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1.
Bratisl Lek Listy ; 123(9): 653-6958, 2022.
Статья в английский | MEDLINE | ID: covidwho-2024875

Реферат

PURPOSE: In addition to the highly variable clinical presentation of acute COVID-19 infection, it can also cause various post-acute signs and symptoms. In our study, we aimed to examine the efficacy of anti-fibrotic therapy in patients who developed pulmonary fibrosis after COVID-19. METHODS: In total, 15 patients who applied to the Post-Covid Outpatient Clinic between May 2021 and August 2021 and were diagnosed with COVID-19 pneumonia, and whose cough, dyspnea, exertional dyspnea and low saturation continued to be present at least 12 weeks after the diagnosis, were included in the study. Off-label pirfenidone treatment was started according to the radiological findings, pulmonary function test parameters (PFT) and 6-minute walking test (6MWT) results. The patients were followed up for 12 weeks. RESULTS: While all of the FVC, FVC%, FEV1, FEV1%, DLCO%, DLCO/VA%, 6MWT, and room air saturation levels were observed to increase statistically significantly in the patients at the 12th week, it was determined that there was a statistically significant decrease in the pulse level in room air (p = 0.01, 0.01, 0.01, 0.01, 0.004, 0.001, 0.002, 0.001, and 0.002, respectively). In regression analysis based on radiological scoring, it was observed that the DLCO and room air saturation levels at the 12th week of the treatment were statistically significantly higher in patients with lower scores at the beginning (p = 0.04, 0.03). In addition, it was observed that anti-fibrotic treatment, which was started in the earliest period, i.e., 12 weeks after the diagnosis, resulted in an improvement in radiological, PFT and 6MWT parameters. CONCLUSION: Patients who still had dyspnea and low saturation 12 weeks after the diagnosis, defined as chronic COVID-19, should be evaluated for anti-fibrotic therapy after the necessary radiological and PFT evaluation. Early treatment commencement brings about, besides radiological improvement, a better response obtained in PFT and 6MWT (Tab. 2, Fig. 2, Ref. 21).


Тема - темы
COVID-19 , Pulmonary Fibrosis , COVID-19/drug therapy , Dyspnea/etiology , Humans , Pulmonary Fibrosis/complications , Pulmonary Fibrosis/drug therapy , Respiratory Function Tests/adverse effects
2.
Int J Mol Sci ; 23(17)2022 Aug 26.
Статья в английский | MEDLINE | ID: covidwho-2023746

Реферат

Although interstitial lung disease (ILD) is a life-threatening pathological condition that causes respiratory failure, the efficiency of current therapies is limited. This study aimed to investigate the effects of human MIKO-1 (hMIKO-1), a hybrid protein that suppresses the abnormal activation of macrophages, on murine macrophage function and its therapeutic effect in a mouse model of bleomycin-induced ILD (BLM-ILD). To this end, the phenotype of thioglycolate-induced murine peritoneal macrophages co-cultured with hMIKO-1 was examined. The mice were assigned to normal, BLM-alone, or BLM + hMIKO-1 groups, and hMIKO-1 (0.1 mg/mouse) was administered intraperitoneally from day 0 to 14. The mice were sacrificed on day 28, and their lungs were evaluated by histological examination, collagen content, and gene expression levels. hMIKO-1 suppressed the polarization of murine macrophages to M2 predominance in vitro. The fibrosis score of lung pathology and lung collagen content of the BLM + hMIKO-1 group were significantly lower than those in the BLM-alone group. The expression levels of TNF-α, IL-6, IL-1ß, F4/80, and TIMP-1 in the lungs of the BLM + hMIKO-1 group were significantly lower than those in the BLM-alone group. These findings indicate that hMIKO-1 reduces lung fibrosis and may be a future therapeutic candidate for ILD treatment.


Тема - темы
Lung Diseases, Interstitial , Pulmonary Fibrosis , Animals , Bleomycin/toxicity , Collagen/metabolism , Disease Models, Animal , Humans , Lung/pathology , Lung Diseases, Interstitial/chemically induced , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/metabolism , Macrophages/metabolism , Mice , Mice, Inbred C57BL , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/metabolism
3.
Comput Methods Programs Biomed ; 225: 107094, 2022 Oct.
Статья в английский | MEDLINE | ID: covidwho-2007619

