smad3 protein. Results. Ferulic acid combined with astragaloside IV reduced the degree of pulmonary fibrosis and the synthesis of hydroxyproline in lung tissue. The combination of the two also regulated the oxidative stress response ， TGF-β1/Smad3 pathway and miR-29b in lung tissue. Conclusion. Astragaloside IV combined with ferulic acid regulated the oxidative stress of lung tissues and TGF-β1/Smad3 signaling through miR-29b, thereby reducing the degree of pulmonary fibrosis. This provides a reference direction for the clinical treatment of IPF patients.

scholarly journals Curcumin alone and in combination with augmentin protects against pulmonaryinflammation and acute lung injury generated during Klebsiella pneumoniae B5055-induced lung infection in BALB/c mice

2010 ◽  
Vol 59 (4) ◽  
pp. 429-437 ◽  
Author(s):  
Shruti Bansal ◽  
Sanjay Chhibber
Keyword(s):  
Klebsiella Pneumoniae ◽  
Mouse Model ◽  
Lung Tissue ◽  
Inflammatory Mediators ◽  
Bacterial Load ◽  
Neutrophil Infiltration ◽  
Lung Infection ◽  
Control Group ◽  
Intranasal Route ◽  
Anti Inflammatory

Acute lung injuries due to acute lung infections remain a major cause ofmortality. Thus a combination of an antibiotic and a compound with immunomodulatoryand anti-inflammatory activities can help to overcome acute lung infection-inducedinjuries. Curcumin derived from the rhizome of turmeric has been used fordecades and it exhibits anti-inflammatory, anti-carcinogenic, immunomodulatoryproperties by downregulation of various inflammatory mediators. Keeping theseproperties in mind, we investigated the anti-inflammatory properties of curcuminin a mouse model of acute inflammation by introducing Klebsiella pneumoniae B5055 into BALB/c mice via the intranasal route. Intranasal instillationof bacteria in this mouse model of acute pneumonia-induced inflammation resultedin a significant increase in neutrophil infiltration in the lungs along withincreased production of various inflammatory mediators [i.e. malondialdehyde (MDA),myeloperoxidase (MPO), nitric oxide (NO), tumour necrosisfactor (TNF)-α] in the lung tissue. The animalsthat received curcumin alone orally or in combination with augmentin, 15 daysprior to bacterial instillation into the lungs via the intranasal route, showeda significant (P <0.05) decrease in neutrophil influxinto the lungs and a significant (P <0.05) decreasein the production of MDA, NO, MPO activity and TNF-α levels.Augmentin treatment alone did not decrease the MDA, MPO, NO and TNF-α levels significantly (P >0.05) as compared tothe control group. We therefore conclude that curcumin ameliorates lung inflammationinduced by K. pneumoniae B5055 without significantly (P <0.05) decreasing the bacterial load in the lung tissue whereasaugmentin takes care of bacterial proliferation. Hence, curcumin can be usedas an adjunct therapy along with antibiotics as an anti-inflammatory or animmunomodulatory agent in the case of acute lung infection.

scholarly journals Dynamic Observation of Autophagy and Transcriptome Profiles in a Mouse Model of Bleomycin-Induced Pulmonary Fibrosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Yani Wang ◽  
Siqi Hu ◽  
Lisha Shen ◽  
Song Liu ◽  
Linyan Wan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pulmonary Fibrosis ◽  
Mouse Model ◽  
Muscle Contraction ◽  
Signaling Pathway ◽  
Lung Tissue ◽  
Critical Role ◽  
Mouse Lung ◽  
Mouse Lung Tissue

Pulmonary fibrosis is a group of progressive, fibrotic, and fatal lung diseases, and the role of autophagy in pulmonary fibrosis is controversial. In the current research, we dynamically observed a bleomycin-induced pulmonary fibrosis mouse model after 3, 7, 14, 21, and 28 days and investigated the expression of autophagy markers. We found that autophagy markers were not significantly changed on the indicated days in the mouse lung tissue. Then, RNA-Seq was used to analyze the gene expression and associated functions and pathways in fibrotic lung tissue on different days post-bleomycin. In addition, short time series expression miner (STEM) analysis was performed to explore the temporal post-bleomycin gene expression. Through STEM, continually up- or downregulated profiles did not demonstrate the critical role of autophagy in the development of fibrosis. Furthermore, gene ontology (GO) annotations showed that continually upregulated profiles were mainly related to fibrosis synthesis, extracellular space, and inflammation, while enriched pathways were mainly related to the PI3K-Akt signaling pathway, ECM–receptor interactions, and focal adhesion signaling pathway. For continually downregulated profiles, GO annotations mainly involved sarcomere organization, muscle contraction, and muscle fiber development. The enriched KEGG signaling pathways were the cAMP signaling pathway, cGMP-PKG signaling pathway, calcium signaling pathway, and cardiac muscle contraction. Moreover, we analyzed autophagy-related genes’ expression in specific cells from a publicly available database of three human and one animal study of pulmonary fibrosis using single-cell sequencing technology. All results consistently demonstrated no critical role of autophagy in the pathogenesis of pulmonary fibrosis. In summary, autophagy may not critically and consistently change during the development of pulmonary fibrosis at different stages post-bleomycin in a mouse model. These continually up- or downregulated profiles, including gene profiles, and the corresponding functions and pathways may provide mechanistic insights into IPF therapy.

