Pulmonary Pathology Research Articles

ANTIVIRAL IL-33-STUMULATED GROUP 2 INNATE LYMPHOID CELLS (CD-90 AND CD-117) FROM MOUSE LUNGS

This article represents not only a significant scientific value, but also a great teaching and instruction value for researchers and motivated students to improve the skill spectrum in flow cytometry. This article provides step-by- step procedure description and results based on in vivo studies on murine lung tissue, cell of interest isolation with dual protocols for flow cytometry method as well as IL-33 impact in dynamics. The newly described innate lymphoid cells of group 2 (ILC2) play an important role in type 2 immune reactions, epithelial repair in mucosal tissue and metabolic homeostasis. ILC2 releases large amounts of type 2 cytokines such as interleukin 4 (IL-4), IL-5 and IL-13, which stimulate type 2 immunity, such as protection against worms. However, without strict regulation, the level of ILC2 can cause undesirable type 2 immune pathologies, including allergic inflammation of the respiratory tract, hypersensitivity of the respiratory tract and atopic dermatitis. Viral infections of the respiratory tract, which are typical triggers of type 1 immune reactions, often lead to type 2 pulmonary immune pathologies, such as asthma and its exacerbations. Interestingly, pulmonary virus infections induce the release of IL-33 with subsequent induction of ILC2-mediated type 2 pulmonary immunopathology, which is independent of the adaptive immune system.

Pathologic differences between systemic sclerosis-associated and idiopathic pulmonary arterial hypertension.

Advances in pulmonary arterial hypertension therapies have led to improvements in the quality of life and survival for patients with idiopathic pulmonary arterial hypertension, but these trends have not uniformly translated to patients with systemic sclerosis-associated pulmonary arterial hypertension. In order to better understand the heterogeneity in treatment response and survival, we aimed to examine the histological and immunophenotypic differences between the systemic sclerosis-associated pulmonary arterial hypertension and idiopathic pulmonary arterial hypertension pulmonary vasculopathies. We performed a semi-quantitative lung morphometry-based analysis comparing sections obtained from systemic sclerosis-associated pulmonary arterial hypertension (n = 24), idiopathic pulmonary arterial hypertension (n = 9), and control (n = 13) bio-banked lung tissue specimens. H&E (Hematoxylin and Eosin) and VVG (Verhoeff-Van Gieson)-stained lung sections were analyzed for interstitial and vascular pathology. Immunohistochemistry was used to stain for an array of inflammatory and fibrosis mediators. Baseline demographic and hemodynamic data for each patient were collected via chart review at the time of lung explantation. Plexiform lesions were present in 5/9 (55%) of idiopathic pulmonary arterial hypertension samples, but absent in all systemic sclerosis-associated pulmonary arterial hypertension samples (0/24). Systemic sclerosis-associated pulmonary arterial hypertension lungs demonstrated significantly worse interstitial fibrosis (p = 0.0001) and interstitial cellularity (p = 0.0002) compared to idiopathic pulmonary arterial hypertension lungs. The degree of smooth muscle hypertrophy and pulmonary artery intimal proliferation were not different between systemic sclerosis-associated pulmonary arterial hypertension and idiopathic pulmonary arterial hypertension lungs. Immunohistochemistry analysis revealed that systemic sclerosis-associated pulmonary arterial hypertension lungs exhibited increased interstitial infiltration of CD3 T-cells (p = 0.009), CD20 B-cells (p = 0.01), and CD163 macrophages (p = 0.048) when compared to idiopathic pulmonary arterial hypertension and control lungs. Systemic sclerosis-associated pulmonary arterial hypertension lungs display a distinct pulmonary vascular pathology as well as significant interstitial fibrosis when compared to idiopathic pulmonary arterial hypertension lungs.