Реферат

BACKGROUND AND OBJECTIVE: Pulmonary fibrosis (PF) is a chronic progressive disease with an extremely high mortality rate and is a complication of COVID-19. Inhalable microspheres have been increasingly used in the treatment of lung diseases such as PF in recent years. Compared to the direct inhalation of drugs, a larger particle size is required to ensure the sustained release of microspheres. However, the clinical symptoms of PF may lead to the easier deposition of microspheres in the upper respiratory tract. Therefore, it is necessary to understand the effects of PF on the deposition of microspheres in the respiratory tract. METHODS: In this study, airway models with different degrees of PF in humans and mice were established, and the transport and deposition of microspheres in the airway were simulated using computational fluid dynamics. RESULTS: The simulation results showed that PF increases microsphere deposition in the upper respiratory tract and decreases bronchial deposition in both humans and mice. Porous microspheres with low density can ensure deposition in the lower respiratory tract and larger particle size. In healthy and PF humans, porous microspheres of 10 µm with densities of 700 and 400 kg/m³ were deposited most in the bronchi. Unlike in humans, microspheres larger than 4 µm are completely deposited in the upper respiratory tract of mice owing to their high inhalation velocity. For healthy and PF mice, microspheres of 6 µm with densities of and 100 kg/m³ are recommended. CONCLUSIONS: The results showed that with the exacerbation of PF, it is more difficult for microsphere particles to deposit in the subsequent airway. In addition, there were significant differences in the deposition patterns among the different species. Therefore, it is necessary to process specific microspheres from different individuals. Our study can guide the processing of microspheres and achieve differentiated drug delivery in different subjects to maximize therapeutic effects.


Тема - темы
COVID-19 , Pulmonary Fibrosis , Animals , Computer Simulation , Delayed-Action Preparations , Humans , Lung , Mice , Microspheres , Models, Biological , Particle Size , Porosity , Pulmonary Fibrosis/drug therapy , Respiratory Aerosols and Droplets , Trachea
4.
Cells ; 11(16)2022 Aug 11.
Статья в английский | MEDLINE | ID: covidwho-1987666

Реферат

Pulmonary fibrosis (PF) is a feared outcome of many pulmonary diseases which results in a reduction in lung compliance and capacity. The development of PF is relatively rare, but it can occur secondary to viral pneumonia, especially COVID-19 infection. While COVID-19 infection and its complications are still under investigation, we can look at a similar outbreak in the past to gain better insight as to the expected long-term outcomes of COVID-19 patient lung function. In the current article, we review the literature relative to PF via PubMed. We also performed a literature search for COVID-related pathological changes in the lungs. Finally, the paper was reviewed and summarized based on the studies' integrity, relative, or power calculations. This article provides a narrative review that endeavors to elucidate the current understanding of the pathophysiological mechanisms underlying PF and therapeutic strategies. We also discussed the potential for preventing progression to the fibrotic state within the context of the COVID-19 pandemic. With the massive scale of the COVID-19 pandemic, we expect there should more instances of PF due to COVID-19 infection. Patients who survive severe COVID-19 infection may suffer from a high incidence of PF.


Тема - темы
COVID-19 , Pneumonia, Viral , Pulmonary Fibrosis , Humans , Lung/pathology , Pandemics , Pneumonia, Viral/pathology , Pulmonary Fibrosis/complications , Pulmonary Fibrosis/drug therapy
5.
Eur Rev Med Pharmacol Sci ; 26(13): 4872-4880, 2022 07.
Статья в английский | MEDLINE | ID: covidwho-1955404

Реферат

OBJECTIVE: Growing interest is directed to the outcomes of COVID-19 in survivors, both in the convalescent period and in the long-term, which are responsible for morbidity and quality of life deterioration. This article aims to describe the mechanisms supporting the possible use of NAC as an adjuvant treatment for post-COVID-19 pulmonary fibrosis. MATERIALS AND METHODS: A search was performed in PubMed/MEDLINE. RESULTS: Interstitial changes have been observed in the CT scan of COVID-19 pneumonia. In patients with respiratory outcomes in the post-COVID-19 stage, glutathione (GSH) deficiency was found and interpreted as a reaction to the inflammatory cascade caused by the viral infection, while the pathophysiological process of pulmonary fibrosis involves numerous cytokines, such as TGF-ß, TNF-α, IL-1, PDGF and VEGF. NAC has a good tolerability profile, is easily administered orally and inexpensively, and has antioxidant and anti-inflammatory effects that may target the pathophysiologic mechanisms involved in pulmonary fibrosis. It may revert GSH deficiency, exerts direct and indirect antioxidant activity, anti-inflammatory activity and improves immune T-cell response. CONCLUSIONS: The mechanism of action of NAC suggests a role in the treatment of pulmonary fibrosis induced by COVID-19.