Probable Roles of Coagulation Cascade and Fibrinolysis System in the Development of Allergic Rhinitis

2018 ◽  
Vol 33 (2) ◽  
pp. 137-144 ◽  
Author(s):  
Seung-No Hong ◽  
Yu-Lian Zhang ◽  
Chae-Seo Rhee ◽  
Dong-Young Kim
Keyword(s):  
Allergic Rhinitis ◽  
Mouse Model ◽  
Plasminogen Activator ◽  
Ar Model ◽  
Coagulation Cascade ◽  
Tissue Type ◽  
Coagulation System ◽  
Control Group ◽  
Fibrin Deposition ◽  
Type Plasminogen Activator

Background Dysregulation of the coagulation cascade and fibrinolysis system may play an etiologic role in many diseases. Allergic diseases such as bronchial asthma, atopic dermatitis, and conjunctivitis are also associated with fibrin accumulation caused by a change in hemostasis. However, only a few studies have dealt with the relationship between allergic rhinitis (AR) and the coagulation system. Objective We investigated the difference of coagulation and fibrinolysis cascade components between an AR mouse model and a control mice. Methods BALB/c mice were sensitized and challenged with ovalbumin. Multiple parameters of coagulation cascade and fibrinolysis system such as factors II, V, VII, X, and XIII; tissue-type plasminogen activator; urokinase-type plasminogen activator (u-PA); plasminogen activator inhibitor-1 (PAI-1); and fibrin were compared between the AR model group and the control group. Results The symptom scores and eosinophil counts were higher in the AR group than in the control group ( P < .01). The mRNA expression level of u-PA ( P = .040) was significantly lower, and the expression levels of factor II ( P = .038) and factor X ( P = .036) were significantly higher, in the AR group. Immunohistochemical staining revealed that most of the fibrinolysis system and coagulation cascade components were localized to the epithelium, endothelium, and submucosal glands of the nasal mucosa. u-PA was downregulated in the AR group, whereas fibrin deposition was more prominent in the AR group than in the control group. Conclusion In AR, particular components of the coagulation cascade were increased and fibrinolysis system was decreased compared to normal control. This difference may be associated with the fibrin deposition in the mucosa of AR mouse model.

scholarly journals Effect of Total Flavonoids of Oxytropis falcata Bunge on the Expression of p-JAK1-and p-STAT1-Related Proteins in Idiopathic Pulmonary Fibrosis

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Yan-jun Wang ◽  
Yang Li ◽  
Xue-lin Wang ◽  
Xin-ze Li ◽  
Yan-wen Chen ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Tissue ◽  
Positive Control ◽  
Prednisolone Acetate ◽  
High Dose ◽  
Total Flavonoids ◽  
Transmission Electron ◽  
Kg Medium ◽  
Related Proteins

Objective. The study aimed to explore the effect of total flavonoids of Oxytropis falcata Bunge (FOFB) on the expression of p-JAK1/p-STAT1 and SOCS3 proteins in idiopathic pulmonary fibrosis (IPF). Methods. Rats model with IPF was established by one-off intratracheal injection of bleomycin (BLM, 5 mg/kg). After 14 days, the same volume of low dose (100 mg/kg), medium dose (200 mg/kg), and high dose (400 mg/kg) of FOFB and prednisolone acetate (20 mg/kg) as positive control drugs, as well as normal saline, were orally administered to rats once a day for 28 consecutive days. Subsequently, the degree of fibrosis and alveolitis in rat lung tissue was observed, respectively, by HE and Masson staining. Further more, observing the ultrastructure of lung tissue by transmission electron microscopy (TEM), the detection of JAK/STAT pathway related indicators including p-JAK1, p-STAT1, and SOCS3 with immunohistochemistry and SOCS3 with real-time PCR (RT-PCR) was performed. Results. Compared with the BLM group, the degree of alveolitis and fibrosis improved significantly, and the expression of p-JAK1 and p-STAT1 decreased; conversely, the expression of SOCS3 increased in the treatment group. Conclusion. IPF causes high expression of p-JAK1 and p-STAT1 and low expression of SOCS3. FOFB can play a role in the treatment of IPF via upregulating SOCS3 and downregulating p-JAK1 and p-STAT1.