Diagnostic comparison of bedside lung ultrasound and chest radiography in the intensive care unit

Bedside lung ultrasound (POCUS) offers advantages over chest X-ray, including better cost-effectiveness for diagnosing certain pulmonary pathologies. This study compares the diagnostic concordance between portable chest X-rays and bedside lung ultrasounds in the intensive care unit (ICU). Adult ICU patients were included. POCUS was performed using the abbreviated BLUE protocol. Diagnostic results from POCUS and chest radiographies were compared using the intensivist clinical diagnosis - based on clinical examinations and lung ultrasounds - as the reference. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the ultrasounds were calculated. A total of 100 patients were included, 71 with pulmonary pathologies. The average time to perform the ultrasound was 308 seconds. Ultrasound identified pathology in 20 patients with a normal chest radiographs. Diagnostic discrepancies occurred in 30 patients, highlighting ultrasound´s superior sensitivity in detecting atelectasis, pleural effusions, and pulmonary edema. Ultrasound demonstrated sensitivity (S) of 85%, specificity (E) of 100%, positive predictive value (PPV) of 100%, and negative predictive value (NPV) of 55%. Lung point-of-care ultrasound at ICU admission detects more pathologies and does not miss significant abnormalities seen on chest X-rays. It also shows good diagnostic accuracy. These findings suggest that pulmonary POCUS, using an abbreviated protocol, could be a viable alternative to chest radiography for initial evaluation and follow-up of pulmonary pathologies in critically ill patients, potentially improving care quality and management.

Brain-wide alterations revealed by spatial transcriptomics and proteomics in COVID-19 infection.

Understanding the pathophysiology of neurological symptoms observed after severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection is essential to optimizing outcomes and therapeutics. To date, small sample sizes and narrow molecular profiling have limited the generalizability of findings. In this study, we profiled multiple cortical and subcortical regions in postmortem brains of patients with coronavirus disease 2019 (COVID-19) and controls with matched pulmonary pathology (total n = 42) using spatial transcriptomics, bulk gene expression and proteomics. We observed a multi-regional antiviral response without direct active SARS-CoV2 infection. We identified dysregulation of mitochondrial and synaptic pathways in deep-layer excitatory neurons and upregulation of neuroinflammation in glia, consistent across both mRNA and protein. Remarkably, these alterations overlapped substantially with changes in age-related neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Our work, combining multiple experimental and analytical methods, demonstrates the brain-wide impact of severe acute/subacute COVID-19, involving both cortical and subcortical regions, shedding light on potential therapeutic targets within pathways typically associated with pathological aging and neurodegeneration.

Comparative assessment of the quality of life in patients with bronchial asthma and chronic obstructive pulmonary disease before and after COVID-19

Objective. To compare the quality of life of patients with bronchial asthma and chronic obstructive pulmonary disease (COPD) before and after COVID-19. Materials and methods. 73 patients diagnosed with bronchial asthma and 78 patients with COPD who were treated at Sechenov University Clinical Hospital №4, participated in the retrospective dynamic comparative study based on the principle «from cause to effect». Assessment of the quality of the patients` life was carried out before and after COVID-19 using a visual analogue scale from 0 to 100 points and the universal EuroQol-5D questionnaire. Mobility, self-care abilities, habitual activity, severity of pain/discomfort, the presence of anxiety/depression in the post-COVID period were assessed. Results. In patients with COPD before COVID-19, the average total score on the visual–analogue scale was 89,5 [83,8; 95], and after COVID-19 it was 70 [64,5; 80] points. In the post-covid period, 91 % of people with COPD noted some mobility limitations, 33.3 % experienced difficulties with self-care, 65.4 % of patients could not engage in habitual activities, 60.3 % suffered pronounced pain or discomfort, and 29.5 % of patients had severe anxiety or depression. In patients with asthma before COVID-19, the average total score was 90 [88,4; 91] points, and after COVID-19 it was 75 [70,2; 80,2]. In the post-ovarian period, mobility limitations were noted by 71.2 % of patients, and 64.4 % had difficulties with taking care of themselves, 54.8 % could not engage in habitual activities. At the same time, 78.1 % of patients experienced pain or discomfort, and 58.9 % had moderate anxiety or depression. Conclusions. COVID-19 has led to a significant decrease in the quality of life in patients with asthma and COPD. This may be associated with a worsening of the course of the disease and increase in the number of exacerbations of these pulmonary pathologies, resulting in significant limitation of mobility, growing pain or discomfort, as well as the occurrence of severe anxiety or depression.

