Lung Damage Research Articles

Correlation of the severity of the clinical presentation of SARS-CoV-2 pneumonia with respiratory function parameters in the post-COVID period.

Since COVID-19 first surfaced in 2019, it has seriously threatened public health. The most prevalent symptoms are respiratory ones. This study aimed to present the correlation between the severity of the clinical presentation of the disease and the results of respiratory function tests conducted within 6 months after hospital discharge. This retrospective study included 99 patients with confirmed SARS-CoV-2 virus infection. Of all patients 24.2% had accentuated bronchovascular pattern, 9.1% had unilateral, and 29.3% had bilateral pneumonia. In comparison, 35.4% patients had diffuse changes, which were described as acute respiratory distress syndrome (ARDS) on computed tomography (CT). Patients with unilateral, bilateral pneumonia or diffuse lung damage had significantly lower forced vital capacity (FVC) values. They were treated with non-invasive mechanical ventilation (NIV) or invasive mechanical ventilation (MV) and had lower FVC values (0.039). A negative, weak correlation existed between CT findings during the infection and Diffusing capacity for carbon monoxide (DLCO) measured after the infection (0.003). A negative, weak correlation was found between oxygen therapy, the use of NIV, and MV findings during the infection with DLCO. A negative correlation was noted between leukocyte values during the infection and forced expiratory volume in the first second (FEV1) and FVC after the infection. Patients with COVID-19 infection who need oxygen support and MV continue to suffer from loss of respiratory function after the resolution of COVID-19 infection. These findings highlight the negative predictive value of pulmonary tests in the long-term follow-up for the development of PC-ILD as well as decreased pulmonary capacity.

The management of Pseudomonas aeruginosa respiratory infection in children with cerebral palsy: A narrative review.

Children with cerebral palsy have increased respiratory morbidity and mortality. Infection with Pseudomonas aeruginosa (PA) is associated with poorer outcomes, yet there are no formal guidelines to inform treatment of respiratory infection in children with cerebral palsy. This review explores the existing literature regarding management of PA-infection in children with cerebral palsy, with the aim of synthesising clinical recommendations and identifying gaps in current understanding. Medline (Ovid), PubMed and Embase were searched using keywords. Full-text articles involving the paediatric population and antimicrobial therapy were included. There was no limit on date of publication. Four retrospective case series were identified. Respiratory microbiology, in samples collected from a range of sites along the respiratory tract, was reported in three studies. Patients who received PA-specific antibiotics clinically improved. Two studies suggest that the use of suppressive inhaled anti-pseudomonal therapy may improve respiratory morbidity in the chronic setting. There is minimal evidence to guide management of PA respiratory infection in children with cerebral palsy. Children with cerebral palsy are at risk of developing bronchiectasis, so in the absence of high-quality evidence, management should be informed by extrapolating from the non-cystic fibrosis bronchiectasis guidelines. Further research examining surveillance and management of PA-infection in this population is required given that early intervention may prevent irreversible lung damage.

Lung damage in SARS-CoV-2 patients: An autopsy study in the era of vaccination.

The contribution of SARS-CoV-2 infection on lung damage and the effect of vaccination on either containing the number of deaths or mitigating lung damage has not been systematically investigated. Post-mortem analysis was performed among consecutive in-patients with COVID-19 deceased in the Province of Trieste (2020-2022). The outcomes of the study were (i) rates of in-hospital mortality, (ii) contribution of COVID-19 to death, (iii) histological extent of lung injury and (iv) impact of vaccination. A total of 1038 consecutive hospitalized patients who died with SARS-CoV-2 infection were autopsied and deep histological analysis of the lungs was performed in a randomly selected sample of 508 cases. Among them, SARS-CoV-2 infection was (a) the cause of death (n = 90), (b) contributing to death (n = 304) and (c) an accompanying feature (n = 114). The incidence of SARS-CoV-2 infection as the primary cause of mortality decreased over time (23.8% in 2020, 20.9% in 2021 and 7.9% in 2022). On multivariable analysis, vaccination (any dose) was independently associated with lower rates of death related to SARS-CoV-2 infection (HR .15, p < .001), after adjusting for other independent predictors. A total of 172 patients were vaccinated at least with two doses at the time of death: 93% triple-vaccinated, 7% double-vaccinated. On histological analysis, vaccinated patients had a greater frequency of pneumonia severity score 0 and 1 (20.3% vs. 5.4% and 20.9% vs. 7.7%, p < .001, respectively), and a substantially lower proportion of pneumonia severity score 3 (26.2% vs. 55.1%, p < .001) compared to unvaccinated patients. COVID-19 vaccination has substantially reduced rates of death related to SARS-CoV-2 infection over time and may have the ability to mitigate lung damage.

