Cell Death Dis. 2023 Jun 30;14(6):389. doi: 10.1038/s41419-023-05889-8.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a devastating fibrotic lung disease characterized by scarring and destruction of the lung architecture, with limited treatment options. Targeted gene therapy to restore cell division autoantigen-1 (CDA1) expression may be a potential treatment approach to delay the progression of pulmonary fibrosis (PF). Here, we focused on CDA1, which was significantly decreased in human IPF, in a mouse model of bleomycin (BLM)-induced PF, and in transforming growth factor (TGF-β)-challenged lung fibroblasts. In vitro, CDA1 overexpression by lentivirus infection in human embryonic lung fibroblasts (HFL1 cells) inhibited the production of pro-fibrotic and pro-inflammatory cytokines, lung fibroblast-to-myofibroblast transition, and extracellular matrix protein expression induced by exogenous TGF-β1 treatment, whereas CDA1 knockdown with small interfering RNA promoted this effect. CDA1 overexpression also inhibited cell proliferation and migration. In a mouse model of BLM-induced PF, we provided novel evidence that the intratracheal delivery of adeno-associated virus serotype 9 carrying the mouse Tspyl2 gene reduced lung tissue inflammation and fibrosis. Mechanistically, CDA1, as a transcription regulator, could repress the TGF-β signal transduction in vivo and in vitro. In conclusion, our results show that Tspyl2 gene therapy plays an antifibrotic role by inhibiting the lung fibroblast-to-myofibroblast transition and downstream TGF-β/Smad3 signaling transduction in BLM-induced PF in mice, suggesting that CDA1 is an appropriate and promising therapeutic target for PF.

PMID:37391440 | DOI:10.1038/s41419-023-05889-8

Chem Biomed Eng. 2023 May 22;1(3):268-285. doi: 10.1021/cbmi.3c00023. eCollection 2023 Jun 26.

ABSTRACT

Chronic lung diseases, such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), are major leading causes of death worldwide and are generally associated with poor prognoses. The heterogeneous distribution of collagen, mainly type I collagen associated with excessive collagen deposition, plays a pivotal role in the progressive remodeling of the lung parenchyma to chronic exertional dyspnea for both IPF and COPD. To address the pressing need for noninvasive early diagnosis and drug treatment monitoring of pulmonary fibrosis, we report the development of human collagen-targeted protein MRI contrast agent (hProCA32.collagen) to specifically bind to collagen I overexpressed in multiple lung diseases. When compared to clinically approved Gd3+ contrast agents, hProCA32.collagen exhibits significantly better r1 and r2 relaxivity values, strong metal binding affinity and selectivity, and transmetalation resistance. Here, we report the robust detection of early and late-stage lung fibrosis with stage-dependent MRI signal-to-noise ratio (SNR) increase, with good sensitivity and specificity, using a progressive bleomycin-induced IPF mouse model. Spatial heterogeneous mapping of usual interstitial pneumonia (UIP) patterns with key features closely mimicking human IPF, including cystic clustering, honeycombing, and traction bronchiectasis, were noninvasively detected by multiple MR imaging techniques and verified by histological correlation. We further report the detection of fibrosis in the lung airway of an electronic cigarette-induced COPD mouse model, using hProCA32.collagen-enabled precision MRI (pMRI), and validated by histological analysis. The developed hProCA32.collagen is expected to have strong translational potential for the noninvasive detection and staging of lung diseases, and facilitating effective treatment to halt further chronic lung disease progression.

PMID:37388961 | PMC:PMC10302889 | DOI:10.1021/cbmi.3c00023

Chin Med J Pulm Crit Care Med. 2023 Jun;1(2):77-83. doi: 10.1016/j.pccm.2022.12.002. Epub 2023 Jan 23.

