Lung Surface Research Articles

Legionella pneumophila—Klebsiella pneumoniae Pulmonary Coinfection in a COVID-19 Patient: Case Report

Background. Pulmonary superinfections increase the mortality risk among COVID-19 patients, highlighting the need for enhanced understanding to enable early and accurate diagnosis. Methods. We present the case of a patient, a 76-year-old man, hospitalized for a severe form of COVID-19, with a ground-glass pneumonia, involving 40–45% of lung surfaces. Results. In evolution, the clinical condition worsened, presenting leukocytosis with neutrophilia, imaging towards resorption, and computer tomography images showing the appearance of pulmonary condensations in the right lower lobe, the posterior portion of the left lower lobe and pleural collections. Carbapenemase-producing Klebsiella pneumoniae was isolated from the tracheal aspirate, and the real-time polymerase chain reaction test was positive for Klebsiella pneumoniae and Legionella pneumophila. The investigations that were carried out allowed us to establish the coinfections as a probable case of Legionnaire’s disease and a ventilator-associated pneumonia with Klebsiella pneumoniae. Conclusions. The case analysis revealed that rare pneumonias may remain undiagnosed, and coinfections may be conditioned by pathophysiological factors or components of COVID-19 critical form treatment. Enhanced understanding of these aspects in clinical practice may contribute to reducing mortality risk in COVID-19 patients.

Cyproheptadine inhibits in vitro and in vivo lung metastasis and drives metabolic rewiring

BackgroundNon-small cell lung cancer (NSCLC) accounts for 81% of lung cancer cases, among which over 47% presented with distant metastasis at the time of diagnosis. Despite the introduction of targeted therapy and immunotherapy, enhancing the survival rate and overcoming the development of resistance remain a big challenge. Thus, it is crucial to find potential new therapeutics and targets that can mitigate lung metastasis and investigate its effects on biomarkers, such as cellular metabolomics. In the current study, we investigated the role of cyproheptadine (CPH), an FDA-approved anti-histamine drug in lung metastasis in vitro and in vivo.Methods and resultsCPH showed potent cytotoxicity on different lung cancer cell lines in vitro. Moreover, CPH decreased invasion and migration of LLC1 and A549 cells in Matrigel invasion transwell and plate scratch assays. The in vivo LLC1 syngeneic lung cancer model found decreased number of metastatic nodules on the surface of lungs of Setd7 KO mice compared to SETD7 WT. CPH treatment resulted in decreased growth of LLC1 subcutaneous tumors compared to untreated SETD7 WT. Finally, metabolomic study of tumor tissues showed rewiring of metabolomic pathways and downregulation of amino acids, such as arginine, serine, and glycine) in Setd7 KO and WT treated with CPH compared to untreated Setd7 WT mice.ConclusionThese findings identify CPH as a potential therapeutic agent to block metastasis in advanced NSCLC and suggest SETD7 as a potential target for the prevention of lung metastasis.

7076 Inhibiting Oxidosqualene Cyclase, An Enzyme In The Cholesterol Biosynthetic Pathway, Suppresses Lung Metastasis Of Triple-Negative Breast Cancer Cells

Abstract Disclosure: Y. Liang: None. S.M. Hyder: None. Triple-negative breast cancers (TNBC) lack ER, PR and Her2neu proteins that are commonly targeted in breast cancer therapies. As a consequence, women who suffer from TNBC have poor prognosis and limited treatment options, and are usually administered toxic, non-specific chemotherapeutic agents. Drug-resistance almost always occurs, leading to tumor metastasis, the main cause of patient death. New non-toxic therapeutic strategies to control metastasis of TNBC are urgently needed. Cholesterol is an essential structural and functional component of cell membranes that is necessary for the growth of both primary tumors and metastatic colonies that reside in distant organs. Therefore, inhibiting cholesterol production is an attractive therapeutic strategy. Treatment with statins, a class of cholesterol biosynthesis inhibitors that target HMGCoA-reductase, is associated with certain undesirable side effects; consequently, we targeted oxidosqualene cyclase (OSC), an enzyme that occurs downstream of HMGCoA-reductase in the cholesterol biosynthetic pathway, to disrupt tumor metastasis. Potent small molecule inhibitors of OSC have been identified. RO 48-8071 (4′-[6-(allylmethylamino)hexyloxy]-4-bromo-2′-fluorobenzophenone fumarate) (RO), has emerged as a useful chemotherapeutic agent for treating several forms of primary tumors. We developed a mouse model for studying lung metastasis using a MDA-MB-231 variant (LM2) TNBC cell line obtained from Dr. Massagué (Memorial Sloan-Kettering Cancer Center). These are aggressive cells, and injection of only 2 X 105 cells produces detectable lung metastatic colonies in approximately 4-6 weeks. We inoculated female nu/nu mice, 5-6 weeks old, with 2 X 105 MDA-MB-231/LM2 cells in 0.1 ml DMEM/F12 medium without serum via tail vein. Five days after tumor cell inoculation animals received 20 mg/kg (n=6), 40 mg/kg (n=7) RO (ip) or vehicle alone (n=7) every other day for two weeks. Animals were then sacrificed, and both lungs harvested and immediately fixed in Bouin’s fixative. Metastatic colonies on the lung surface were identified and counted under a dissecting microscope. Our study showed that RO effectively reduced lung metastasis without affecting animal weight. Compared with 56 + 7 colonies (Mean ± SEM) in controls given vehicle alone, RO significantly reduced lung metastatic colonies to 28 ± 5 in animals exposed to 20 mg/kg and 6 ± 1 in 40 mg/kg treated animals (p<0.05, ANOVA). Reduction in number of colonies in 40 mg/kg group was also significantly different from colonies counted in 20 mg/kg treated animals. Our study is the first to demonstrate that disruption of cholesterol biosynthesis in a model of human TNBC leads to reduced metastasis in lungs. Further studies will determine mechanisms through which RO suppresses TNBC metastasis to the lungs. Supported by Zalk Missouri Professor Endowment Funds. Presentation: 6/3/2024