An amphiregulin reporter mouse enables transcriptional and clonal expansion analysis of reparative lung Treg cells.

Regulatory T (Treg) cells are known to play critical roles in tissue repair via provision of growth factors such as amphiregulin (Areg). Areg-producing Treg cells have previously been difficult to study because of an inability to isolate live Areg-producing cells. In this report, we created a novel reporter mouse to detect Areg expression in live cells ( Areg Thy1.1 ). We employed influenza A and bleomycin models of lung damage to sort Areg-producing and -non-producing Treg cells for transcriptomic analyses. Single cell RNA-seq revealed distinct subpopulations of Treg cells and allowed transcriptomic comparisons of damage-induced populations. Single cell TCR sequencing showed that Treg cell clonal expansion is biased towards Areg-producing Treg cells, and largely occurs within damage-induced subgroups. Gene module analysis revealed functional divergence of Treg cells into immunosuppression-oriented and tissue repair-oriented groups, leading to identification of candidate receptors for induction of repair activity in Treg cells. We tested these using an ex vivo assay for Treg cell-mediated tissue repair, identifying 4-1BB agonism as a novel mechanism for reparative activity induction. Overall, we demonstrate that the Areg Thy1.1 mouse is a promising tool for investigating tissue repair activity in leukocytes.

A network pharmacology approach-based decoding of Resveratrol's anti-fibrotic mechanisms

BackgroundInhalation of crystalline silica (CS) frequently leads to chronic lung inflammation and pulmonary fibrosis (PF), a condition with limited effective treatments. Resveratrol (Res) has demonstrated potential in PF treatment; however, its underlying mechanisms remain incompletely elucidated. PurposeThis study represents the first comprehensive attempt to uncover the novel mechanisms underlying Res's anti-fibrotic effects against PF through an innovative, integrated approach combining network pharmacology and experimental validation. MethodsWe employed network pharmacology to investigate the holistic pharmacological mechanism of Res, then validated the predicted pharmacological effects using in vivo and in vitro studies. ResultsIn total, 216 genes were identified to be simultaneously associated with PF and Res. An integrated bioinformatics analysis implicated a crucial role of the autophagy signaling pathway in dominating PF, with AMPK and mTOR showing high docking scores. Animal studies revealed that Res significantly alleviated silica-induced lung damage in silicotic mice, with decreased collagen I (Col-I) levels and reduced expression of vimentin and α-SMA. In-depth investigation demonstrated that Res modulated CS-dysregulated autophagy by targeting the AMPK/mTOR pathway. in vitro, Res treatment significantly reduced lactate dehydrogenase (LDH), TNF-α, and TGF-β levels and improved cell viability of Raw264.7 cells post-CS exposure. Notably, Res was demonstrated to suppress fibroblast-to-myofibroblast transition via mediating macrophage autophagy through the AMPK/mTOR pathway. ConclusionRes can alleviate CS-induced PF by targeting AMPK in the autophagy signaling pathway, which sheds light on Res' therapeutic potential in treating PF.

Mutating a flexible region of the RSV F protein can stabilize the prefusion conformation.

