Soy isoflavones reduce asthma exacerbation in asthmatic patients with high PAI-1–producing genotypes

Jo, Ara; Casale, Thomas B.; Jeong, Su Jin; Hong, Seung Jae; Cho, Joong K.; Holbrook, Janet T.; Kumar, Rajesh; Smith, Lewis J.

doi:10.1016/j.jaci.2019.01.020

Cited by 19 publications

(14 citation statements)

References 28 publications

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“…Previous studies report that elevated SERPINE1 levels are correlated with cellular senescence and the aging process ( Yamamoto et al, 2005 ; Kortlever et al, 2006 ; Eren et al, 2014 ). We have been studying the role of PAI-1 in the airway remodeling of asthma ( Cho et al, 2001 ; Jo et al, 2018 ; Cho et al, 2019 ). However, it has not been known about the role of PAI-1 in NP, especially in age-related roles.…”

Section: Discussionmentioning

confidence: 99%

Age-Related Increase of Collagen/Fibrin Deposition and High PAI-1 Production in Human Nasal Polyps

Choi

Han

et al. 2022

Front. Pharmacol.

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Objective: Our previous studies showed an age-related increased prevalence of nasal polyps (NP) and reduced production of S100A8/9 in elderly patients with chronic rhinosinusitis with NP (CRSwNP). In this study, we investigated an unbiased age-related gene expression profile in CRSwNP subjects and healthy controls, and further identified the differences in their tissue remodeling.Methods: Microarrays using NP and uncinate tissues from health controls (elderly, age ≥65 vs. non-elderly, age 18–49) were performed, and differentially regulated genes were analyzed. Quantitative real-time PCR (qPCR), Immunostaining, Periodic acid-Schiff (PAS), trichrome staining, Western blot, and ELISA were performed for further investigation.Results: Microarrays identified differentially expressed genes according to disease and age; 278 in NP vs. controls, 75 in non-elderly NP vs. non-elderly controls, and 32 in elderly NP vs. elderly controls. qPCR confirmed that the PLAT gene was downregulated and the SERPINB2 gene upregulated in NP vs. controls. The serous glandular cell-derived antimicrobial protein/peptide-related genes such as BPIFB3, BPIFB2, LPO, and MUC7 were remarkably reduced in NP, regardless of age. SERPINE1 gene (plasminogen activator inhibitor-1, PAI-1) expression was significantly increased in elderly NP versus elderly controls. IHC and western blot confirmed significantly decreased production of MUC7 and LPO in NP versus controls. There was a trend of age-related reduction of submucosal gland cells in normal controls. Trichrome and immunofluorescence staining demonstrated an age-related increase of collagen and fibrin deposition in NP, consistent with increased PAI-1 production.Conclusion: This study demonstrated age-related differential glandular remodeling patterns and fibrosis in NP and normal controls. PAI-1 expression was significantly increased in elderly NP versus elderly controls, suggesting PAI-1 as a potential treatment target in elderly NP.

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Section: Discussionmentioning

confidence: 99%

Age-Related Increase of Collagen/Fibrin Deposition and High PAI-1 Production in Human Nasal Polyps

Choi

Han

et al. 2022

Front. Pharmacol.

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“…It has been shown that upregulation of plasminogen activator inhibitor‐1 (PAI‐1) leads to asthma exacerbations. Genistein is found to decrease the level of TGF‐β1‐induce‐PAI‐1 in the epithelial cells of the airways in asthmatic patients (Cho et al., 2019). In the study by Pintova et al, it has been reported that oral treatment with genistein prior to chemotherapy in metastatic colorectal cancer patients has significantly reduced chemotherapy‐related adverse events and was found to be safe and tolerable (Pintova et al., 2019).…”

Section: Clinical Significance Of Genistein With Respect To Recent Clinical Trialsmentioning

confidence: 99%

Cellular and molecular mechanisms of genistein in prevention and treatment of diseases: An overview