Тема - темы
COVID-19 , Pulmonary Fibrosis , Acetylcysteine/pharmacology , Acetylcysteine/therapeutic use , Anti-Inflammatory Agents , Antioxidants/pharmacology , COVID-19/drug therapy , Glutathione , Humans , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Quality of Life
6.
Int Immunopharmacol ; 109: 108805, 2022 Aug.
Статья в английский | MEDLINE | ID: covidwho-1814595

Реферат

Pulmonary vascular endothelial dysfunction is a key pathogenic mechanism in acute respiratory distress syndrome (ARDS), resulting in fibrosis in lung tissues, including in the context of COVID-19. Pirfenidone (PFD) has become a novel therapeutic agent for treating idiopathic pulmonary fibrosis (IPF) and can improve lung function, inhibit fibrosis and inhibit inflammation. Recently, endothelial-to-mesenchymal transition (EndMT) was shown to play a crucial role in various respiratory diseases. However, the role of PFD in the course of EndMT in LPS-induced ARDS remains poorly understood. The purpose of this study was to explore the anti-EndMT effects of PFD on pulmonary fibrosis after LPS-induced ARDS. First, we determined that PFD significantly reduced LPS-induced ARDS, as shown by significant pathological alterations, and alleviated the oxidative stress and inflammatory response in vitro and in vivo. Furthermore, PFD decreased pulmonary fibrosis in LPS-induced ARDS by inhibiting EndMT and reduced the expression levels of Hedgehog (HH) pathway target genes, such as Gli1 and α-SMA, after LPS induction. In summary, this study confirmed that inhibiting the HH pathway by PFD could decrease pulmonary fibrosis by downregulating EndMT in LPS-induced ARDS. In conclusion, we demonstrate that PFD is a promising agent to attenuate pulmonary fibrosis following ARDS in the future.


Тема - темы
Hedgehog Proteins , Pulmonary Fibrosis , Pyridones , Respiratory Distress Syndrome , Animals , Hedgehog Proteins/metabolism , Lipopolysaccharides , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Pyridones/pharmacology , Respiratory Distress Syndrome/chemically induced , Respiratory Distress Syndrome/drug therapy , Signal Transduction
8.
Nutrients ; 14(5)2022 Mar 05.
Статья в английский | MEDLINE | ID: covidwho-1732145

Реферат

BACKGROUND: Pulmonary fibrosis (PF) is a chronic, progressive, and, ultimately, terminal interstitial disease caused by a variety of factors, ranging from genetics, bacterial, and viral infections, to drugs and other influences. Varying degrees of PF and its rapid progress have been widely reported in post-COVID-19 patients and there is consequently an urgent need to develop an appropriate, cost-effective approach for the prevention and management of PF. AIM: The potential "therapeutic" effect of the tocotrienol-rich fraction (TRF) and carotene against bleomycin (BLM)-induced lung fibrosis was investigated in rats via the modulation of TGF-ß/Smad, PI3K/Akt/mTOR, and NF-κB signaling pathways. DESIGN/METHODS: Lung fibrosis was induced in Sprague-Dawley rats by a single intratracheal BLM (5 mg/kg) injection. These rats were subsequently treated with TRF (50, 100, and 200 mg/kg body wt/day), carotene (10 mg/kg body wt/day), or a combination of TRF (200 mg/kg body wt/day) and carotene (10 mg/kg body wt/day) for 28 days by gavage administration. A group of normal rats was provided with saline as a substitute for BLM as the control. Lung function and biochemical, histopathological, and molecular alterations were studied in the lung tissues. RESULTS: Both the TRF and carotene treatments were found to significantly restore the BLM-induced alterations in anti-inflammatory and antioxidant functions. The treatments appeared to show pneumoprotective effects through the upregulation of antioxidant status, downregulation of MMP-7 and inflammatory cytokine expressions, and reduction in collagen accumulation (hydroxyproline). We demonstrated that TRF and carotene ameliorate BLM-induced lung injuries through the inhibition of apoptosis, the induction of TGF-ß1/Smad, PI3K/Akt/mTOR, and NF-κB signaling pathways. Furthermore, the increased expression levels were shown to be significantly and dose-dependently downregulated by TRF (50, 100, and 200 mg/kg body wt/day) treatment in high probability. The histopathological findings further confirmed that the TRF and carotene treatments had significantly attenuated the BLM-induced lung injury in rats. CONCLUSION: The results of this study clearly indicate the ability of TRF and carotene to restore the antioxidant system and to inhibit proinflammatory cytokines. These findings, thus, revealed the potential of TRF and carotene as preventive candidates for the treatment of PF in the future.