The respiratory syncytial virus (RSV) fusion (F) glycoprotein is highly immunogenic in its prefusion (pre-F) conformation. However, the protein is unstable, and its conformation must be stabilized for it to function effectively as an immunogen in vaccines. We present a mutagenesis strategy to arrest the RSV F protein in its pre-F state by blocking localized changes in protein structure that accompany large-scale conformational rearrangements. We generated a series of mutants and screened them in vitro to assess their potential for forming a stable pre-F. In animals, the immunogenicity of a representative mutant F protein, with a conformation confirmed by cryo-electron microscopy, elicited levels of neutralizing antibodies and protection against RSV-induced lung damage that were comparable to those of DS-Cav1, a pre-F used in a licensed vaccine.

Relationship between fat embolism and endothelial glycocalyx

Fat embolism (FE) is acknowledged as one of the significant causes of sudden death following traumatic injury. To clarify the relevance of vascular endothelial glycocalyx (EGC) damage and FE, temporal changes in the mRNA levels of inflammatory cytokines associated with EGC components were investigated in an experimental fat embolization rat model. Nine-week-old rats were used as FE models through triolein injection (TO) and femoral fracture (FX), and physiological saline was administered to the control group. RT-qPCR and fat staining were performed. The target genes were Il6, Il10, Tnf, Elane, Sdc1, Sdcbp, Vcan, Hyal1, Fn1, and CD14. Notably, FE was detected in 100% and 5.6% of the TO and FX groups, respectively, using fat staining. Bimodal peaks in the mRNA expression levels of Sdc1, Tnf, Elane, IL6, and IL10 were observed 4 and 20 h after treatment in both groups. In the TO group, mRNA expression peaked at 4 h and then declined to the lowest level at 16 h. The incidence of fat emboli due to trauma was consistent with that reported in previous studies. Bimodal mRNA peaks may correspond to FE progression, in which physical obstructions are followed by biochemical reactions. The fluctuation in Sdc1 expression suggests that the initial peak resulted from physical EGC damage. The subsequent peak could be because of EGC damage caused by the secretion of inflammatory cytokines induced by oleic acid from lipid droplet decomposition. These results suggest that EGC disorders caused by lipid droplets may induce lung damage during FE.

Clinical and immunological characteristics of post-covid patients with infectious immunopathology syndrome

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has caused global morbidity and high mortality worldwide. Today it is known that, despite recovery from COVID-19, confirmed by both laboratory and instrumental diagnostic methods, many patients, regardless of the severity of the disease, suffer from a significant deterioration in health and increased exacerbations of chronic diseases. During examinations by attending physicians, they note fatigue, an increase in cases of acute respiratory viral infections per year, an increase in relapses of skin diseases such as furunculosis, pyoderma, exacerbation of pulmonary pathologies, pathologies of the urinary tract of inflammatory origin, as well as chronic infectious diseases such as herpesvirus and human papillomavirus infections, which occur for the first time or are characterized by frequent relapses no less than six months after recovery from acute COVID-19. Such persistent post-infectious consequences are known as post-COVID syndrome. SARS-CoV-2 infection is accompanied by damage to both the acquired and innate immune systems. In previous work, we determined the role of B cells, cytotoxic T lymphocytes, natural killer cells and the regulatory properties of CD46, as well as its involvement in the processes of viral entry into the cell. In this study, we studied the relationship of immune disorders of these factors of innate and acquired immunity with the clinical manifestations of post-COVID infectious syndrome in this category of patients and the severity of lung damage in these patients during the acute period of COVID-19. The results of the study showed that in some patients more than six months after suffering from COVID-19, the following was revealed: in patients who had a coronavirus infection without lung damage, no violations of the innate and acquired parts of the immune system were detected. In addition, significant differences were identified between clinical manifestations of diseases with increasing cases of relapses or newly identified after clinical recovery from an acute COVID-19 infection, depending on the phenotype of immune status disorders.