7076 Inhibiting Oxidosqualene Cyclase, an Enzyme in the Cholesterol Biosynthetic Pathway, Suppresses Lung Metastasis of Triple-negative Breast Cancer Cells

Abstract Disclosure: Y. Liang: None. S.M. Hyder: None. Triple-negative breast cancers (TNBC) lack ER, PR and Her2neu proteins that are commonly targeted in breast cancer therapies. As a consequence, women who suffer from TNBC have poor prognosis and limited treatment options, and are usually administered toxic, non-specific chemotherapeutic agents. Drug-resistance almost always occurs, leading to tumor metastasis, the main cause of patient death. New non-toxic therapeutic strategies to control metastasis of TNBC are urgently needed. Cholesterol is an essential structural and functional component of cell membranes that is necessary for the growth of both primary tumors and metastatic colonies that reside in distant organs. Therefore, inhibiting cholesterol production is an attractive therapeutic strategy. Treatment with statins, a class of cholesterol biosynthesis inhibitors that target HMGCoA-reductase, is associated with certain undesirable side effects; consequently, we targeted oxidosqualene cyclase (OSC), an enzyme that occurs downstream of HMGCoA-reductase in the cholesterol biosynthetic pathway, to disrupt tumor metastasis. Potent small molecule inhibitors of OSC have been identified. RO 48-8071 (4′-[6-(allylmethylamino)hexyloxy]-4-bromo-2′-fluorobenzophenone fumarate) (RO), has emerged as a useful chemotherapeutic agent for treating several forms of primary tumors. We developed a mouse model for studying lung metastasis using a MDA-MB-231 variant (LM2) TNBC cell line obtained from Dr. Massagué (Memorial Sloan-Kettering Cancer Center). These are aggressive cells, and injection of only 2 X 10[5] cells produces detectable lung metastatic colonies in approximately 4-6 weeks. We inoculated female nu/nu mice, 5-6 weeks old, with 2 X 10[5] MDA-MB-231/LM2 cells in 0.1 ml DMEM/F12 medium without serum via tail vein. Five days after tumor cell inoculation animals received 20 mg/kg (n=6), 40 mg/kg (n=7) RO (ip) or vehicle alone (n=7) every other day for two weeks. Animals were then sacrificed, and both lungs harvested and immediately fixed in Bouin’s fixative. Metastatic colonies on the lung surface were identified and counted under a dissecting microscope. Our study showed that RO effectively reduced lung metastasis without affecting animal weight. Compared with 56 + 7 colonies (Mean ± SEM) in controls given vehicle alone, RO significantly reduced lung metastatic colonies to 28 ± 5 in animals exposed to 20 mg/kg and 6 ± 1 in 40 mg/kg treated animals (p<0.05, ANOVA). Reduction in number of colonies in 40 mg/kg group was also significantly different from colonies counted in 20 mg/kg treated animals. Our study is the first to demonstrate that disruption of cholesterol biosynthesis in a model of human TNBC leads to reduced metastasis in lungs. Further studies will determine mechanisms through which RO suppresses TNBC metastasis to the lungs. Supported by Zalk Missouri Professor Endowment Funds. Presentation: 6/3/2024

Shock wave damage from the ventral side in primary blast injury: An experimental study in pigs