Тема - темы
COVID-19 , Pulmonary Fibrosis , Tocotrienols , Animals , Bleomycin/toxicity , Carotenoids/adverse effects , Humans , NF-kappa B/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/prevention & control , Rats , Rats, Sprague-Dawley , SARS-CoV-2 , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Tocotrienols/adverse effects , Transforming Growth Factor beta/metabolism
9.
Am J Chin Med ; 50(1): 33-51, 2022.
Статья в английский | MEDLINE | ID: covidwho-1608685

Реферат

Qingfei Paidu decoction (QFPD) has been repeatedly recommended for the clinical treatment of novel coronavirus disease 2019 (COVID-19) in multiple provinces throughout China. A possible complication of COVID-19 lung involvement is pulmonary fibrosis, which causes chronic breathing difficulties and affects the patient's quality of life. Therefore, there is an important question regarding whether QFPD can alleviate the process of pulmonary fibrosis and its potential mechanisms. To explore this issue, this study demonstrated the anti-pulmonary fibrosis activity and mode of action of QFPD in vivo and in vitro pulmonary fibrosis models and network pharmacology. The results showed that QFPD effectively ameliorated the bleomycin-induced inflammation and collagen deposition in mice and significantly improved the epithelial-mesenchymal transition in pulmonary fibrosis in mice. In addition, QFPD inhibited bleomycin-induced M2 polarization of macrophages in pulmonary tissues. An in-depth study of the mechanism of QFPD in the treatment of pulmonary fibrosis based on network pharmacology and molecular simulation revealed that SRC was the main target of QFPD and sitosterol (a key compound in QFPD). QFPD and sitosterol regulate the EMT process and M2 polarization of macrophages by inhibiting the activation of SRC, thereby alleviating pulmonary fibrosis in mice. COVID-19 infection might produce severe fibrosis, and antifibrotic therapy with QFPD may be valuable in preventing severe neocoronavirus disease in patients with IPF, which could be a key factor explaining the role of QFPD in the treatment of COVID-19.


Тема - темы
COVID-19 , Pulmonary Fibrosis , Animals , Drugs, Chinese Herbal , Epithelial-Mesenchymal Transition , Humans , Mice , Mice, Inbred C57BL , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/etiology , Quality of Life , SARS-CoV-2
10.
Am J Chin Med ; 49(8): 1965-1999, 2021.
Статья в английский | MEDLINE | ID: covidwho-1599109

Реферат

Pulmonary fibrosis (PF) is a chronic and irreversible interstitial lung disease that even threatens the lives of some patients infected with COVID-19. PF is a multicellular pathological process, including the initial injuries of epithelial cells, recruitment of inflammatory cells, epithelial-mesenchymal transition, activation and differentiation of fibroblasts, etc. TGF-[Formula: see text]1 acts as a key effect factor that participates in these cellular processes of PF. Recently, much attention was paid to inhibiting TGF-[Formula: see text]1 mediated cell processes in the treatment of PF with Chinese herbal medicines (CHM), an important part of traditional Chinese medicine. Here, this review first summarized the effects of TGF-[Formula: see text]1 in different cellular processes of PF. Then, this review summarized the recent research on CHM (compounds, multi-components, single medicines and prescriptions) to directly and/or indirectly inhibit TGF-[Formula: see text]1 signaling (TLRs, PPARs, micrRNA, etc.) in PF. Most of the research focused on CHM natural compounds, including but not limited to alkaloids, flavonoids, phenols and terpenes. After review, the research perspectives of CHM on TGF-[Formula: see text]1 inhibition in PF were further discussed. This review hopes that revealing the inhibiting effects of CHM on TGF-[Formula: see text]1-mediated cellular processes of PF can promote CHM to be better understood and utilized, thus transforming the therapeutic activities of CHM into practice.


Тема - темы
Cell Physiological Phenomena/drug effects , Drugs, Chinese Herbal/therapeutic use , Pulmonary Fibrosis/drug therapy , Signal Transduction/drug effects , Transforming Growth Factor beta1/antagonists & inhibitors , COVID-19/complications , COVID-19/metabolism , COVID-19/virology , Humans , Medicine, Chinese Traditional/methods , Phytotherapy/methods , Pulmonary Fibrosis/complications , Pulmonary Fibrosis/metabolism , SARS-CoV-2/physiology , Transforming Growth Factor beta1/metabolism
11.
Medicine (Baltimore) ; 100(51): e28282, 2021 Dec 23.
Статья в английский | MEDLINE | ID: covidwho-1595309