ABSTRACT

The pandemic of coronavirus disease 2019 (COVID‑19), caused by a novel severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), has caused an enormous impact on the global healthcare. SARS-CoV-2 infection primarily targets the respiratory system. Although most individuals testing positive for SARS-CoV-2 present mild or no upper respiratory tract symptoms, patients with severe COVID-19 can rapidly progress to acute respiratory distress syndrome (ARDS). ARDS-related pulmonary fibrosis is a recognized sequelae of COVID-19. Whether post-COVID-19 lung fibrosis is resolvable, persistent, or even becomes progressive as seen in human idiopathic pulmonary fibrosis (IPF) is currently not known and remains a matter of debate. With the emergence of effective vaccines and treatments against COVID-19, it is now important to build our understanding of the long-term sequela of SARS-CoV-2 infection, to identify COVID-19 survivors who are at risk of developing chronic pulmonary fibrosis, and to develop effective anti-fibrotic therapies. The current review aims to summarize the pathogenesis of COVID-19 in the respiratory system and highlights ARDS-related lung fibrosis in severe COVID-19 and the potential mechanisms. It envisions the long-term fibrotic lung complication in COVID-19 survivors, in particular in the aged population. The early identification of patients at risk of developing chronic lung fibrosis and the development of anti-fibrotic therapies are discussed.

PMID:37388822 | PMC:PMC9988550 | DOI:10.1016/j.pccm.2022.12.002

Pol Arch Intern Med. 2023 Jun 30:16520. doi: 10.20452/pamw.16520. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive and life-threatening interstitial lung disease of familial or sporadic onset. The incidence and prevalence of IPF is in the range of 0.09-1.30 and 0.33-4.51 per 10,000 persons, respectively. IPF has a poor prognosis, and death usually occurring within 2-5 years following the diagnosis due to secondary respiratory failure. Currently, there are two drugs available to treat IPF, prirfenidone and nintedanib, both only slow the disease progression and, in addition, have unfavorable safety profiles. IPF bears the histology of usual interstitial pneumonia, which is characterized by bronchiolization of distal airspaces, honeycombing, fibroblastic foci, and abnormal epithelial hyperplasia. In the last years, alterations in metabolic pathways, in particular, those associated with fatty acid (FA) metabolism have been link to the pathogenesis of lung fibrosis. Changes in FA profiles have been reported in lung tissue, plasma, and bronchoalveolar lavage fluid of IPF patients and have been found to correlate with the disease progression and outcome. In addition, they have been associated with the development of a pro-fibrotic phenotype of epithelial cells, macrophages, and fibroblasts/myofibroblasts contributing to their (trans)differentiation and production of disease relevant mediators. Furthermore, strategies focusing on the correction of FA profiles in experimental models of lung fibrosis brought advances in understanding tissue scarring processes and contributed to the transition of new molecules into clinical development. This review highlights the role of FA and their metabolites in IPF and provides evidence for therapeutic potential of lipidome manipulations in the treatment of this disease.

PMID:37387676 | DOI:10.20452/pamw.16520

Clin Exp Rheumatol. 2023 Aug;41(8):1670-1678. doi: 10.55563/clinexprheumatol/icr6hy. Epub 2023 Jun 29.

ABSTRACT

OBJECTIVES: Studies identifying nonspecific interstitial pneumonia (NSIP) as the predominant histopathology in systemic sclerosis-associated interstitial lung disease (SSc-ILD) have primarily utilised surgical lung biopsies in early disease. These case series may only reflect the histopathology of early disease and differ from the histopathology of advanced disease in those with respiratory failure.

METHODS: Patients receiving a lung transplant for a diagnosis of SSc at a single centre from 2000-2021 were included for retrospective analysis. All explanted lungs underwent histopathology review as part of routine care.