The role of coronavirus infection in lung injury, which contributes to the occurrence of complicated course of community-acquired pneumonia

Annotation. The review article focuses on the role of coronavirus infection in lung damage, which contributes to the complicated course of community-acquired pneumonia. Based on the scientometric databases Web of science, Scopus, PubMed, a retrospective analysis of the literature on this topic for 2013-2023 was conducted. 32 sources were selected after reviewing the abstracts of the articles and reading their full text. The results of the search indicate that most people infected with SARS-CoV-2 do not develop severe illness, and the infection is likely to be limited to the upper respiratory tract. However, in some people, infection with the virus leads to severe pneumonia dominated by immunopathology, probably caused by lower respiratory tract infection. Alveolar damage can be a direct consequence of cell infection or an indirect consequence caused by local inflammatory reactions. People with severe COVID-19 often have a tendency to have a delayed immune response. Inflammation and coagulation further exacerbate pro-inflammatory and/or profibrotic reactions, which contributes to the development of complications. Uncontrolled inflammation ultimately leads to severe immunopathology characteristic of COVID-19. In this regard, understanding the pathogenesis of SARS-CoV-2 infection and how it contributes to critical illness and its complications may help to improve risk allocation and develop targeted therapies to reduce the acute and long-term consequences of this disease.

Postnatal hypoxic preconditioning attenuates lung damage from hyperoxia in newborn mice.

Preterm infants frequently require oxygen supplementation at birth. However, preterm lung is especially sensible to structural and functional damage caused by oxygen free radicals. The adaptive mechanisms implied in the fetal-neonatal transition from a lower to a higher oxygen environment were evaluated in a murine model using a custom-designed oxy-chamber. Pregnant mice were randomly assigned to deliver in 14% (hypoxic preconditioning group) or 21% (normoxic group) oxygen environment. Eight hours after birth FiO2 was increased to 100% for 60 min and then switched to 21% in both groups. A control group remained in 21% oxygen throughout the study. Mice in the normoxic group exhibited thinning of the alveolar septa, increased cell death, increased vascular damage, and decreased synthesis of pulmonary surfactant. However, lung histology, lamellar bodies microstructure, and surfactant integrity were preserved in the hypoxic preconditioning group after the hyperoxic insult. Postnatal hyperoxia has detrimental effects on lung structure and function when preceded by normoxia compared to controls. However, postnatal hypoxic preconditioning mitigates lung damage caused by a hyperoxic insult. Hypoxic preconditioning, implemented shortly after birth mitigates lung damage caused by postnatal supplemental oxygenation. The study introduces an experimental mice model to investigate the effects of hypoxic preconditioning and its effects on lung development. This model enables researchers to delve into the intricate processes involved in postnatal lung maturation. Our findings suggest that hypoxic preconditioning may reduce lung parenchymal damage and increase pulmonary surfactant synthesis in reoxygenation strategies during postnatal care.

BCAP31 Alleviates Lipopolysaccharide-Mediated Acute Lung Injury via Induction of PINK1/Parkin in Alveolar Epithelial Type II Cell.

Background: B-cell receptor-associated protein 31 (BCAP31) has protective effects against alveolar epithelial type II cells (AECII) damage by inhibiting mitochondrial injury in acute lung injury (ALI) induced by lipopolysaccharide (LPS), whereas the precise mechanism is still unclear. It is known that PTEN-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy can remove damaged mitochondria selectively, which may be involved in BCAP31 protection against mitochondrial injury. Methods: In the current study, ALI mice models were established by using surfactant protein C (Sftpc)-BCAP31 transgenic mice (BCAP31TG mice) and AECII-specific BCAP31 knockout mice (BCAP31CKO mice) treated with LPS. Results: BCAP31 expression in lung tissue and AECII were inhibited in ALI mice. Under LPS challenge, lower level of BCAP31 was found to correlate positively with pathological injury of the lung, respiratory dysfunction, mortality rates, inflammation response, and AECII damage. Further study showed that down-regulation of BCAP31 induced decreased phosphorylation of PINK1 via reduced binding to PINK1, thereby restraining PINK1/Parkin-mediated mitophagy. Down-regulation of mitophagy promoted mitochondrial injury, as shown by the increase in mitochondrial permeability transition pore opening rate, together with enhanced mitochondrial reactive oxygen species (mROS), which were accompanied by increased cellular apoptosis and reactive oxygen species (ROS). The increased cellular ROS contributed to the inflammatory response via activation of nuclear factor κB (NF-κB). In contrast, BCAP31 overexpression promoted phosphorylation of PINK1 and PINK1/Parkin-mediated mitophagy, thus blocking the mROS/ROS/NF-κB pathway, favoring a protective condition that ultimately led to the inhibition of AECII apoptosis and inflammatory response in LPS-induced ALI. Conclusion: Ultimately, BCAP31 alleviated ALI by activating PINK1/Parkin-mediated mitophagy and blocking the mROS/ROS/NF-κB pathway in AECII.

