scholarly journals Bufei Decoction Alleviated Bleomycin-Induced Idiopathic Pulmonary Fibrosis in Mice by Anti-Inflammation

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Shanjun Yang ◽  
Wenwen Cui ◽  
Mingye Wang ◽  
Luming Xing ◽  
Yue Wang ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Morphological Changes ◽  
Therapeutic Option ◽  
Signal Transduction Pathway ◽  
Inflammatory Cells ◽  
Control Group ◽  
Therapeutic Effects ◽  
Group Model ◽  
Anti Inflammation

Objective. This study aimed to investigate the mechanistic action and therapeutic effects of Bufei decoction on idiopathic pulmonary fibrosis (IPF) after inhalation of bleomycin. Methods. Pulmonary fibrosis model in mice was prepared by atomization inhalation of bleomycin. Then, the mice were randomly divided into five groups (control group, model group, positive group, and treatment group) and administrated the drugs for 4 weeks. H&E and Masson’s staining of lung tissues were used to observe the morphological changes and deposition of fibers, and the degree of fibrosis was evaluated by hydroxyproline content. The expression and activation of NF-κB were determined by western blotting and immunohistochemistry. The infiltration of macrophages was detected by immunostaining of CD45 and F4/80 in lung tissues. Results. In mouse IPF, Bufei decoction alleviated the pathological changes and the deposition of fibrosis by decreasing the content of hydroxyproline of lung tissues. The antipulmonary fibrosis might rely on the effects of preventing the infiltration of inflammatory cells and inhibiting the expression and activation of NF-κB in lung tissue. Conclusion. Bufei decoction improved the process of pulmonary fibrosis by regulating the activation and expression of the NF-κB signal transduction pathway, which provided a therapeutic option for IPF patients.

scholarly journals microRNA-186 in extracellular vesicles from bone marrow mesenchymal stem cells alleviates idiopathic pulmonary fibrosis via interaction with SOX4 and DKK1

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Zhou ◽  
Yang Lin ◽  
Xiuhua Kang ◽  
Zhicheng Liu ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Extracellular Vesicles ◽  
Luciferase Assay ◽  
Therapeutic Effects ◽  
Loss Of Function ◽  
Fibroblast Activation ◽  
Promising Therapeutic Approach

Abstract Background Previous reports have identified that human bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) with their cargo microRNAs (miRNAs) are a promising therapeutic approach for the treatment of idiopathic pulmonary fibrosis (IPF). Therefore, we explored whether delivery of microRNA-186 (miR-186), a downregulated miRNA in IPF, by BMSC EVs could interfere with the progression of IPF in a murine model. Methods In a co-culture system, we assessed whether BMSC-EVs modulated the activation of fibroblasts. We established a mouse model of PF to evaluate the in vivo therapeutic effects of BMSC-EVs and determined miR-186 expression in BMSC-EVs by polymerase chain reaction. Using a loss-of-function approach, we examined how miR-186 delivered by BMSC-EVs affected fibroblasts. The putative relationship between miR-186 and SRY-related HMG box transcription factor 4 (SOX4) was tested using luciferase assay. Next, we investigated whether EV-miR-186 affected fibroblast activation and PF by targeting SOX4 and its downstream gene, Dickkopf-1 (DKK1). Results BMSC-EVs suppressed lung fibroblast activation and delayed IPF progression in mice. miR-186 was downregulated in IPF but enriched in the BMSC-EVs. miR-186 delivered by BMSC-EVs could suppress fibroblast activation. Furthermore, miR-186 reduced the expression of SOX4, a target gene of miR-186, and hence suppressed the expression of DKK1. Finally, EV-delivered miR-186 impaired fibroblast activation and alleviated PF via downregulation of SOX4 and DKK1. Conclusion In conclusion, miR-186 delivered by BMSC-EVs suppressed SOX4 and DKK1 expression, thereby blocking fibroblast activation and ameliorating IPF, thus presenting a novel therapeutic target for IPF.

scholarly journals Meta-Analysis of Clinical Efficacy and Safety of Ligustrazine in the Treatment of Idiopathic Pulmonary Fibrosis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Xiaozheng Wu ◽  
Wen Li ◽  
Zhenliang Luo ◽  
Yunzhi Chen
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Clinical Efficacy ◽  
Adverse Reactions ◽  
Clinical Symptoms ◽  
Gas Analysis ◽  
Control Group ◽  
Efficacy And Safety ◽  
Arterial Blood Gas ◽  
Arterial Blood