Both chebulagic acid and punicalagin inhibit respiratory syncytial virus entry via multi-targeting glycoprotein and fusion protein.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections, with no currently available small-molecule drugs that are both safe and effective. A major obstacle in antiviral drug development is the rapid emergence of drug-resistant viral strains. Targeting multiple viral compounds may help mitigate the development of resistance. Herein, we conducted a drug screening using the Antiviral Traditional Chinese Medicine Active Compound Library, aiming to identify compounds that simultaneously target the RSV fusion (F) protein, glycoprotein (G), and the host heparan sulfate proteoglycans (HSPGs). From this screening, 10 candidate compounds were identified for their ability to interact with all three targets. Among these 10 candidates, chebulagic acid (CHLA) and punicalagin (PUG) demonstrated the most potent inhibition of RSV replication. In vitro dose-response assays confirmed the antiviral efficacy of CHLA (IC50: 0.07864 µM) and PUG (IC50: 0.08065 µM). Further experiments revealed both CHLA and PUG disrupt RSV attachment and membrane fusion by targeting the RSV-F and G proteins, rather than HSPG. Notably, CHLA and PUG were found to bind to the CX3C motif of the RSV-G protein, with docking assays predicting their binding sites at cysteines 176 and 182. Additionally, CHLA enhanced the conformational stability of the RSV-F protein before fusion. In an in vivo study, both CHLA and PUG were shown to alleviate RSV-induced pulmonary pathology by reducing viral titers, mitigating lung injury, and suppressing the inflammatory responses in the lungs. Our findings suggest that CHLA and PUG hold potential as therapeutic agents for RSV infection.IMPORTANCEA significant challenge in developing anti-respiratory syncytial virus (RSV) agents is the rapid emergence of resistant viral strains. Designing drugs that target multiple viral components can effectively reduce the likelihood of developing resistant strains. In this study, we screened compounds from the Antiviral Traditional Chinese Medicine Active Compound Library, aiming to simultaneously targe the RSV fusion (F) protein, glycoprotein (G), and host heparan sulfate proteoglycans (HSPGs). Our findings revealed that chebulagic acid (CHLA) and punicalagin (PUG) significantly inhibited RSV replication both in vitro and in vivo and interacted with all three targets. Both CHLA and PUG were able to disrupt RSV attachment and membrane fusion. Mechanistically, CHLA and PUG were found to bind to the CX3C motif of the RSV-G protein, with CHLA also enhancing the conformational stability of the RSV-F protein before fusion. In conclusion, our study suggests that CHLA and PUG hold promise as therapeutic agents against RSV infection.

Bullectomy with video-assisted thoracic surgery and minimally invasive repair of pectus excavatum simultaneously

IntroductionPectus excavatum (PE) is the most common chest wall deformity. Surgical treatment with minimally invasive repair (MIRPE) is the most preferred surgical procedure. In the presence of additional pulmonary pathologies, simultaneous surgical procedures have been considered, but there are few cases reported in the literature.Case presentationMIRPE was planned for a 15-year-old male patient due to PE. The day before the surgery, the patient developed sudden onset of shortness of breath. Pneumothorax was observed on the right side in the chest radiograph. Thereupon, the surgery was brought forward. Video-assisted thoracoscopic surgery (VATS) bullectomy was performed in the left lateral decubitus position. MIRPE was then performed through the same incision in the semi-lateral decubitus position. The patient was planned to be discharged on the 7th day, but on the day of discharge, a pneumothorax on the left was observed on the chest x-ray. VATS bullectomy was performed in the left semi-lateral decubitus position. The patient was discharged on postoperative day five.ConclusionSince the long-term results of simultaneous surgical procedures are unknown. With MIRPE, results such as less pain, shorter hospital stays, and earlier involvement in social life are achieved. Keeping in mind that these advantages may be lost with additional procedures, we think that simultaneous procedures should be planned.