RESULTS: 127 patients with SSc received a native lung transplant during the study period. Usual interstitial pneumonia (UIP) was identified in 111 explants (87.4%), NSIP in 45 (35.4%) explants, organising pneumonia in 11 explants (8.7%), and lymphocytic bronchitis in 2 explants (1.6%). Areas of both UIP and NSIP were identified in 37 explants (29.1%), with only 9 explants (7.1%) showing neither UIP nor NSIP. Aspiration was identified on histology in 49 (38.6%) explants. Pathology results were available from a prior surgical lung biopsy for 19 patients, with 11 patients maintaining the same primary pathology on biopsy and explant (2 NSIP, 9 UIP) and 8 patients showing different pathology at the timepoints, all of whom had UIP on explant. Most patients (101, 79.5%) had evidence of pulmonary hypertension and vasculopathy on explant.

CONCLUSIONS: UIP is the predominant histopathology in patients with SSc receiving a lung transplant, with many patients concurrently having both NSIP and UIP or showing progression from NSIP to UIP over time before transplant.

PMID:37382449 | DOI:10.55563/clinexprheumatol/icr6hy

J Clin Invest. 2023 Jun 29:e165976. doi: 10.1172/JCI165976. Online ahead of print.

NO ABSTRACT

PMID:37384419 | DOI:10.1172/JCI165976

Am J Respir Crit Care Med. 2023 Jun 29. doi: 10.1164/rccm.202210-1947OC. Online ahead of print.

ABSTRACT

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease for which novel therapies are needed. External controls (ECs) could enhance IPF trial efficiency, though the direct comparability of ECs to concurrent controls is unknown.

OBJECTIVES: To develop IPF ECs by fit for purpose data standards to historical randomized clinical trial (RCT), multicenter registry (Pulmonary Fibrosis Foundation Patient Registry [PFF-PR]), and electronic health record (EHR) data and to evaluate endpoint comparability among ECs and the BMS-986020 phase 2 RCT.

METHODS: After data curation, the rate of change in forced vital capacity (FVC) from baseline to 26 weeks among participants receiving BMS-986020 600 mg twice daily was compared with the BMS-placebo arm and ECs using mixed effects models with inverse probability weights.

MEASUREMENTS AND MAIN RESULTS: At 26 weeks, the rate of change in FVC was -32.71 mL (BMS-986020) versus -130.09 mL (BMS-placebo; difference, 97.4 mL, 95% CI, 24.6, 170.2), replicating the original BMS-986020 RCT. RCT-ECs showed treatment effect point estimates within the 95% CI of the original BMS-986020 RCT. Both PFF-PR-ECs and EHR-ECs experienced a slower rate of FVC decline compared with the BMS-placebo arm, resulting in treatment effect point estimates outside of the 95% CI of the original BMS-986020 RCT.

CONCLUSIONS: IPF ECs generated from historical RCT placebo arms result in comparable primary treatment effects to that of the original clinical trial, while ECs from real-world data sources, including registry or EHR data, do not. RCT-ECs may serve as a potentially useful supplement to future IPF RCTs.

PMID:37384378 | DOI:10.1164/rccm.202210-1947OC

Front Med (Lausanne). 2023 Jun 13;10:1117071. doi: 10.3389/fmed.2023.1117071. eCollection 2023.

ABSTRACT

The aim of this review is to examine and evaluate published literature associated with idiopathic inflammatory myopathies (IIM) and interstitial lung disease (ILD) based on myositis specific autoantibodies (MSA) and the potential clinical significance of each autoantibody subtype for the practicing clinician. The review is a comprehensive search of literature published in PubMed from the year 2005 and onward coinciding with the surge in the discovery of new MSAs. Additionally, we comment on recommended multidisciplinary longitudinal care practices for patients with IIM-ILD with regard to imaging and other testing. Treatment is not covered in this review.

PMID:37384043 | PMC:PMC10296774 | DOI:10.3389/fmed.2023.1117071

Front Physiol. 2023 Jun 13;14:1205924. doi: 10.3389/fphys.2023.1205924. eCollection 2023.