Objective. To systematically review the efficacy and safety of Ligustrazine in the treatment of idiopathic pulmonary fibrosis (IPF). Methods. The electronic literature databases (PubMed, EMbase, CNKI, WanFang database, and VIP) were retrieved through a computer to find out the randomized controlled trials (RCT) of Ligustrazine in the treatment of IPF according to the inclusion/exclusion criteria screening test. Cochrane’s bias risk table was also used to evaluate the quality of the study and to extract effective data. RevMan 5.3 was used for statistical analysis. Results. A total of 7 RCTs (a total of 366 patients, including 196 in experimental and 170 in control group). Compared with the control group, Ligustrazine could improve the clinical symptoms ([OR] = 2.20, 95% CI [1.40, 3.46], P = 0.0006 ), lung function (VC % [MD] = 3.92, 95% CI [0.68, 7.17], P = 0.02 ), (TLC% [MD] = 4.94, 95% CI [0.37, 9.52], P = 0.03 ), the pulmonary diffusion function (DLCO % [MD] = 9.12, 95% CI [5.70, 12.55], P < 0.00001 ), and arterial blood gas analysis (PaO2 [MD] = 7.11, 95% CI [1.96, 12.25], P = 0.007 ) (PaCO2 [MD] = −2.42, 95% CI [−4.36, −0.49], P = 0.01 ) of IPF patients, respectively. However, FEV1/FVC % ([MD] = 9.37, 95% CI [−1.23, 19.97], P = 0.08 ) and adverse reactions ([MD] = 0.35, 95% CI [0.02, 5.36], P = 0.45 ) were not significantly improved. Conclusion. Ligustrazine has certain clinical efficacy in the treatment of IPF, but the safety of applying it and the adverse reactions need to be further analyzed and determined. It can be considered as a new alternative and complementary medicine to be promoted and recommended for use in medical units in various countries in the world and it solved the difficult problem of conventional drug treatment of IPF; therefore, more research strength can be put in the treatment of the pathological mechanism of IPF for further exploration. The study was registered under registration number CRD42020193626.

scholarly journals Pathogenic and clinical trial of N-acetylcysteine (Fluimucil) in idiopathic pulmonary fibrosis

2005 ◽  
pp. 34-41
Author(s):  
E. N. Popova ◽  
B. M. Kornev ◽  
K. U. Reznikova ◽  
O. V. Kondarova
Keyword(s):  
Antioxidant Activity ◽  
Free Radical ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Immunosuppressive Drugs ◽  
Open Lung Biopsy ◽  
Control Group ◽  
Term Administration ◽  
The Mean ◽  
Plasma Antioxidant

The aim of this study was to investigate free radical and lipid disorders in idiopathic pulmonary fibrosis (IPF), to assess clinical efficacy of Fluimucil and to substantiate its administration in different stages of the disease. We observed 127 IPF patients, of them 59 were treated typically with prednisolone, colchicines, or azathioprin, 68 ones received immunosuppressors and Fluimucil. The diagnosis of IPF was verified morphologically in open lung biopsy samples. The patients’ age was 25 to 74 yrs, the mean age, 46.7 ± 9.8 yrs. A control group included 20 healthy donors, the mean age, 41.2 ± 1.2 yrs. N-acetylcysteine (Fluimucil, Zambon group) was administered initially IV 1800 mg a day for 14 days, then orally 1 800 mg a day for a month, then 600 mg a day for 3 months. Clinical and free radical conditions were monitored before the treatment and 3, 6 and 12 months starting the therapy. Fluimucil improved thrombocyte antioxidant activity and plasma antioxidant activity, reduced CT signs of IPF, provided a stable growth in FEV1 and FVC (by 10 % and 12 % respectively) and DLco. Fluimucil was well-tolerated, adverse effects (nausea, stomach ache) were noted in 7 patients (10.2 %). Thus, the results confirmed antioxidant efficacy of Fluimucil in IPF. The long-term administration of Fluimucil combined with the immunosuppressive drugs in IPF patients was safe and reasonable as this inhibited progression of the disease.