Nazari-Khanamiri

Ghasemnejad‐Berenji

2021

J Food Biochem

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Genistein is the simplest secondary metabolite in soybeans and belongs to a group of compounds called isoflavones. It is a phytoestrogen and it makes up more than 60% of soy isoflavones. Studies have shown the anti‐inflammatory, anti‐apoptotic, and anti‐angiogenic effects of genistein in addition to its modulatory effects on steroidal hormone receptors. In this review, we discuss the pharmacologic and therapeutic effects of genistein on various diseases. Practical applications In this review, we have discussed the therapeutic effects of genistein as the main constituent of soybeans on health conditions. Its antioxidant, anti‐inflammatory, anti‐apoptotic and, anti‐angiogenic effects need more attention. The pharmacological properties of genistein make this natural isoflavone a potential treatment for various diseases such as postmenopausal symptoms, cancer, bone, brain, and heart diseases. Special emphasis should be given to it, resulting in using it in clinical as a safe, potent, and bioactive molecule.

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“…These consists of small double-stranded RNA fragments capable of triggering the degradation of a specific mRNA [7] and therefore ultimately capable of blocking the synthesis of certain proteins. Recently, the true efficacy of siRNA directed against particular targets, such as STAT6, PAI-1, and Syk for the treatment of asthma was demonstrated through appropriate in vitro and in vivo studies [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

“…The conventional therapies, therefore, are often associated with a series of limitations that have pushed the research towards the identification of new biological targets for treatment of the pathology. It has been seen that in individuals suffering from asthma there is overexpression of numerous genes and proteins, such as Signal Transducer and Activator of Transcription 6 (STAT6) [4], Plasminogen Activator Inhibitor-1 (PAI-1) [5], and Spleen Tyrosine Kinase (Syk) [6]. In particular, STAT6 regulates the T helper type 2 (Th 2 ) immune response, PAI-1 is associated with asthma severity because of its role in airway remodeling, while Syk is implicated as central immune modulator promoting allergic airway inflammation; thus, their inhibition could be an effective therapeutic approach in asthma.…”

Section: Introductionmentioning

confidence: 99%

Design of New Polyaspartamide Copolymers for siRNA Delivery in Antiasthmatic Therapy

et al. 2020

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Here, a novel protonable copolymer was realized for the production of polyplexes with a siRNA (inhibitor of STAT6 expression in asthma), with the aim of a pulmonary administration. The polycation was synthesized by derivatization of α,β-poly(N-2-hydroxyethyl)d,l-aspartamide (PHEA) with 1,2-Bis(3-aminopropylamino)ethane (bAPAE) in proper conditions to obtain a PHEA-g-bAPAE graft copolymer with a derivatization degree in amine (DDbAPAE%) equal to 35 mol%. The copolymer showed a proper buffering behavior, i.e., ranging between pH 5 and 7.4, to potentially give the endosomal escape of the obtained polycations. In effect, an in vitro experiment demonstrated the effect on biological membranes of the copolymer on bronchial epithelial cells (16-HBE) strongly dependent on the pH of the medium, i.e., higher at pH 5. bAPAE-based copolymers were further obtained with an increasing pegylation degree, i.e., equal to 1.9, 2.7, and 4.4 mol%, respectively. All the obtained copolymers were able to complex siRNA at a N/P ratio that decreases as the pegylation degree increases. At the same time, the tendency of polyplexes to aggregate and the capability to interact with mucin also decreases as the pegylation in the copolymer increases. Gene silencing experiments on 16-HBE showed that these copolymers have a significant role in improving the intracellular transport of naked siRNA, where the presence of PEG does not seem to hinder the cellular uptake of polyplexes. The latter obtained at polymer/siRNA weight ratio (R) equal to 10 with PHEA-g-PEG(C)-g-bAPAE also seems to be not susceptible to the presence of mucin, avoiding the polyanionic exchange of complexed siRNA, thus showing adequate behavior to be used as an effective vector for siRNA.

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Soy isoflavones reduce asthma exacerbation in asthmatic patients with high PAI-1–producing genotypes

Cited by 19 publications

References 28 publications

Age-Related Increase of Collagen/Fibrin Deposition and High PAI-1 Production in Human Nasal Polyps

Age-Related Increase of Collagen/Fibrin Deposition and High PAI-1 Production in Human Nasal Polyps

Cellular and molecular mechanisms of genistein in prevention and treatment of diseases: An overview

Design of New Polyaspartamide Copolymers for siRNA Delivery in Antiasthmatic Therapy

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