ABSTRACT

Some patients with idiopathic pulmonary fibrosis present impaired ventilatory variables characterised by low forced vital capacity values associated with an increase in respiratory rate and a decrease in tidal volume which could be related to the increased pulmonary stiffness. The lung stiffness observed in pulmonary fibrosis may also have an effect on the functioning of the brainstem respiratory neural network, which could ultimately reinforce or accentuate ventilatory alterations. To this end, we sought to uncover the consequences of pulmonary fibrosis on ventilatory variables and how the modification of pulmonary rigidity could influence the functioning of the respiratory neuronal network. In a mouse model of pulmonary fibrosis obtained by 6 repeated intratracheal instillations of bleomycin (BLM), we first observed an increase in minute ventilation characterised by an increase in respiratory rate and tidal volume, a desaturation and a decrease in lung compliance. The changes in these ventilatory variables were correlated with the severity of the lung injury. The impact of lung fibrosis was also evaluated on the functioning of the medullary areas involved in the elaboration of the central respiratory drive. Thus, BLM-induced pulmonary fibrosis led to a change in the long-term activity of the medullary neuronal respiratory network, especially at the level of the nucleus of the solitary tract, the first central relay of the peripheral afferents, and the Pre-Bötzinger complex, the inspiratory rhythm generator. Our results showed that pulmonary fibrosis induced modifications not only of pulmonary architecture but also of central control of the respiratory neural network.

PMID:37383147 | PMC:PMC10293840 | DOI:10.3389/fphys.2023.1205924

Sarcoidosis Vasc Diffuse Lung Dis. 2023 Jun 29;40(2):e2023021. doi: 10.36141/svdld.v40i2.14634.

ABSTRACT

BACKGROUND AND AIM: New parameters in the 6-minute walk test (6MWT) are needed for assessing exercise capacity in patients with idiopathic pulmonary fibrosis (IPF). To our knowledge, no previous study has investigated the potential of using the desaturation distance ratio (DDR) to assess exercise capacity specifically in patients with IPF. This study aimed to investigate whether DDR is a potential tool for assessing the exercise capacity of patients with IPF.

METHODS: This study conducted with 33 subjects with IPF. Pulmonary function tests and a 6MWT were performed. To calculate the DDR, first, the difference between the patient's SpO2 at each minute and the SpO2 of 100% was summed together to determine the desaturation area (DA). Next, DDR was calculated using dividing DA by the 6-minute walk test distance (6MWD) (i.e., DA/6MWD).

RESULTS: When correlations of 6MWD and DDR with changes (Δ) in the severity of perceived dyspnea were examined, 6MWD did not significantly correlate with ΔBorg. Conversely, there was a significant correlation between the DDR and ΔBorg (r= 0.488, p=0.004). There were significant correlations between 6MWD and FVC % (r=0.370, p=0.034), and FEV1 % (r=0.465, p=0.006). However, DDR was significantly more correlated with FVC % (r= -0.621, p< 0.001), FEV1 % (r= -0.648, p< 0.001). Moreover, there was a significant correlation between DDR and DLCO % (r= -0.342, p=0.052).

CONCLUSIONS: The findings of this study suggest that DDR is a promising and more useful parameter for assessing patients with IPF.

PMID:37382067 | DOI:10.36141/svdld.v40i2.14634

Respiration. 2023;102(7):526-527. doi: 10.1159/000531025. Epub 2023 Jun 28.

NO ABSTRACT

PMID:37379825 | DOI:10.1159/000531025

Clin Pharmacol Drug Dev. 2023 Jun 28. doi: 10.1002/cpdd.1294. Online ahead of print.