scholarly journals Targeted Inhibition of ROCK Specifically in the Polarization Interstitial Macrophages Suppresses Pulmonary Fibrosis

2021 ◽  
Author(s):  
Qingfang Li ◽  
Yuan Cheng ◽  
Zhenfei Bi ◽  
Xuelei Ma ◽  
Yuquan Wei ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Tissue ◽  
Control Group ◽  
High Dose ◽  
Intragastric Administration ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Mice Model ◽  
Tissue Repair And Regeneration ◽  
Radiation Induced

Abstract Background Pulmonary fibrosis (PF) is a kind of progressive interstitial lung disease with no effective therapy. Rho/ROCK pathway has been confirmed to be activated in the process of PF in bleomycin-induced mice model in previous studies, which is involved in cell proliferation, tissue repair and regeneration. Bleomycin-induced and radiation-induced pulmonary fibrosis mice models were used to explore the effects and mechanism of WXWHO265, a novel unselected ROCK inhibitor, in PF.Methods The bleomycin-induced mice models were constructed by intratracheal instillation. The radiation-induced mice model were established by bilateral thoracic irradiation. Intragastric administration was applied to the WXWHO265 treated groups one day after model established. Flow cytometry, qRT-PCR, HE staining, Masson staining, and immunohistochemistry (IHC) analysis were used for further investigation.ResultsIn both types of PF models, the fibrosis in the lung was severe and became worse as time progressed. The status of mice in WXWHO265 treated groups was better than control group (saline treated group). The proportion of M2 macrophages in the lung tissue of bleomycin-induced group significantly increased compared to control group. The proportion of M2 macrophage of day 28 was higher than day 14 and day 7 in both PF models. The proportions of M2 macrophage in WXWHO265 high dose group(25mg/kg) and control group were statistically different (p<0.05). The p-STAT3 in lung tissue was significantly decreased in the day 28 in PF models. In vitro macrophages polarization experiment, the macrophages transformed into M2 macrophages by IL-4 stimulating. The proportion of M2 macrophages decreased after treated with WXWHO265. ConclusionsInhibiting ROCK could significant ameliorate PF in mice model by regulating the polarization of interstitial macrophages. Furthermore, the results showed that ROCK regulated the polarization of M2 macrophages by mediating the phosphorylation of STAT3, which might be a potential target in treating PF.

Nickel oxide nanoparticles induced pulmonary fibrosis via TGF-β1 activation in rats

2016 ◽  
Vol 36 (8) ◽  
pp. 802-812 ◽  
Author(s):  
XH Chang ◽  
A Zhu ◽  
FF Liu ◽  
LY Zou ◽  
L Su ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Nickel Oxide ◽  
Lung Tissue ◽  
Messenger Rna ◽  
Transforming Growth Factor ◽  
Quantitative Polymerase Chain Reaction ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Tgf Β1

Nano nickel oxide (NiO), widely used in industry, has recently been discovered to have pulmonary toxicity. However, no subchronic exposure studies about nano NiO-induced pulmonary fibrosis have been reported. The objective of this study was to investigate pulmonary fibrosis induced by nano NiO and its potential mechanism in rats. Male Wistar rats ( n = 40, 200–240 g) were randomized into control group, nano NiO groups (0.015, 0.06, and 0.24 mg/kg), and micro NiO group (0.024 mg/kg). All rats were killed to collect lung tissue after intratracheal instillation of NiO particles twice a week for 6 weeks. To identify pulmonary fibrosis, Masson trichrome staining, hydroxyproline content, and collagen protein expression were performed. The results showed widespread lung fibrotic injury in histological examination and increased content of hydroxyproline, collagen types I and III in rat lung tissue exposed to nano NiO. To explore the potential pulmonary fibrosis mechanism, transforming growth factor beta 1 (TGF- β1) content was measured by enzyme-linked immunosorbent assay, and the messenger RNA expression of key indicators was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The TGF- β1 content was increased in nano NiO exposure groups, as well as the upregulated gene expression of TGF- β1, Smad2, Smad4, matrix metalloproteinase, and tissue inhibitor of metalloproteinase. The findings indicated that nano NiO could induce pulmonary fibrosis, which may be related to TGF- β1 activation.