Collagen-V and K-α-1 Tubulin Antibodies as Potential Markers of Unsuspected GERD-Related Lung Damage: Insights from a Cross-Sectional Analysis

PurposeOur group has proposed that aspiration of gastric contents leads to exposure of normally sequestered lung self-antigens (SAgs), specifically collagen-V (Col-V) and K-α-1-tubulin (Kα1T), which elicits an immune response characterized by increasing concentrations of self-antibodies (SAbs) anti-Col-V and anti-Kα1T. We sought to establish the point prevalence of abnormally elevated concentrations of SAbs among patients with pathological gastroesophageal reflux disease (GERD) and/or hiatal hernia undergoing antireflux surgery (ARS).MethodsFor this cross-sectional study, we retrieved a plasma aliquot from the Norton Thoracic Institute BioBank from blood samples that were taken preoperatively from patients who underwent ARS between November 2019 and August 2022. Enzyme-linked immunosorbent assays were employed to detect and quantify anti-Col-V and anti-Kα1T.ResultsSamples from 43 patients (females, n = 34 [79.1%]; mean age, 62 ± 12 years; and mean BMI, 30.5 ± 7 kg/m2) were analyzed. Before ARS, 28 (65.1%, CI95: 50.3–80.0%) patients had abnormally elevated concentrations of anti-Col-V and 19 (44.2%, CI95: 28.7–59.7%) had elevated concentrations of circulating anti-Kα1T. Overall, 13 patients (30.2%) had low (i.e., normal) concentrations of both SAbs, 13 (30.2%) were positive only for one, and 17 (39.5%) were positive for both SAbs.ConclusionA relative high point prevalence of abnormally elevated circulating SAbs (i.e., anti-Col-V and/or anti-Kα1T) before ARS was found. This result suggests clinically unsuspected pulmonary parenchymal injury secondary to GERD-related aspiration. Further studies are required to confirm this hypothesis and to identify alternative non-invasive early biomarkers of GERD-related lung damage.

Taurochenodeoxycholic acid ameliorates the Staphylococcus aureus infection-induced acute lung injury through toll-like receptor 2 in mice

Acute lung injury (ALI) is a significant clinical problem associated with high morbidity and mortality. Inflammation induced by gram-positive bacterial pathogens, specifically Staphylococcus aureus (S. aureus), plays a major role in ALI development and other infectious diseases. Taurochenodeoxycholic acid (TCDCA) exhibits diverse biological activities and pharmacological effects. Nevertheless, the potential preventive and therapeutic effects of TCDCA and the underlying mechanism in the ALI induced by S. aureus infection remain poorly understood. Our results showed that the TCDCA (0.1 μg/g) had a beneficial effect on lung damage in mice infected with S. aureus. Specifically, TCDCA could lead to a reduction in pulmonary focal or diffuse oedema and a decrease in the infiltration of neutrophils in the S. aureus-infected lungs. We observed that TCDCA could significantly down-regulate the expression of HMGB1 in lung from S. aureus-infected mice. Furthermore, TCDCA could attenuate the production of inflammatory mediators in lungs and serum from S. aureus-infected mice. This finding further supported the notion that TCDCA potentially protects against tissue injury. In addition, TCDCA regulated the secretion of the proinflammatory cytokine, the activation of MAPK and NF-κB signaling pathways, and the activation of TLR2 in macrophages. Notably, TCDCA might reduce the secretion levels of inflammatory mediators and lung damage through the TLR2 in S. aureus-infected macrophages or mice. Altogether, TCDCA shows promise as a potential drug for preventing and treating ALI by modulating or inhibiting inflammatory mediators through TLR2.