ABSTRACT

Approved treatments for idiopathic pulmonary fibrosis have tolerability concerns and limited efficacy. CC-90001, a c-Jun N-terminal kinase inhibitor, is under investigation as a therapy for fibrotic diseases. A Phase 1b safety, pharmacokinetics, and pharmacodynamics study of oral CC-90001 (100, 200, or 400 mg) administered once daily for 12 weeks was conducted in patients with pulmonary fibrosis (NCT02510937). Sixteen patients with a mean age of 68 years were studied. The most common treatment-emergent adverse events were nausea and headache; all events were of mild or moderate intensity. Pharmacokinetic profiles were similar between the patients in this trial and healthy adults in previous studies. Forced vital capacity increased in the 200- and 400-mg cohorts from baseline to Week 12, and dose-dependent reductions in fibrosis biomarkers were observed. Antifibrotic activity of CC-90001 was also evaluated in vitro in transforming growth factor beta 1 (TGF-β1)-stimulated cells. CC-90001 reduced in vitro profibrotic gene expression in both lung epithelial cells and fibroblasts, supporting a potential direct antifibrotic action of c-Jun N-terminal kinase inhibition in either or both cell types. Overall, CC-90001 was generally safe and well tolerated, and treatment was associated with forced vital capacity improvement and reductions in profibrotic biomarkers.

PMID:37378860 | DOI:10.1002/cpdd.1294

ERJ Open Res. 2023 Jun 26;9(3):00080-2023. doi: 10.1183/23120541.00080-2023. eCollection 2023 May.

ABSTRACT

A measure of regional gas exchange on HP 129Xe MRI was able to detect apparent improvements in IPF patients treated with antifibrotic medication after 1 year, while no such improvements were found in patients treated with conventional therapies https://bit.ly/3ZXipzD.

PMID:37377660 | PMC:PMC10291299 | DOI:10.1183/23120541.00080-2023

Respirology. 2023 Jun 27. doi: 10.1111/resp.14543. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Studies of autoimmunity and anti-citrullinated protein antibodies (ACPA) in idiopathic pulmonary fibrosis (IPF) have been confined to investigations of anti-cyclic citrullinated peptide (anti-CCP) antibodies which utilize synthetic peptides as surrogate markers for in vivo citrullinated antigens. We studied immune activation by analysing the prevalence of in vivo anti-modified protein antibodies (AMPA) in IPF.

METHODS: We included patients with incident and prevalent IPF (N = 120), sex and smoking-matched healthy controls (HC) (N = 120) and patients with RA (N = 104). Serum (median time: 11 months [Q1-Q3: 1-28 months] from diagnosis) was analysed for presence of antibodies towards native and posttranslational modified (citrullinated [Cit, N = 25]; acetylated [Acet, N = 4] and homocitrullinated [Carb, N = 1]) peptides derived from tenascin (TNC, N = 9), fibrinogen (Fib, N = 11), filaggrin (Fil, N = 5), histone (N = 8), cathelicidin (LL37, N = 4) and vimentin (N = 5) using a custom-made peptide microarray.

RESULTS: AMPA were more frequent and in increased levels in IPF than in HC (44% vs. 27%, p < 0.01), but less than in RA (44% vs. 79%, p < 0.01). We specifically observed AMPA in IPF towards certain citrullinated, acetylated and carbamylated peptides versus HC: tenascin (Cit(2033) -TNC2025-2040 ; Cit(2197) -TNC2177-2200 ; Cit(2198) -TNC2177-2200 ), fibrinogen (Cit(38,42) -Fibα36-50 ; Cit(72) -Fibβ60-74 ) and filaggrin (Acet-Fil307-324 , Carb-Fil307-324 ). No differences in survival (p = 0.13) or disease progression (p = 0.19) between individuals with or without AMPA was observed in IPF. However, patients with incident IPF had better survival if AMPA were present (p = 0.009).

CONCLUSION: A significant proportion of IPF patients present with specific AMPA in serum. Our results suggest autoimmunity as a possible characteristic for a subgroup of IPF that may affect disease outcome.

PMID:37376768 | DOI:10.1111/resp.14543

Molecules. 2023 Jun 9;28(12):4665. doi: 10.3390/molecules28124665.