Narrative review of chest wall ultrasound: a practical approach.

Traditionally, literature on thoracic ultrasound has focused on the study of pleural and pulmonary pathology. However, given the superficial location of thoracic wall structures, ultrasound proves to be an excellent technique for their examination. This study aims to evaluate the clinical utility of thoracic ultrasound in diagnosing various thoracic wall pathologies and to illustrate the primary diagnoses that can be achieved. We performed a literature search in January 2024 in PubMed and Google Scholar for articles on thoracic ultrasound. Relevant articles were selected and synthesized in a narrative form. Thoracic ultrasound has emerged as a powerful diagnostic tool, especially when combined with a thorough clinical history. It allows for rapid, inexpensive, and safe resolution of a wide range of common clinical uncertainties across all levels of healthcare. In emergency contexts, it excels in the detection of rib fractures, demonstrating superior capability compared to traditional chest X-rays and similar efficacy to computed tomography (CT) scans. Additionally, thoracic ultrasound is highly effective in evaluating tumors, often providing accurate diagnoses without the need for further studies. It also aids in differentiating pathologies that may require more advanced imaging such as CT or magnetic resonance imaging (MRI). Moreover, thoracic ultrasound plays a valuable role in the initial assessment of infectious and degenerative conditions. Thoracic ultrasound is a versatile and efficient diagnostic tool for examining thoracic wall structures. Its applications are particularly valuable in trauma assessment, tumor evaluation, and the differentiation of various pathologies. The rapid, cost-effective, and safe nature of this technique highlights its potential as a primary diagnostic tool in a wide variety of clinical settings.

Pulmonary Aspergillosis: An Observation from a Tertiary Care Hospital of Western Uttar Pradesh

Background: Aspergillus is the most frequently occurring fungal infection in immunocompromised patients with a high mortality rate. Invasive pulmonary aspergillosis is the most serious entity on the spectrum of pulmonary aspergillosis. Limited studies on the occurrence of pulmonary aspergillosis from this geographical area prompted us to carry out this study. Materials and Methods: This hospital-based cross-sectional observational study was carried out in the Postgraduate Department of Microbiology of a tertiary care medical teaching hospital in western Uttar Pradesh for one year. A total of 1032 respiratory samples were subjected for isolation and identification of fungal pathogens by direct microscopic examination (KOH mount) and culture on Sabouraud dextrose agar. Results: The isolation rate of pulmonary aspergilli was 6.97%. The majority of the respiratory samples received were sputum 900 (87.2%) followed by bronchoalveolar lavage fluid 132 (12.7%). The pulmonary pathology was predominantly seen in the age group of 41–50 years (25%). Male patients (69%) were predominant. The majority of the samples (50%) were from the respiratory medicine ward followed by the respiratory medicine ICU (25%). Aspergillus fumigatus (58%) was the predominant species isolated followed by Aspergillus flavus (25%). Conclusion: Isolation of Aspergillus species from patients of pulmonary pathology needs to be correlated clinically to rule out colonization as they may need proper antifungal treatment. Indiscriminate use of antifungals may lead to the emergence of antifungal drug resistance.