Реферат

BACKGROUND: Novel coronavirus disease (COVID-19) is a kind of pulmonary inflammation induced by New Coronavirus. It seriously threatens people's health and safety. Clinical studies have found that some patients have different degrees of inflammation after discharge from hospital, especially in patients with severe inflammatory lung fibrosis. Early combination of Chinese medicine and modern medicine has important clinical significance. There are still many deficiencies in the current research. We studied the effectiveness of the combination of traditional Chinese medicine and modern medicine in the treatment of pulmonary fibrosis caused by COVID-19, and proposed a network meta-analysis (NMA) scheme. METHODS: According to the search strategy, we will search Chinese and English databases to collect all randomized controlled trials of traditional Chinese medicine combined with modern drugs or only using traditional Chinese medicine for new coronavirus-19-induced pulmonary fibrosis between December 1, 2019 and November 15, 2021. First, the literature was screened according to the eligibility criteria, endnotex9 was used to manage the literature, and the Cochrane Collaboration's tool was used to assess the quality of the included literature. Revman 5.3, Stata 14.2, and gemtc14.3 meta-analysis software was then used for data processing and analysis, and the grading of recommendations assessment will be used to develop and evaluate a hierarchy for classifying the quality of evidence for NMA. RESULTS: Through the analysis, the ranking of efficacy and safety of various treatments for pulmonary fibrosis caused by COVID-19 will be drawn, thus providing stronger evidence support for the choice of clinical treatment methods. CONCLUSION: Traditional Chinese medicine (TCM) combined with modern drugs has played a positive role in the treatment of pulmonary fibrosis caused by COVID-19, and this study may provide more references for the clinical medication of pulmonary fibrosis caused by COVID-19. INPLASY REGISTRATION NUMBER: INPLASY2021110061.


Тема - темы
COVID-19 , Drugs, Chinese Herbal , Pulmonary Fibrosis , Bayes Theorem , COVID-19/drug therapy , Drugs, Chinese Herbal/therapeutic use , Humans , Medicine, Chinese Traditional , Meta-Analysis as Topic , Network Meta-Analysis , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/virology , Randomized Controlled Trials as Topic , Treatment Outcome
12.
Int J Mol Sci ; 23(1)2021 Dec 24.
Статья в английский | MEDLINE | ID: covidwho-1580700

Реферат

Acute respiratory distress syndrome (ARDS) followed by repair with lung remodeling is observed in COVID-19. These findings can lead to pulmonary terminal fibrosis, a form of irreversible sequelae. There is evidence that TGF-ß is intimately involved in the fibrogenic process. When activated, TGF-ß promotes the differentiation of fibroblasts into myofibroblasts and regulates the remodeling of the extracellular matrix (ECM). In this sense, the present study evaluated the histopathological features and immunohistochemical biomarkers (ACE-2, AKT-1, Caveolin-1, CD44v6, IL-4, MMP-9, α-SMA, Sphingosine-1, and TGF-ß1 tissue expression) involved in the TGF-ß1 signaling pathways and pulmonary fibrosis. The study consisted of 24 paraffin lung samples from patients who died of COVID-19 (COVID-19 group), compared to 10 lung samples from patients who died of H1N1pdm09 (H1N1 group) and 11 lung samples from patients who died of different causes, with no lung injury (CONTROL group). In addition to the presence of alveolar septal fibrosis, diffuse alveolar damage (DAD) was found to be significantly increased in the COVID-19 group, associated with a higher density of Collagen I (mature) and III (immature). There was also a significant increase observed in the immunoexpression of tissue biomarkers ACE-2, AKT-1, CD44v6, IL-4, MMP-9, α-SMA, Sphingosine-1, and TGF-ß1 in the COVID-19 group. A significantly lower expression of Caveolin-1 was also found in this group. The results suggest the participation of TGF-ß pathways in the development process of pulmonary fibrosis. Thus, it would be plausible to consider therapy with TGF-ß inhibitors in those patients recovered from COVID-19 to mitigate a possible development of pulmonary fibrosis and its consequences for post-COVID-19 life quality.


Тема - темы
COVID-19/metabolism , Pulmonary Fibrosis/metabolism , Signal Transduction , Transforming Growth Factor beta/metabolism , Actins/metabolism , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/complications , COVID-19/drug therapy , COVID-19/pathology , Caveolin 1/metabolism , Collagen Type I/metabolism , Collagen Type III/metabolism , Female , Humans , Hyaluronan Receptors/metabolism , Immunohistochemistry , Influenza A Virus, H1N1 Subtype/metabolism , Influenza, Human/metabolism , Influenza, Human/pathology , Interleukin-4/metabolism , Male , Matrix Metalloproteinase 9/metabolism , Middle Aged , Proto-Oncogene Proteins c-akt/metabolism , Pulmonary Fibrosis/complications , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/pathology , Retrospective Studies , Transforming Growth Factor beta1/metabolism
13.
Expert Opin Investig Drugs ; 30(12): 1183-1195, 2021 Dec.
Статья в английский | MEDLINE | ID: covidwho-1541410

Реферат

INTRODUCTION: Lung injury in severe COVID-19 pneumonia can rapidly evolve to established pulmonary fibrosis, with prognostic implications in the acute phase of the disease and long-lasting impact on the quality of life of COVID-19 survivors. This is an emerging medical need, and it has been hypothesized that antifibrotic treatments could have a role in ameliorating the fibrotic process in the lungs of these patients. AREAS COVERED: The safety and efficacy of available antifibrotic drugs (nintedanib and pirfenidone) and novel promising agents are being assessed in several ongoing clinical trials that were performed either in critically ill patients admitted to intensive care, or in discharged patients presenting fibrotic sequalae from COVID-19. Literature search was performed using Medline and Clinicaltrials.org databases (2001-2021). EXPERT OPINION: Despite the strong rationale support the use of antifibrotic therapies in COVID-related fibrosis, there are several uncertainties regarding the timing for their introduction and the real risks/benefits ratio of antifibrotic treatment in the acute and the chronic phases of the disease. The findings of ongoing clinical trials and the long-term observation of longitudinal cohorts will eventually clarify the best management approach for these patients.