Hypoxia during pregnancy in rats leads to early morphological changes of atherosclerosis in adult offspring

2009 ◽  
Vol 296 (5) ◽  
pp. H1321-H1328 ◽  
Author(s):  
Zhenhua Wang ◽  
Ziyang Huang ◽  
Guorong Lu ◽  
Ling Lin ◽  
Markus Ferrari
Keyword(s):  
Morphometric Analysis ◽  
Time Course ◽  
Morphological Changes ◽  
Adult Life ◽  
Inflammatory Cells ◽  
Prenatal Hypoxia ◽  
Control Group ◽  
Adult Offspring ◽  
Sprague Dawley ◽  
Maternal Hypoxia

Exposure to an adverse intrauterine environment increases the risk of cardiovascular disease later in adult life. However, the time course relationship between prenatal hypoxia and the onset of atherosclerosis in offspring remains unknown. The purpose of this study is to evaluate the role of reduced fetal oxygen supply on early development of atherogenesis in the adult offspring and further assess its susceptibility to sex-, hyperlipidemia-, and postnatal hypoxemia-related differences. Based on a 4 × 2 full factorial design consisting of four factors of maternal hypoxia, sex, hyperlipidemia, and postnatal hypoxemia, characteristics of growth were determined, and histopathological observation and morphometric analysis of the thoracic aortas were performed in Sprague-Dawley rat offspring. Intrauterine growth restriction, altered body shape at birth, and accelerated postnatal weight gain occurred in the maternal hypoxia group but did not occur in the control group. In 16-mo-old maternal hypoxia offspring, the thoracic aortas exhibited lesions similar to early events in atherosclerosis that involved impaired endothelial cells, thickening and fibration of intimas, infiltration of inflammatory cells to the subendothelial space, and migration and proliferation of vascular smooth muscle cells to the intima. In contrast, no detectable pathological changes were observed in the offspring without maternal hypoxia exposure. Morphometric analysis further demonstrated that prenatal hypoxia caused a significant thickening of intima ( P < 0.001) with a main effect of 5.5 μm, an approximately twofold increase compared with controls. In addition, there was a positive additive relationship between prenatal hypoxia and hyperlipidemia on the intimal thickness ( P < 0.05). There were no other main effects or interaction among these four factors. In summary, our results indicate that maternal hypoxia during pregnancy leads to early pathological appearances of atherogenesis in adult offspring. This effect was enhanced with hyperlipemia but was unaffected by postnatal hypoxia or sex.

scholarly journals Role of the Hippo signaling pathway in safflower yellow pigment treatment of paraquat-induced pulmonary fibrosis

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052090542
Author(s):  
Hai Li ◽  
Baotian Kan ◽  
Lingli Song ◽  
Yufa Liu ◽  
Xiangdong Jian
Keyword(s):  
Growth Factor ◽  
Pulmonary Fibrosis ◽  
Quantitative Polymerase Chain Reaction ◽  
Tissue Growth ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Therapeutic Effects ◽  
Hippo Signaling ◽  
Exposure Group ◽  
Tgf Β1

Objective To elucidate the molecular mechanisms by which safflower yellow (SY) mediates therapeutic effects in rats with paraquat intoxication-induced pulmonary fibrosis. Methods Rats received combinations of paraquat, SY, and SB431542, a transforming growth factor (TGF)-β1 receptor antagonist. Survival over 28 days was assessed by Kaplan–Meier analysis. Rat tissue and serum samples were assessed by hematoxylin and eosin staining, Masson’s Trichrome staining, immunoblotting, quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and transmission electron microscopy. Results Survival rates were higher in SY and SB431542 groups (treatment and paraquat) than in the exposure group (paraquat alone). In the exposure group, serum TGF-β1 levels increased between days 3 and 14; mammalian STE20-like (MST) levels increased between days 3 and 7; TGF-β1 and Smad3 levels increased between days 3 and 14; and Yap and connective tissue growth factor levels increased between days 3 and 28. TGF-β1 levels were lower in SY and SB431542 groups than in the exposure group. Pathology scores were higher in exposure, SY, and SB431542 groups than in the control group throughout the experiment. Conclusions In rats with paraquat intoxication-induced pulmonary fibrosis, Hippo signaling could be activated by the MST-Yap pathway; SY and SB431542 could alleviate pulmonary fibrosis via Hippo signaling.

scholarly journals Hataedock Treatment Has Preventive Therapeutic Effects in Atopic Dermatitis-Induced NC/Nga Mice under High-Fat Diet Conditions

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Ho-Yeol Cha ◽  
Sang-hyun Ahn ◽  
Jin-Hong Cheon ◽  
In-Sik Park ◽  
Jin-Tack Kim ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Morphological Changes ◽  
Skin Lesions ◽  
Control Group ◽  
Therapeutic Effects ◽  
High Fat ◽  
Coptidis Rhizoma ◽  
Inflammatory Regulation ◽  
Th2 Differentiation ◽  
Old Mice