Heterogeneity of Inflammatory Processes and Pathways Driving Chronic Obstructive Pulmonary Disease Pathology

Two symposia occurred during the European Respiratory Society (ERS) Congress 2024, highlighting the heterogeneity in chronic inflammatory pathways that underlie chronic obstructive pulmonary disease (COPD) pathophysiology. In 'A Breath of Fresh Air: A Greater Understanding of COPD With Type 2 Inflammation', Henrik Watz (Chair), German Center for Lung Research, Grosshansdorf, Germany, provided an overview of both the pathophysiology and the burden of disease of COPD. He discussed how exacerbations, which may be increased in those with evidence of Type 2 inflammation, contribute to the cycle of worsening COPD. Mona Bafadhel, King’s College London, UK, provided an examination of the mechanisms and biomarkers of Type 2 inflammation in COPD. Finally, Alberto Papi, University of Ferrara, Italy, summarised the latest research on biological treatments targeting Type 2 inflammation in COPD. The second symposium, 'Targeting interleukin-33 (IL-33) in COPD: Exploring New Frontiers for COPD Management', discussed inflammation in COPD, focusing on the central role of IL-33 as a mediator for both Type 2 and Type 1/Type 3 inflammation. Klaus Rabe (Chair), LungenClinic, Grosshansdorf, Germany, reviewed the structure and function of IL-33 and its initial processes that lead to downstream immune responses. Stephanie Christenson, University of California, San Francisco, USA, explored how genetic and environmental factors contribute to IL-33 activity in COPD pathology. Next, Paola Rogliani, University of Rome ‘Tor Vergata’, Italy, presented an examination of IL-33 inflammatory processes and evidence from COPD animal models illustrating the role of IL-33 in airway inflammation and lung function decline. Klaus Rabe concluded with an examination of IL-33 as a target for new COPD treatment approaches.

Pathomorphological Features of Lung Fibrosis in Individuals Occupationally Exposed to Alpha Radiation

The aim of this study was to search for the specific morphological features of radiation-induced lung fibrosis compared to pulmonary fibrosis of another origin, using biological specimens of lung tissue collected from workers internally exposed to alpha radiation. The morphological features of lung fibrosis were defined using biological specimens of lung tissue that had been collected during autopsy examinations from 56 workers diagnosed with plutonium-induced lung fibrosis during life, from 34 workers with lung fibrosis of another origin (due to chronic inflammatory lung diseases) and from 35 workers without clinical pulmonary pathology (controls). The total lung-absorbed dose of gamma radiation from external exposure did not significantly differ among the studied groups, and the total lung-absorbed dose of alpha radiation from internal exposure was significantly higher in workers with plutonium-induced lung fibrosis. To investigate the extracellular matrix components, mono- and polyclonal labeled antibodies against type I, IV, and V collagens were used. In addition, to evaluate the system of extracellular matrix metabolism regulation, the antibodies against matrix metalloproteinases MMP-2, MMP-9, tissue inhibitors of matrix metalloproteinases TIMP-1 and TIMP-2 were used. The study revealed qualitative and quantitative morphological peculiarities of plutonium-induced lung fibrosis compared to lung fibrosis of another origin. This allows us to conclude that plutonium-induced lung fibrosis is a specific type of lung fibrosis, which is characterized with specific location and architectonics of fibrosis foci within the lung, and with changes in levels of collagen, elastic and reticular fibers in the pulmonary stroma. The analysis demonstrated that hyperproduction of type V collagen plays a key role in the development of plutonium-induced lung fibrosis. In addition, the imbalance between the expression of MMPs and their inhibitors plays an important role in the development of lung fibrosis.

Cold ischemia time alters cell-type specific senescence leading to loss of cellular integrity in mouse lungs