ABSTRACT

Idiopathic pulmonary fibrosis is a progressive, irreversible lung disease that leads to respiratory failure and death. Vincamine is an indole alkaloid obtained from the leaves of Vinca minor and acts as a vasodilator. The present study aims to investigate the protective activity of vincamine against EMT in bleomycin (BLM)-induced pulmonary fibrosis via assessing the apoptotic and TGF-β1/p38 MAPK/ERK1/2 signaling pathways. In bronchoalveolar lavage fluid, protein content, total cell count, and LDH activity were evaluated. N-cadherin, fibronectin, collagen, SOD, GPX, and MDA levels were determined in lung tissue using ELISA. Bax, p53, bcl2, TWIST, Snai1, and Slug mRNA levels were examined using qRT-PCR. Western blotting was used to assess the expression of TGF-β1, p38 MAPK, ERK1/2, and cleaved caspase 3 proteins. H & E and Masson's trichrome staining were used to analyze histopathology. In BLM-induced pulmonary fibrosis, vincamine reduced LDH activity, total protein content, and total and differential cell count. SOD and GPX were also increased following vincamine treatment, while MDA levels were decreased. Additionally, vincamine suppressed the expression of p53, Bax, TWIST, Snail, and Slug genes as well as the expression of factors such as TGF-β1, p/t p38 MAPK, p/t ERK1/2, and cleaved caspase 3 proteins, and, at the same time, vincamine increased bcl2 gene expression. Moreover, vincamine restored fibronectin, N-Catherine, and collagen protein elevation due to BLM-induced lung fibrosis. In addition, the histopathological examination of lung tissues revealed that vincamine attenuated the fibrotic and inflammatory conditions. In conclusion, vincamine suppressed bleomycin-induced EMT by attenuating TGF-β1/p38 MAPK/ERK1/2/TWIST/Snai1/Slug/fibronectin/N-cadherin pathway. Moreover, it exerted anti-apoptotic activity in bleomycin-induced pulmonary fibrosis.

PMID:37375218 | DOI:10.3390/molecules28124665

Int J Mol Sci. 2023 Jun 15;24(12):10196. doi: 10.3390/ijms241210196.

ABSTRACT

Interstitial lung diseases (ILDs) are a large group of pulmonary disorders characterized histologically by the cardinal involvement of the pulmonary interstitium. The prototype of ILDs is idiopathic pulmonary fibrosis (IPF), an incurable disease characterized by progressive distortion and loss of normal lung architecture through unchecked collagen deposition. Acute exacerbations are dramatic events during the clinical course of ILDs, associated with high morbidity and mortality. Infections, microaspiration, and advanced lung disease might be involved in the pathogenesis of acute exacerbations. Despite clinical scores, the prediction of the onset and outcome of acute exacerbations is still inaccurate. Biomarkers are necessary to characterize acute exacerbations better. We review the evidence for alveolar epithelial cell, fibropoliferation, and immunity molecules as potential biomarkers for acute exacerbations of interstitial lung disease.

PMID:37373339 | DOI:10.3390/ijms241210196

Int J Mol Sci. 2023 Jun 15;24(12):10182. doi: 10.3390/ijms241210182.