This study investigated the preventive therapeutic effects of Hataedock (HTD) treatment on inflammatory regulation and skin protection in AD-induced NC/Nga mice under high-fat diet conditions. Before inducing AD, the extract ofCoptidis RhizomaandGlycyrrhiza uralensiswas administered orally to the 3-week-old mice. After that, AD-like skin lesions were induced by applying DNFB. All groups except the control group were fed a high-fat diet freely. We identified the effects of HTD on morphological changes, cytokine release and the induction of apoptosis through histochemistry, immunohistochemistry, and TUNEL assay. HTD downregulated the levels of IL-4 and PKC but increased the levels of LXR. HTD also suppressed the mast cell degranulation and release of MMP-9, Substance P. The levels of TNF-α, p-IκB, iNOS, and COX-2 were also decreased. The upregulation of inflammatory cell’s apoptosis is confirmed by our results as increase of apoptotic body and cleaved caspase-3 and decrease of Bcl-2. HTD also reduced edema, angiogenesis, and skin lesion inflammation. Our results indicate HTD suppresses various inflammatory response on AD-induced mice with obesity through the regulation of Th2 differentiation and the protection of lipid barrier. Therefore, HTD could be used as an alternative and preventive therapeutic approach in the management of AD.

Interferon-γ-1b: Therapeutic Option in Advanced Idiopathic Pulmonary Fibrosis?

Respiration ◽  
2004 ◽  
Vol 71 (6) ◽  
pp. 656-657 ◽  
Author(s):  
Claus Kroegel ◽  
Bettina Mock ◽  
Ulf Hengst ◽  
Angelika Reissig
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Therapeutic Option ◽  
Interferon Γ

scholarly journals Laryngopharyngeal pH Monitoring in Patients With Idiopathic Pulmonary Fibrosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yiliang Su ◽  
Li Shen ◽  
Fen Zhang ◽  
Xing Jiang ◽  
Xiaofeng Jin ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Supine Position ◽  
Ph Value ◽  
Laryngopharyngeal Reflux ◽  
Ph Monitoring ◽  
Upright Position ◽  
Index Score ◽  
Control Group ◽  
Healthy Individuals

Background: Patients with idiopathic pulmonary fibrosis (IPF) often have irritating persistent dry cough. Possible correlations between dry cough and laryngopharyngeal reflux (LPR) remain unclear.Methods: 44 patients with IPF and 30 healthy individuals underwent 24 h laryngopharyngeal pH monitoring. Ryan index score was calculated. Patients’ demographic and clinical data were collected.Results: 44 patients with IPF and 30 healthy individuals were included. The proportions of men and smokers were significantly higher in IPF group than control group (All p &lt; 0.01). The average laryngopharyngeal pH value for 24 h was similar in the IPF (7.11 ± 0.08) group and control group (7.09 ± 0.06). According to the percentage duration of pH &lt; 6.5, pH6.5–7.5, and pH &gt; 7.5 in the overall measure duration, the patients were classified into three pH groups. In entire pH monitoring duration, the proportion of pH &gt; 7.5 group in IPF patients was higher than control group; at upright position, the proportion of pH &gt; 7.5 group in IPF patients was higher than control group; at supine position, the proportion of pH &lt; 6.5 group in IPF patients was higher than control group (All p &lt; 0.01). Seven patients had Ryan index score&gt;9.41 at upright position. All patients had Ryan index score&lt;6.79 at supine position. Four patients showed significantly higher and one patient had significantly lower average pH at coughing than the overall average pH (All p &lt; 0.05).Conclusions: Patients with IPF may have LPR. Basic and acidic LPR may likely occur at upright and supine position, respectively. Ryan index may not accurately reflect LPR in patients with IPF.

scholarly journals [Nintedanib for the treatment of idiopathic pulmonary fibrosis in Italy]

2017 ◽  
Vol 18 (1S) ◽  
Author(s):  
Andrea Belisari ◽  
Daria Bettoni ◽  
Paolo Angelo Cortesi ◽  
Lucia Sara D'Angiolella ◽  
Lorenzo Giovanni Mantovani ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Therapeutic Option ◽  
Real Life ◽  
Pharmacoeconomic Evaluation ◽  
Primary Study ◽  
Base Case ◽  
Health States ◽  
Life Years ◽  
Combining Data