Purpose: Ischemia-reperfusion injury (IRI) is a major challenge in lung transplantation often causing graft dysfunction and chronic airway illnesses in recipients. To prevent potential transplant related complications, strict guidelines were put in place to choose viable donor lungs with minimal risk of IRI. These regulations deem most of the donor organs unfit for transplant which then are donated for research to understand the mechanisms of health and diseases in human. However, resected organs that are being transported undergo cold ischemia that can negatively affect the tissue architecture and other cellular functions under study. Thus, it is important to assess how cold ischemia time (CIT) affects the physiological mechanism. In this respect, we are interested in studying how CIT affects cellular senescence in normal aging and various pulmonary pathologies. We thus hypothesized that prolonged CIT exhibits cell-type specific changes in lung cellular senescence in mice. Methods: Lung lobes from C57BL/6J (n = 5–8) mice were harvested and stored in UW Belzer cold storage solution for 0, 4-, 9-, 12-, 24-, and 48-h CIT. Lung cellular senescence was determined using fluorescence (C12FdG) assay and co-immunolabelling was performed to identify changes in individual cell types. Results: We found a rapid decline in the overall lung cellular senescence after 4-h of CIT in our study. Co-immunolabelling revealed the endothelial cells to be most affected by cold ischemia, demonstrating significant decrease in the endothelial cell senescence immediately after harvest. Annexin V-PI staining further revealed a prominent increase in the number of necrotic cells at 4-h CIT, thus suggesting that most of the cells undergo cell death within a few hours of cold ischemic injury. Conclusions: We thus concluded that CIT significantly lowers the cellular senescence in lung tissues and must be considered as a confounding factor for mechanistic studies in the future.

TRPV4 Mediates Alveolar Epithelial Barrier Integrity and Induces ADAM10-Driven E-Cadherin Shedding.

Transient receptor potential vanilloid 4 (TRPV4) channels have been associated with numerous pulmonary pathologies, including hypertension, asthma, and acute lung injury. However, their role in the alveolar epithelium remains unclear. We performed impedance-based resistance measurements in primary differentiated alveolar epithelial type I (AT1) cells from wild-type (WT) and TRPV4-deficient (TRPV4-/-) C57/BL6J mice to detect changes in AT1 barrier integrity upon TRPV4 activation. Both pharmacological (GSK1016790A) and a low pH-driven activation of TRPV4 were quantified, and the downstream effects on adherens junctions were assessed through the Western blotting of epithelial cadherin (E-cadherin) protein levels. Importantly, a drop in pH caused a rapid decrease in AT1 barrier resistance and increased the formation of a ~35 kDa E-cadherin C-terminal fragment, with both effects significantly reduced in TRPV4-/- AT1 cells. Similarly, the pharmacological activation of TRPV4 in AT1 cells triggered an immediate transient loss of barrier resistance and the formation of the same E-cadherin fragment, which was again diminished by TRPV4 deficiency. Moreover, TRPV4-mediated E-cadherin cleavage was significantly reduced by GI254023X, an antagonist of a disintegrin and metalloprotease 10 (ADAM10). Our results confirm the role of TRPV4 in regulating alveolar epithelial barrier permeability and provide insight into a novel signaling pathway by which TRPV4-induced Ca2+ influx stimulates metalloprotease-driven ectodomain shedding.

Case Report: Aspirated Airway Foreign Body Mimicking Endobronchial Mass: A Diagnostic Challenge

Abstract Introduction/Objective Despite advancements in imaging modalities, identifying retained foreign bodies within the lung remains arduous. Detecting small foreign bodies is crucial as they can serve as a focal point for subsequent infections. Initial assessments may mimic malignancy. Herein, we present a case of a retained foreign body masquerading as an endobronchial mass, accompanied by unilateral pleural effusion and persistent hypoxia. Subsequent bronchoscopy showed a pearly white endobronchial mass partially obstructing the segmental bronchus at the posterior basal segment of the right lower lobe of lung with accompanying right pleural effusion and atelectasis. Methods/Case Report This is a 58-year-old male with history of hypertension, deep vein thrombosis, transient ischemic attack, and a recent motor vehicle accident with blunt chest trauma. He had a thoracic spinal cord transection with grade III blunt thoracic aortic injury, developed anasarca, hypoxia, right pleural fluid requiring multiple thoracentesis, and right sided hemothorax requiring massive transfusion protocol. Subsequent evaluations, including bronchoscopic transbronchial forceps biopsies and bronchial wash and pleural fluid cytologic examinations showed no malignant cells. Repeat bronchoscopy was concerning for enlarging mass and obstruction. Bronchoscopy almost 2 months after MVA revealed an endobronchial foreign body (tooth) lodged in the left lower lobe of lung posterior segment. Results (if a Case Study enter NA) N/A Conclusion While aspiration of foreign bodies into the tracheobronchial tree is not uncommon especially in children, foreign bodies, particularly teeth, are rare in adults. Bronchial foreign body aspiration may occur in trauma, with diagnosis typically relying on history and physical examination. Detection remains challenging despite imaging advancements, with implications including infection nidus formation. In our case, delayed diagnosis highlights the importance of considering unusual etiologies in persistent pulmonary pathology. Retrospective imaging analysis and CT findings suggested a foreign body, emphasizing the utility of imaging in suspected cases. Prompt surgical intervention is crucial to prevent complications such as recurrent infections.