Analysis of the course and outcomes of COVID-19 at different stages of the pandemic in hemodialysis patients

The purpose of this study was a comparative analysis of the characteristics of the course and outcomes of COVID-19 in HD patients at different stages of the pandemic, focusing on the of the use of immunomodulatory therapy.Materials and methods. The retrospective study included 897 HD patients with COVID-19 (mean age 60.7 years, M 58.5%) who were hospitalized at Moscow City Hospital № 52. Group 1 (n=720) consisted of patients infected between the end of March 2020 and April 2021, group 2 (n=177) included patients hospitalized in May-December 2021. Each of group was divided into 2 subgroups based on treatment approaches. Subgroup 1a (n=231) included patients of the initial period of the pandemic who did not receive adequate immunomodulatory therapy, while Subgroup 1b (n=489) included patients of the late stage, were treated with IL-6 receptor blockers and corticosteroids. In group 2, 108 patients in Subgroup 2a received similar therapy, while 69 patients in Subgroup 2b were treated with neutralizing monoclonal antibodies in the early stages of the disease.Results. Mortality rates in Group 1 and Group 2 was 20.1% and 14.7%, respectively (p&lt;0.09). The incidence of unfavorable outcome was highest in Subgroup 1a and lowest in Subgroup 2b (31.2% vs 5.8%, p&lt;0.01). Mortality in Subgroups 1b and 2a was comparable (14.9% and 20.4%), despite more severe initial lung damage according to CT data in Subgroup 2a. In these patients, immunomodulators was more frequently combined with therapeutic plasma exchange (TPE). Independent risk factors for an unfavorable outcome were the progression of pulmonary pathology, with the transformation of stages CT 1-2 to CT 3-4, and a high comorbidity index.Conclusions. The use of immunomodulatory drugs imprtoved the effectiveness of COVID-19 treatment in patients with CKD5D. In severe cases, the most favorable outcomes were achieved with a combination of immunobiological drugs, corticosteroids, and TPE. An even more significant reduction in mortality was observed following the introduction of neutralizing monoclonal antibodies into clinical practice. Independent predictors of unfavorable outcome of COVID-19 in HD patients were a high comorbidity index and the progression of CT 1-2 into CT 3-4.

The association of radiologic right heart strain indices with the severity of pulmonary parenchymal involvement and prognosis in patients with COVID-19.

It has been demonstrated that an increase in the diameter of the right ventricle or pulmonary artery in COVID-19 patients could be associated with the severity of lung involvement and may lead to unfavorable outcomes, particularly in the presence of pulmonary vascular diseases. This study investigated the relationship between these right heart strain features, the extent of lung involvement, and their prognostic values in patients without vascular comorbidities. This study selected 154 consecutive patients with positive chest computed tomography (CT) findings and no evidence of concurrent pulmonary disease. Clinical characteristics and adverse outcomes in in-hospital settings were collected retrospectively. Diameters of cardiac ventricles and arteries, along with lung opacification scores, were obtained using CT pulmonary angiography (CTPA) findings, and the association of these variables was evaluated. An increase in pulmonary artery (PA) to ascending aorta (AO) diameter ratio and lung parenchymal damage were significantly and positively correlated (P=0.017), but increased right ventricle (RV) to left ventricle (LV) diameter ratio showed no association with the extent of chest opacification (P=0.098). Evaluating the prognostic ability of both ratios using logistic regression and receiver operating characteristic (ROC) analysis proved no significant class separation in regards to predicting adverse outcomes (PA/AO: OR:1.081, P Value:0.638, RV/LV: OR:1.098, P Value:0.344). In COVID-19 patients without vascular comorbidities, a higher PA/AO diameter ratio was significantly associated with increased lung involvement severity on CT imaging but not with adverse in-hospital outcomes. Conversely, an increased RV/LV ratio on CTPA did not correlate significantly with adverse outcomes or the severity of parenchymal lung damage.