scholarly journals Quantification of Early Diffuse Myocardial Fibrosis Through 7.0 T Cardiovascular Magnetic Resonance T1 Mapping in a Type 1 Diabetic Mellitus Mouse Model

2021 ◽  
Author(s):  
Hongkai Zhang ◽  
Chun-Yan Shi ◽  
Lin Yang ◽  
Nan Zhang ◽  
Guo-qi Li ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Mouse Model ◽  
T1 Mapping ◽  
Volume Fraction ◽  
Interstitial Fibrosis ◽  
Early Stage ◽  
Extracellular Volume ◽  
Control Group ◽  
Post Contrast

Abstract Background Diffuse myocardial interstitial fibrosis (DMIF) is a key factor for heart failure (HF) in diabetic cardiomyopathy. This study examined the accuracy of the qualitative and quantitative evaluation of early DMIF in a type 1 diabetes mellitus (T1DM) mouse model through 7.0 T cardiac magnetic resonance imaging-based T1 mapping.Methods Eight-week-old C57Bl/6J male mice were randomly divided into control (n = 20) and T1DM (n = 30, induced by a low dose streptozotocin dose of 60 mg/kg) groups. The progression of DMIF was examined every 4 weeks until 24 weeks after successful establishment of the model. Cardiac functional and morphological parameters were evaluated through echocardiography by using a high-resolution ultrasound cardiovascular system. A 7.0 T CMR scan was performed using the pre- and post-contrast GRE Look–Locker inversion recovery T1 mapping sequence. The extracellular volume fraction (ECV) was calculated from CMR and hematocrit data. Sirius Red staining was simultaneously performed in each group to detect DMIF and calculate the collagen volume fraction (CVF). Differences in ECV and CVF values between two groups were analyzed using one-way analysis of variance. The correlation between ECV and CVF values was assessed using the Pearson test.Results Six mice were included every 4 weeks in the control and T1DM groups for statistical analysis. Compared with the control group, a progressive decrease in FS, EF, and E/A ratio was observed in the T1DM group. In the T1DM group, both ECV and CVF values were gradually increased during diabetes progression. A marked increase in ECV and CVF values was observed at 12 weeks in the T1DM group than in the control group (ECV: 32.5% ± 1.6% vs 28.1% ± 1.8%, P = 0.002; CVF: 6.9% ± 1.8% vs 3.3% ± 1.1%, P < 0.01). ECV values showed a strong correlation with CVF in the T1DM group (r = 0.856, P < 0.001).Conclusion ECV is a reliable and feasible imaging marker that can be used to quantitatively assess dynamic DMIF changes in T1DM mice. In addition, ECV could accurately detect DMIF in the early stage and thus can be used as an imaging tool for early intervention in T1DM mice in the future.

Deep Vein Thrombosis and Fibrinolysis

1991 ◽  
Vol 66 (04) ◽  
pp. 426-429 ◽  
Author(s):  
Marcel Levi ◽  
Anthonie W A Lensing ◽  
Harry R Büller ◽  
Paolo Prandoni ◽  
Gerard Dooijewaard ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Controlled Study ◽  
First Episode ◽  
Control Group ◽  
Vein Thrombosis ◽  
Type Plasminogen Activator ◽  
Deep Vein

SummaryIn the present study 57 consecutive patients with a first episode of venographically proven deep vein thrombosis were investigated to evaluate the release of tissue-type plasminogen activator (t-PA) and of urokinase-type plasminogen activator (u-PA) in response to DDAVP stimulation as well as the resting plasminogen activator inhibitor (PAI) concentration, comparing this to the results obtained in 66 similar patients with a clinical suspicion of thrombosis but with a normal venogram. All assays were performed without knowledge of the patient's status.Four patients in the deep vein thrombosis-group (7%) had an absent u-PA antigen response upon DDAVP infusion, while a normal response was observed in all control subjects. Patients and controls showed similar increases in t-PA antigen level upon DDAVP. High resting PAI antigen levels were encountered in 5 patients in the deep vein thrombosis-group (9%) and in 6 subjects in the control group (9%).The results from this controlled study indicate that a defective release of u-PA may occur in patients with deep vein thrombosis and may have pathogenetic significance. Furthermore it is concluded that elevation of PAI levels cannot be considered as a specific risk factor for venous thrombosis.

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