FPR1 signaling aberrantly regulates S100A8/A9 production by CD14+FCN1hi macrophages and aggravates pulmonary pathology in severe COVID-19

Excessive alarmins S100A8/A9 escalate the inflammation and even exacerbate immune-driven thrombosis and multi-organ damage. However, the regulatory mechanisms of S100A8/A9 expression in infectious diseases remain unclear. In this study, high-dimensional transcriptomic data analyses revealed a high proportion of CD14+FCN1hi macrophages within the pulmonary niche post-severe SARS-CoV-2 infection. By constructing the S100-coexpression gene list and supervised module scoring, we found that CD14+FCN1hi macrophages presented the highest scores of alarmin S100, and possibly served as the trigger and amplifier of inflammation in severe COVID-19. These CD14+FCN1hi cells lacked the positive regulatory activity of transcription factor PPARγ, and lost their differentiation ability towards mature macrophages. Ex vivo experiments further validated that the epithelial cells with high ORF-3a expression promoted the expression and secretion of S100A8/A9 through ANXA1/SAA1-FPR1 signaling. S100A8/A9 heterodimers, as well as the co-localization of S100A8/A9 with microtubules, were both diminished by the FPR1 inhibitor. Phospho-kinase protein array indicated that STAT3 promoted transcription, and PLC-γ and ERK1/2 pathways were involved in the hetero-dimerization and unconventional secretion of S100A8/A9. Our study highlights the pivotal role of FPR1 signaling in the excessive production of S100A8/A9 and provides a promising target for the prevention and control of severe COVID-19 and post-acute COVID-19 sequelae.

The Thyroid Hormone Analog GC-1 Mitigates Acute Lung Injury by Inhibiting M1 Macrophage Polarization.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a life-threatening condition with a high mortality rate of ≈40%. Thyroid hormones (THs) play crucial roles in maintaining homeostasis of the cellular microenvironment under stress. The previous studies confirmed that the clinical-stage TH analog GC-1 significantly alleviates pulmonary fibrosis by improving the function of mitochondria in epithelial cells. However, the effects of GC-1 on macrophages in lung injury and the related mechanisms remain unclear. This study evaluated the therapeutic effects of GC-1 in two murine models of lipopolysaccharide (LPS)- or hydrochloric acid (HCl)-induced ALI. Additionally, mouse alveolar macrophages (AMs) and human THP-1-derived macrophages are utilized to investigate the impact of GC-1 on macrophage polarization. GC-1 effectively reduces the inflammatory response and lung injury in ALI mice, as evidenced by neutrophil infiltration, cytokine levels, alveolar fluid clearance, and pulmonary pathology. Notably, GC-1 selectively inhibits M1 macrophage polarization, which may be achieved by impeding NF-κB signaling activation through the DNMT3b-PPARγ-NF-κB pathway in a TH receptor β1 (TRβ1)-dependent manner, consequently suppressing the polarization of macrophages toward the M1 phenotype and overproduction of inflammatory cytokines. Overall, these findings highlight the immunomodulatory property of GC-1 as an anti-inflammatory strategy for ALI/ARDS and inflammation-related diseases.