Fei-yan-qing-hua decoction exerts an anti-inflammatory role during influenza by inhibiting the infiltration of macrophages and neutrophils through NF-κB and p38 MAPK pathways

Ethnopharmacological relevanceFei-Yan-Qing-Hua decoction (FYQHD) is an empirical formula that has shown clinical success in treating community-acquired pneumonia (CAP) for two decades. Influenza viral infection is a significant trigger for severe pneumonia, yet the role of FYQHD in treating influenza remains unclear. Aim of the studyThis study aimed to assess the potential efficacy of FYQHD in treating influenza viral infection and to elucidate its underlying mechanisms. Materials and methodsThe protective effects of FYQHD against influenza were evaluated through survival assessments and pathological analyses. Transcriptomic analysis was performed to identify the genes and pathways influenced by FYQHD in influenza. The anti-inflammatory effects and molecular mechanisms of FYQHD were studied in macrophages stimulated by Toll-like receptor (TLR) 7 ligation in vitro. The key constituents of FYQHD absorbed in mouse sera were identified using untargeted metabolomics, and the anti-inflammatory activity of some of these compounds in macrophages was evaluated using ELISA. ResultsOur findings demonstrate that FYQHD enhances survival and reduces lung damage in PR8-infected mice, primarily through its anti-inflammatory properties. Lung indexes and organ damage were significantly lower in the PR8 + OSV + FYQHD group compared to the PR8 + OSV group, indicating a potential complementary therapeutic effect of FYQHD and OSV in treating influenza. FYQHD effectively reduced chemokine expression, thereby decreasing the chemotaxis and infiltration of inflammatory monocytes/macrophages and neutrophils in the lungs. The anti-inflammatory effects of FYQHD in macrophages were achieved through the inhibition of NF-κB activation and p38 phosphorylation. The key constituents of FYQHD absorbed in mouse sera were identified, with some, such as wogonin, luteolin, kaempferol, and isorhamnetin, showing anti-inflammatory effects in primary macrophages. ConclusionFYQHD demonstrates protective efficacy against influenza and shows promise as an adjuvant therapeutic agent, particularly when used in combination with antiviral drugs like OSV. The potent anti-inflammatory components within FYQHD provide a basis for further exploration in drug research and development aimed at combating influenza.

Allergic Bronchopulmonary Aspergillosis (ABPA) in the Era of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulators.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity disease caused by Aspergillus fumigatus (Af), prevalent in persons with cystic fibrosis (CF) or asthma. In ABPA, Af proteases drive a T-helper cell-2 (Th2)-mediated allergic immune response leading to inflammation that contributes to permanent lung damage. Corticosteroids and antifungals are the mainstays of therapies for ABPA. However, their long-term use has negative sequelae. The treatment of patients with CF (pwCF) has been revolutionized by the efficacy of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy. Pharmacological improvement in CFTR function with highly effective elexacaftor/tezacaftor/ivacaftor (ETI) provides unprecedented improvements in lung function and other clinical outcomes of pwCF. The mechanism behind the improvement in patient outcomes is a continued topic of investigation as our understanding of the role of CFTR function evolves. As ETI therapy gains traction in CF management, understanding its potential impact on ABPA, especially on the allergic immune response pathways and Af infection becomes increasingly crucial for optimizing patient outcomes. This literature review aims to examine the extent of these findings and expand our understanding of the already published research focusing on the intersection between ABPA therapeutic approaches in CF and the rapid impact of the evolving CFTR modulator landscape. While our literature search yielded limited reports specifically focusing on the role of CFTR modulator therapy on CF-ABPA, findings from epidemiologic and retrospective studies suggest the potential for CFTR modulator therapies to positively influence pulmonary outcomes by addressing the underlying pathophysiology of CF-ABPA, especially by decreasing inflammatory response and Af colonization. Thus, this review highlights the promising scope of CFTR modulator therapy in decreasing the overall prevalence and incidence of CF-ABPA.