Тема - темы
/therapeutic use , COVID-19/complications , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/etiology , Animals , Critical Illness , Humans , Indoles/therapeutic use , Pyridones
14.
Eur J Clin Pharmacol ; 76(11): 1615-1618, 2020 Nov.
Статья в английский | MEDLINE | ID: covidwho-1384377

Реферат

AIM: SARS-CoV-2 infection has been divided by scientific opinion into three phases: the first as asymptomatic or slightly symptomatic and the second and the third with greater severity, characterized by a hyperinflammatory and fibrotic state, responsible for lung lesions, in some cases fatal. The development of antiviral drugs directed against SARS-CoV-2 and effective vaccines is progressing; meanwhile, the best pharmacological objective is related to the management of all the complications caused by this viral infection, mainly controlling the inflammatory and fibrotic state and preventing the infection from moving into the most serious phases. SUBJECT AND METHOD: Describe the scientific rationale related to the use of an antifibrotic therapy with pirfenidone, as monotherapy and/or in combination with anti-inflammatory drugs to manage and control complications of SARS-CoV-2 infection. RESULTS: Based on the scientific literature and epidemiological results and considering the pathophysiological, biological, and molecular characteristics of SARS-CoV-2, an antifibrotic drug such as pirfenidone as monotherapy or in combination with anti-inflammatory drugs can be (acting early, at the right doses and at the right time) therapeutically effective to avoid serious complications during viral infection. The same approach can also be effective as postinfection therapy in patients with residual pulmonary fibrotic damage. Management of inflammation and fibrotic status with a combination therapy of pirfenidone and IL-6 or IL-1 inhibitors could represent a pharmacological synergy with added value. CONCLUSION: In this article, we consider the role of antifibrotic therapy with pirfenidone in patients with SARS-CoV-2 infection on going or in the stage of postinfection with pulmonary fibrotic consequences. The scientific rationale for its use is also described.


Тема - темы
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/etiology , Pyridones/therapeutic use , Betacoronavirus , COVID-19 , Drug Therapy, Combination , Humans , Inflammation/drug therapy , Interleukin-1/antagonists & inhibitors , Interleukin-6/antagonists & inhibitors , Pandemics , SARS-CoV-2
15.
Int J Mol Sci ; 22(17)2021 Aug 24.
Статья в английский | MEDLINE | ID: covidwho-1374422

Реферат

The lungs play a very important role in the human respiratory system. However, many factors can destroy the structure of the lung, causing several lung diseases and, often, serious damage to people's health. Nerve growth factor (NGF) is a polypeptide which is widely expressed in lung tissues. Under different microenvironments, NGF participates in the occurrence and development of lung diseases by changing protein expression levels and mediating cell function. In this review, we summarize the functions of NGF as well as some potential underlying mechanisms in pulmonary fibrosis (PF), coronavirus disease 2019 (COVID-19), pulmonary hypertension (PH), asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. Furthermore, we highlight that anti-NGF may be used in future therapeutic strategies.


Тема - темы
Airway Remodeling/drug effects , Lung/pathology , Nerve Growth Factor/antagonists & inhibitors , Signal Transduction/drug effects , Asthma/drug therapy , Asthma/pathology , COVID-19/drug therapy , COVID-19/pathology , Humans , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/pathology , Lung/drug effects , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Molecular Targeted Therapy/methods , Nerve Growth Factor/metabolism , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/pathology , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/pathology
16.
Carbohydr Polym ; 273: 118567, 2021 Dec 01.
Статья в английский | MEDLINE | ID: covidwho-1363900

Реферат

Diffuse alveolar injury and pulmonary fibrosis (PF) are the main causes of death of Covid-19 cases. In this study a low molecular weight fucoidan (LMWF) with unique structural was obtained from Laminaria japonica, and its anti- PF and anti-epithelial-mesenchymal transition (EMT) bioactivity were investigated both in vivo and in vitro. After LWMF treatment the fibrosis and inflammatory factors stimulated by Bleomycin (BLM) were in lung tissue. Immunohistochemical and Western-blot results found the expression of COL2A1, ß-catenin, TGF-ß, TNF-α and IL-6 were declined in mice lung tissue. Besides, the phosphorylation of PI3K and Akt were inhibited by LMWF. In addition, the progression of EMT induced by TGF-ß1 was inhibited by LMWF through down-regulated both TGF-ß/Smad and PI3K/AKT signaling pathways. These data indicate that unique LMWF can protect the lung from fibrosis by weakening the process of inflammation and EMT, and it is a promising therapeutic option for the treatment of PF.