LungHist700: A dataset of histological images for deep learning in pulmonary pathology

Accurate detection and classification of lung malignancies are crucial for early diagnosis, treatment planning, and patient prognosis. Conventional histopathological analysis is time-consuming, limiting its clinical applicability. To address this, we present a dataset of 691 high-resolution (1200 × 1600 pixels) histopathological lung images, covering adenocarcinomas, squamous cell carcinomas, and normal tissues from 45 patients. These images are subdivided into three differentiation levels for both pathological types: well, moderately, and poorly differentiated, resulting in seven classes for classification. The dataset includes images at 20x and 40x magnification, reflecting real clinical diversity. We evaluated image classification using deep neural network and multiple instance learning approaches. Each method was used to classify images at 20x and 40x magnification into three superclasses. We achieved accuracies between 81% and 92%, depending on the method and resolution, demonstrating the dataset’s utility.

Use of artificial intelligence-powered ECG to differentiate between cardiac and pulmonary pathologies in patients with acute dyspnoea in the emergency department

BackgroundAcute dyspnoea is common in acute care settings. However, identifying the origin of dyspnoea in the emergency department (ED) is often challenging. We aimed to investigate whether our artificial intelligence...

Scutellaria baicalensis ameliorates allergic airway inflammation through agonism and transcriptional regulation of TAS2Rs

Ethnopharmacological relevanceScutellaria baicalensis Georgi (SCB, Huangqin) is a traditional medicinal plant used to treat fever and respiratory diseases. SCB has a good therapeutic effect on asthma and anti-inflammation in traditional clinic use. However, the molecular mechanism and targets of SCB in treating asthma are still unclear. Aim of the studyCombining transcriptomic analysis and in vitro experimental validation, this study aimed to reveal the molecular mechanism and targets of SCB in treating asthma. Materials and methodsThe anti-asthmatic effects of SCB and its active components, scutellarin and oroxylin A, were evaluated in ovalbumin (OVA)-induced rats by analysis of pulmonary function and pathology. The signaling pathways in rat pulmonary tissue were analyzed using transcriptomics and protein interaction network analysis. Calcium mobilization assay and molecular docking were utilized to discover the active compounds from SCB with agonism activity of type 2 taste receptors (TAS2Rs). The anti-asthmatic effect and transcriptional regulation of TAS2Rs regulated by SCB and its active components were analyzed in vitro. ResultsExtracts of SCB (ESB), scutellarin, and oroxylin A ameliorated airway function and inflammation in OVA-induced rats. The anti-asthma mechanism of ESB, scutellarin and oroxylin A was highly related to immune and taste transduction pathways based on transcriptomic analysis, especially the TAS2Rs signaling pathway. ESB was the direct agonist of TAS2R4 and TAS2R14 with EC50 of 209.1 and 217.2 μg/mL based on calcium mobilization assay, respectively. Baicalein was the main active component for TAS2R4 agonism activity, and scutellarin and oroxylin A had weak agonism activity of TAS2R4 and TAS2R14 through calcium mobilization assay and molecular docking. However, scutellarin and oroxylin A significantly upregulated the gene expression of Tas2r108 (the mouse ortholog of the TAS2R4) in lung tissue. ESB, scutellarin, and oroxylin A inhibited LPS-induced lactate dehydrogenase release and gene expression of TNF through transcriptional regulation of TAS2R4 and TAS2R14 on bronchial epithelial cells. ESB and oroxylin A ameliorated IgE-induced β-hexosaminidase release and gene expression of Il4 and Tnf and upregulated gene expression of Tas2r108. ConclusionThese results provided new insight into the anti-asthmatic mechanism of SCB and active components, scutellarin and oroxylin A, through agonism and transcriptional regulation of TAS2Rs to ameliorate allergic airway inflammation.

P1.06C.01 Evaluation of Small Pulmonary Pathology Specimen Management in the Province of Quebec, Canada

P1.06C.01 Evaluation of Small Pulmonary Pathology Specimen Management in the Province of Quebec, Canada