ABSTRACT

Novel genetic and epigenetic factors involved in the development and prognosis of idiopathic pulmonary fibrosis (IPF) have been identified. We previously observed that erythrocyte membrane protein band 4.1-like 3 (EPB41L3) increased in the lung fibroblasts of IPF patients. Thus, we investigated the role of EPB41L3 in IPF by comparing the EPB41L3 mRNA and protein expression of lung fibroblast between patients with IPF and controls. We also investigated the regulation of epithelial-mesenchymal transition (EMT) in an epithelial cell line (A549) and fibroblast-to-myofibroblast transition (FMT) in a fibroblast cell line (MRC5) by overexpressing and silencing EPB41L3. EPB41L3 mRNA and protein levels, as measured using RT-PCR, real-time PCR, and Western blot, were significantly higher in fibroblasts derived from 14 IPF patients than in those from 10 controls. The mRNA and protein expression of EPB41L3 was upregulated during transforming growth factor-β-induced EMT and FMT. Overexpression of EPB41L3 in A549 cells using lenti-EPB41L3 transfection suppressed the mRNA and protein expression of N-cadherin and COL1A1. Treatment with EPB41L3 siRNA upregulated the mRNA and protein expression of N-cadherin. Overexpression of EPB41L3 in MRC5 cells using lenti-EPB41L3 transfection suppressed the mRNA and protein expression of fibronectin and α-SMA. Finally, treatment with EPB41L3 siRNA upregulated the mRNA and protein expression of FN1, COL1A1, and VIM. In conclusion, these data strongly support an inhibitory effect of EPB41L3 on the process of fibrosis and suggest the therapeutic potential of EPB41L3 as an anti-fibrotic mediator.

PMID:37373330 | DOI:10.3390/ijms241210182

Int J Mol Sci. 2023 Jun 14;24(12):10125. doi: 10.3390/ijms241210125.

ABSTRACT

The deadly interstitial lung condition known as idiopathic pulmonary fibrosis (IPF) worsens over time and for no apparent reason. The traditional therapy approaches for IPF, which include corticosteroids and immunomodulatory drugs, are often ineffective and can have noticeable side effects. The endocannabinoids are hydrolyzed by a membrane protein called fatty acid amide hydrolase (FAAH). Increasing endogenous levels of endocannabinoid by pharmacologically inhibiting FAAH results in numerous analgesic advantages in a variety of experimental models for pre-clinical pain and inflammation. In our study, we mimicked IPF by administering intratracheal bleomycin, and we administered oral URB878 at a dose of 5 mg/kg. The histological changes, cell infiltration, pro-inflammatory cytokine production, inflammation, and nitrosative stress caused by bleomycin were all reduced by URB878. Our data clearly demonstrate for the first time that the inhibition of FAAH activity was able to counteract not only the histological alteration bleomycin-induced but also the cascade of related inflammatory events.

PMID:37373275 | DOI:10.3390/ijms241210125

Biomedicines. 2023 Jun 17;11(6):1739. doi: 10.3390/biomedicines11061739.

ABSTRACT

This review brings together the current knowledge regarding the risk factors and the clinical, radiologic, and histological features of both post-COVID-19 pulmonary fibrosis (PCPF) and idiopathic pulmonary fibrosis (IPF), describing the similarities and the disparities between these two diseases, using numerous databases to identify relevant articles published in English through October 2022. This review would help clinicians, pathologists, and researchers make an accurate diagnosis, which can help identify the group of patients selected for anti-fibrotic therapies and future therapeutic perspectives.

PMID:37371834 | DOI:10.3390/biomedicines11061739

Biomedicines. 2023 Jun 16;11(6):1728. doi: 10.3390/biomedicines11061728.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a disease that causes scarring and fibrotic transformation of the lung parenchyma, resulting in the progressive loss of respiratory function and, often, death. Current treatments that target profibrotic factors can slow the rate of progression but are unable to ultimately stop it. In the past decade, many studies have shown that increased vascular permeability may be both a predictive and perpetuating factor in fibrogenesis. Consequently, there is a search for therapeutic targets to try and modulate vascular permeability in fibrotic lungs. One such class of targets that show great promise is sphingolipids. Sphingolipids are common in cell membranes and are increasingly recognized as critical to many cell signaling pathways, including those that affect the integrity of the vascular endothelial barrier. In this focused review we look at sphingolipids, particularly the sphingosine-1-phosphate (S1P) axis and its effects on vascular permeability, and how those effects may affect the pathogenesis of IPF. We further examine existing S1P modulators and their potential efficacy as therapeutics for IPF.

PMID:37371823 | DOI:10.3390/biomedicines11061728