Hyaluronan in lung, in plasma as pathogenic and prediction factor of acute respiratory distress syndrome: A systematic review

This investigation aims to study contemporary literature pertaining to the involvement of hyaluronate in the pathogenesis of diverse medical conditions, encompassing coronavirus-induced pulmonary injury, while also exploring its potential utility as a prognostic indicator for assessing the severity of COVID-19. This study conducted a comprehensive examination of hyaluronic acid’s multifaceted role in physiological processes and disease, with a specific focus on its implications in COVID-induced lung damage. The research provided an in-depth analysis of the intricate mechanisms and fundamental patterns governing these biological phenomena, elucidating essential interactions and pathways. Of particular significance in this investigation was the potential diagnostic utility of hyaluronic acid in assessing the severity of acute respiratory distress syndrome (ARDS), including COVID-19. Through a rigorous examination of hyaluronic acid concentration levels, researchers sought to assess its potential as an early prognostic indicator, thereby providing valuable insights for clinical diagnostics. Furthermore, the study explored the therapeutic prospects related to hyaluronic acid, emphasizing its involvement in various pathological processes. It suggested that targeting hyaluronic acid could represent a promising avenue for drug development, potentially leading to the creation of innovative pharmaceutical agents

Effect of Lactiplantibacillus plantarum cell-free culture on bacterial pathogens isolated from cystic fibrosis patients: in vitro and in vivo studies.

This study aimed to investigate the effects of the cell-free supernatant of Lactiplantibacillus plantarum ATCC® 10241TM on the biofilm-forming capacity of Pseudomonas aeruginosa strains isolated from cystic fibrosis (CF) patients. In addition, the study evaluated the in vivo potential of the cell-free supernatant to modulate inflammation and reduce lung damage in mice infected with P. aeruginosa strains or co-challenged with P. aeruginosa and the Streptococcus milleri group (SMG). The results showed that CF-derived P. aeruginosa strains can infect the respiratory tract of adult mice, inducing local inflammation and lung damage. The severity of these infections was exacerbated when P. aeruginosa was co-administered with SMG. Notably, nebulization with the cell-free supernatant of L. plantarum produced beneficial effects, reducing respiratory infection severity and inflammatory responses induced by P. aeruginosa, both alone or in combination with SMG. Reduced bacterial loads and lung damage were observed in supernatant-treated mice compared to controls. Although further mechanistic studies are necessary, the results show that the cell-free supernatant of L. plantarum ATCC® 10241TM is an interesting adjuvant alternative to treat P. aeruginosa respiratory infections and superinfections in CF patients.

Trigonelline alkaloid is effective in preventing doxorubicin-induced lung damage

Background One of the most popular chemotherapy medications is doxorubicin (DOX), however it can have non-negligible damage. When the underlying mechanisms of damage are investigated, the most prominent pathways are oxidative stress, inflammation and apoptosis. Aim We investigated the NF-κB/MAPK inflammatory pathway and cellular apoptosis to determine the efficacy of trigonelline alkaloid (TRIG) in preventing DOX-induced lung injury. Methodology The study consisted of C, TRIG, DOX and TRIG+DOX groups. TRIG and TRIG+DOX groups received 50 mg/kg TRIG for 7 days. On day 8, DOX and TRIG+DOX groups received a single dose of 15 mg/kg DOX. Results Our results showed that apoptosis markers and inflammation were higher in the DOX group. In contrast, TRIG pretreatment partially suppressed apoptosis and decreased inflammation by blocking the activation of the MAPK/NF-κB pathway, lowering IL-6 levels, and protecting the lung from apoptotic cell death. Conclusion Assessing TRIG’s effectiveness in lung tissue injury, this study may be a crucial first step.