Тема - темы
COVID-19/complications , Epithelial-Mesenchymal Transition/drug effects , Polysaccharides/administration & dosage , Polysaccharides/chemistry , Pulmonary Fibrosis/complications , Pulmonary Fibrosis/drug therapy , SARS-CoV-2 , A549 Cells , Animals , Bleomycin/adverse effects , COVID-19/virology , Cell Survival/drug effects , Cytokines/antagonists & inhibitors , Cytokines/metabolism , Cytokines/pharmacology , Disease Models, Animal , Humans , Inflammation/drug therapy , Lung/immunology , Male , Mice , Mice, Inbred C57BL , Molecular Weight , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/mortality , Signal Transduction/drug effects
17.
Int J Mol Sci ; 22(8)2021 Apr 17.
Статья в английский | MEDLINE | ID: covidwho-1298166

Реферат

The virus responsible for the current COVID-19 pandemic is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): a new virus with high infectivity and moderate mortality. The major clinical manifestation of COVID-19 is interstitial pneumonia, which may progress to acute respiratory distress syndrome (ARDS). However, the disease causes a potent systemic hyperin-flammatory response, i.e., a cytokine storm or macrophage activation syndrome (MAS), which is associated with thrombotic complications. The complexity of the disease requires appropriate intensive treatment. One of promising treatment is statin administration, these being 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors that exert pleiotropic anti-inflammatory effects. Recent studies indicate that statin therapy is associated with decreased mortality in COVID-19, which may be caused by direct and indirect mechanisms. According to literature data, statins can limit SARS-CoV-2 cell entry and replication by inhibiting the main protease (Mpro) and RNA-dependent RNA polymerase (RdRp). The cytokine storm can be ameliorated by lowering serum IL-6 levels; this can be achieved by inhibiting Toll-like receptor 4 (TLR4) and modulating macrophage activity. Statins can also reduce the complications of COVID-19, such as thrombosis and pulmonary fibrosis, by reducing serum PAI-1 levels, attenuating TGF-ß and VEGF in lung tissue, and improving endothelial function. Despite these benefits, statin therapy may have side effects that should be considered, such as elevated creatinine kinase (CK), liver enzyme and serum glucose levels, which are already elevated in severe COVID-19 infection. The present study analyzes the latest findings regarding the benefits and limitations of statin therapy in patients with COVID-19.


Тема - темы
COVID-19/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Animals , COVID-19/complications , Endothelium/drug effects , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Inflammation/complications , Inflammation/drug therapy , Lipid Metabolism/drug effects , Macrophage Activation/drug effects , Pulmonary Fibrosis/complications , Pulmonary Fibrosis/drug therapy , SARS-CoV-2/drug effects , Thrombosis/complications , Thrombosis/drug therapy
18.
Minerva Med ; 113(1): 135-140, 2022 Feb.
Статья в английский | MEDLINE | ID: covidwho-1285637

Реферат

BACKGROUND: The aim of this study was to evaluate the combination of Pycnogenol® (150 mg/day) (Horphag Research, London, UK) and Centella asiatica (Centellicum® 3×225 mg/day; Horphag Research) (PY-CE) for 8 months in subjects with sequelae of idiopathic interstitial pneumonia (IIP). Recently, post-COVID-19 lung disease is emerging with large numbers of patients left with chronic lung conditions. Considering the antifibrotic activity of the combination PY-CE, we also tested this supplementary management in post-COVID-19 lung patients. METHODS: Nineteen subjects with idiopathic interstitial pneumonia (IIP) were included in the study. High Resolution CT scans at inclusion confirmed the presence of lung fibrosis: 10 patients were treated with the Pycnogenol® Centellicum® combination and 9 subjects with standard management (SM) served as controls. Oxidative stress that was very high in all subjects at inclusion, decreased significantly in the supplement group (P<0.05). The Karnofsky Performance Scale Index significantly improved in the supplement group in comparison with controls (P<0.05). The symptoms (fatigue, muscular pain, dyspnea) were significantly lower after 8 months in supplemented patients (P<0.05) as compared with controls. RESULTS: At the end of the study, the small cystic lesions (honeycombing) and traction bronchiectasis were stable or in partial regression in 4 subjects in the supplemented group (vs. none in the control group) with a significant improvement in tissue edema in the supplemented subjects. On ultrasound lung scans the white (more echogenic) fibrotic component at inclusion was 18.5±2.2% in the images in controls vs. 19.4±2.7% in the supplement group. At the end of the study, there was no improvement in controls (18.9±2.5%) vs. a significant improvement in supplemented subjects (16.2±2.1%; P<0.05). In addition, 18 subjects with post-COVID-19 lung disease were included in the study; 10 patients were treated with the Pycnogenol® Centellicum® combination and evaluated after 4 weeks; 8 patients served as controls. Preliminary results show that symptoms associated with post-COVID-19 lung disease after 4 weeks were significantly improved with the supplement combination (P<0.05). Oxidative stress and the Karnofsky Performance Scale Index were significantly improved in the supplements group as compared with controls (P<0.05). CONCLUSIONS: According to these observations, Pycnogenol® controls and decreases edema and Centellicum® by modulating the apposition of collagen, slows down the development of irregular cicatrization, the keloidal scarring and fibrosis. More time is needed to evaluate this effect in a larger number of post-COVID-19 patients with lung disease. This disease has affected millions of subjects worldwide, leaving severe consequences. Pycnogenol® and Centellicum® may improve the residual clinical picture in post-COVID-19 lung disease (PCL) patients and may reduce the number of subjects evolving into lung fibrosis. The evolution from edema to fibrosis seems to be slower or attenuated with this supplement combination both in Idiopathic pulmonary fibrosis (IPF) and in PCL patients.