To date, there are few therapeutic answers for Idiopathic pulmonary fibrosis (IPF) and only two pharmacological treatments have a marketing authorization for this disease. Recently nintedanib (Ofev®) has been authorized as a new therapeutic option and its economic profile has been evaluated by international Health Technology Assessment (HTA) bodies. IPF has important implications for everyday life of patients and their carers, negatively influencing their quality of life and bringing heavy economic burden to the NHS and to the entire society. It is, therefore important to consider these aspects for the Italian environment and to perform a pharmacoeconomic evaluation to define the efficiency of nintedanib in IPF by means of a Cost-Utility Analysis (CUA). As IPF is a chronic and progressive disease, a lifetime Markov model has been therefore developed with health states describing the patient’s condition as a combination of lung function and exacerbation history. The cohort entered in the model at different Forced Vital Capacity (FVC%) predicted health states, without exacerbation. The Clinical data used to perform this CUA were derived from clinical trials and the relative efficacy of nintedanib versus the comparator (pirfenidone) was then obtained from a Network Meta-Analysis (NMA) combining data reported in each primary study (INPULSIS 1-2 and TOMORROW trials for nintedanib, and CAPACITY and ASCEND trials for pirfenidone, respectively). At base-case, treatment with nintedanib resulted in a slightly lower estimated total cost vs pirfenidone, better safety profile and lower risk of acute exacerbations with an advantage in Quality Adjusted Life years (QALYs) gained. These results were confirmed by the sensitivity analysis. Although nintedanib appears to be a valuable option for the NHS to treat IPF patients, future data evidence, as long-term or real-life data, will help to confirm these results.[In Italian]

scholarly journals Effects of Pirfenidone on Echocardiographic Parameters of Left Ventricular Structure and Function in Patients with Idiopathic Pulmonary Fibrosis

2020 ◽  
Vol 5 (2) ◽  
pp. 35-42
Author(s):  
Shehab Al-Ansari ◽  
Allen Borowski ◽  
Ali Fuad ◽  
Omar Alawadhi ◽  
Haris Riaz ◽  
...  
Keyword(s):  
Treatment Group ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Diastolic Dysfunction ◽  
Left Ventricular ◽  
Structure And Function ◽  
Control Group ◽  
Lv Function ◽  
Echocardiographic Parameters ◽  
And Function

AbstractAim: Pirfenidone is a novel anti-fibrotic agent utilized in the treatment of idiopathic pulmonary fibrosis (IPF). It has been implicated in mitigating myocardial fibrosis and left ventricular (LV) systolic and diastolic dysfunction in animal models. However, its impact on LV mechanics in humans remains unknown. The aim of this study was to retrospectively evaluate the effects of pirfenidone on echocardiographic parameters of LV function and structure in patients with IPF.Methods: A total of 124 patients with IPF were included in this study: 64 patients treated with pirfenidone (treatment group) and 60 patients not taking pirfenidone (control group), who had serial pretreatment/baseline and posttreatment/follow-up echocardiograms done within a time frame of four years. Changes in the means of parameters of LV function (systolic, diastolic, and global longitudinal strain) and LV structure (mass and volume indices) were compared between the treatment and control groups. This was followed by a subgroup analysis that included only 88 patients (47 treated, 41 controls) with echocardiographic evidence of myocardial dysfunction at baseline (defined as an ejection fraction of ≤45, or diastolic dysfunction stage 1 or more) in addition to a known clinical diagnosis of congestive heart failure. To account for potential confounders, a secondary adjusted analysis by way of 1:1 propensity score matching (PSM) was carried out. This yielded a sample consisting of 62 patients with 56 patients in the subgroup cohort.Results: Patients in the treatment group were significantly younger (69.4 vs. 77 years, p<0.001) and had relatively lower forced vital capacity (69.9% vs. 80.6%, p = 0.005) in comparison to the control group. However, after PSM, the age demographics were comparable between both groups (72.18 vs. 72.15, p = 0.9). In the primary unadjusted analysis, there was no statistically significant change in any of the mean parameters of LV function and structure after pirfenidone administration when compared to the control group. Furthermore, no significant differences were noted in the subgroup cohort. Such findings were re-demonstrated after a secondary analysis with PSM.Conclusion: From an echocardiographic perspective, pirfenidone had no significant effects on LV structure and function in patients with IPF, even in patients with more overt cardiac dysfunction.

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