Тема - темы
COVID-19 , Pulmonary Fibrosis , COVID-19/complications , COVID-19/drug therapy , Dietary Supplements , Flavonoids/therapeutic use , Humans , Lung/diagnostic imaging , Plant Extracts/therapeutic use , Pulmonary Fibrosis/diagnostic imaging , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/etiology
19.
Am J Pathol ; 191(7): 1193-1208, 2021 07.
Статья в английский | MEDLINE | ID: covidwho-1283899

Реферат

Pulmonary fibrosis (PF) can arise from unknown causes, as in idiopathic PF, or as a consequence of infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current treatments for PF slow, but do not stop, disease progression. We report that treatment with a runt-related transcription factor 1 (RUNX1) inhibitor (Ro24-7429), previously found to be safe, although ineffective, as a Tat inhibitor in patients with HIV, robustly ameliorates lung fibrosis and inflammation in the bleomycin-induced PF mouse model. RUNX1 inhibition blunted fundamental mechanisms downstream pathologic mediators of fibrosis and inflammation, including transforming growth factor-ß1 and tumor necrosis factor-α, in cultured lung epithelial cells, fibroblasts, and vascular endothelial cells, indicating pleiotropic effects. RUNX1 inhibition also reduced the expression of angiotensin-converting enzyme 2 and FES Upstream Region (FURIN), host proteins critical for SARS-CoV-2 infection, in mice and in vitro. A subset of human lungs with SARS-CoV-2 infection overexpress RUNX1. These data suggest that RUNX1 inhibition via repurposing of Ro24-7429 may be beneficial for PF and to battle SARS-CoV-2, by reducing expression of viral mediators and by preventing respiratory complications.


Тема - темы
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Core Binding Factor Alpha 2 Subunit/antagonists & inhibitors , Furin/metabolism , Lung/drug effects , Pulmonary Fibrosis/drug therapy , Animals , Bleomycin , Cells, Cultured , Disease Models, Animal , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Female , Lung/metabolism , Lung/pathology , Male , Mice , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/pathology , Treatment Outcome
20.
Biomaterials ; 275: 120986, 2021 08.
Статья в английский | MEDLINE | ID: covidwho-1275155

Реферат

Pulmonary fibrosis is an irreparable and life-threatening disease with only limited therapeutic options. The recent outbreak of COVID-19 has caused a sharp rise in the incidence of pulmonary fibrosis owing to SARS-CoV-2 infection-mediated acute respiratory distress syndrome (ARDS). The considerable oxidative damage caused by locally infiltrated immune cells plays a crucial role in ARDS, suggesting the potential use of antioxidative therapeutics. Here, we report the therapeutic potential of nanoparticles derived from the endogenous antioxidant and anti-inflammatory bile acid, bilirubin (BRNPs), in treating pulmonary fibrosis in a bleomycin-induced mouse model of the disease. Our results demonstrate that BRNPs can effectively reduce clinical signs in mice, as shown by histological, disease index evaluations, and detection of biomarkers. Our findings suggest that BRNPs, with their potent antioxidant and anti-inflammatory effects, long blood circulation half-life, and preferential accumulation at the inflamed site, are potentially a viable clinical option for preventing Covid-19 infection-associated pulmonary fibrosis.


Тема - темы
COVID-19 , Pulmonary Fibrosis , Animals , Bilirubin , Humans , Mice , Nanomedicine , Pulmonary Fibrosis/drug therapy , SARS-CoV-2
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