Aim/PurposeThis study aimed to apply a shock wave from the ventral side of a pig and examine its effect to use the results for new body armor production for humans. MethodsSeven male hybrid pigs were used. Each pig was placed under general anesthesia on the experimental table in a blast tube to expose the left lateral position from the front chest area, and shock waves generated by compressed air at 3.0 MPa were applied. We examined changes in vital signs and arterial blood gas in the hyper-acute phase and computed tomography (CT) images, and autopsies were performed for organ damage after 3 h of observation. Pathological examination was performed for lung damage, which is considered a characteristic of shock wave injury. ResultsAll seven pigs survived. Respiratory arrest occurred in two pigs; however, spontaneous breathing resumed promptly afterward. Hypotension occurred at a frequency of 4. No bradycardia or cardiac arrest was observed in any pig. In the arterial blood gas analysis before and immediately after shock wave exposure and 1 hour later, PaO2 decreased immediately but tended to improve thereafter. CT revealed pulmonary contusions and multiple bulla-like lesions on the surface of the lungs. An autopsy showed lung injury in all pigs, particularly in five cases with bulla-like lesions of various sizes on the lung surface across all lobes. Pathological findings showed visceral pleural detachment with elastic fibers from the lung parenchyma, and the cavity lesion on the lung surface comprised bullae. The degree of intra-abdominal hemorrhage varied; however, all but one case showed splenic injury. ConclusionNone of the pigs exposed to shock waves from the ventral side died; however, most showed multiple bullae on the lung surface with lung contusion and splenic injury, which may have been greater than those exposed from the dorsal side. This may be due to the direct impact of the shock wave proceeding from the epigastrium and subcostal region, which are not protected by the skeletal structure of the thorax. These characteristics should be considered when producing new body armor for humans to protect the body from shock waves.

The effect of rewarming ischemia on tissue transcriptome and metabolome signatures: a clinical observational study in lung transplantation

BACKGROUND:In lung transplantation (LuTx), various ischemic phases exist, yet the rewarming ischemia time (RIT) during implantation has often been overlooked. During RIT, lungs are deflated and exposed to the body temperature in the recipient's chest cavity. Our prior clinical findings demonstrated that prolonged RIT increases the risk of primary graft dysfunction. However, the molecular mechanisms of rewarming ischemic injury in this context remain unexplored. We aimed to characterize the rewarming ischemia phase during LuTx by measuring organ temperature and comparing transcriptome and metabolome profiles in tissue obtained at the end versus the start of implantation. METHODSIn a clinical observational study, 34 double-LuTx with ice preservation were analyzed. Lung core and surface temperature (n=65 and 55 lungs) was measured during implantation. Biopsies (n=59 lungs) were wedged from right middle lobe and left lingula at start and end of implantation. Tissue transcriptomic and metabolomic profiling were performed. RESULTSTemperature increased rapidly during implantation, reaching core/surface temperatures of 21.5°C/25.4°C within 30min. Transcriptomics showed increased pro-inflammatory signaling and oxidative stress at the end of implantation. Upregulation of NLRP3 and NFKB1 correlated with RIT. Metabolomics indicated elevated levels of amino acids, hypoxanthine, uric acid, cysteineglutathione disulfide alongside decreased levels of glucose and carnitines. Arginine, tyrosine, and 1-carboxyethylleucine showed correlation with incremental RIT. CONCLUSIONSThe final rewarming ischemia phase in LuTx involves rapid organ rewarming, accompanied by transcriptomic and metabolomic changes indicating pro-inflammatory signaling and disturbed cell metabolism. Limiting implantation time and lung cooling represent potential interventions to alleviate rewarming ischemic injury.

Lung Ultrasound Spectroscopy Applied to the Differential Diagnosis of Pulmonary Diseases: An In Vivo Multicenter Clinical Study.

Lung ultrasound (LUS) is an important imaging modality to assess the state of the lung surface. However, current LUS approaches are based on subjective interpretation of imaging artifacts, which results in poor specificity as quantitative evaluation lacks. The latter could be improved by adopting LUS spectroscopy of vertical artifacts. Indeed, parameterizing these artifacts with native frequency, bandwidth, and total intensity ( [Formula: see text]) already showed potentials in differentiating pulmonary fibrosis (PF). In this study, we acquired radio frequency (RF) data from 114 patients. These data (representing the largest LUS RF dataset worldwide) were acquired by utilizing a multifrequency approach, implemented with an ULtrasound Advanced Open Platform (ULA-OP). Convex (CA631) and linear (LA533) probes (Esaote, Florence, Italy) were utilized to acquire RF data at three (2, 3, and 4 MHz), and four (3, 4, 5, and 6 MHz) imaging frequencies. A multifrequency analysis was conducted on vertical artifacts detected in patients having cardiogenic pulmonary edema (CPE), pneumonia, or PF. These artifacts were characterized by the three abovementioned parameters, and their mean values were used to project each patient into a feature space having up to three dimensions. Binary classifiers were used to evaluate the performance of these three mean features in differentiating patients affected by CPE, pneumonia, and PF. Acquisitions of multifrequency data performed with linear probe lead to accuracies up to 85.43% in the differential diagnosis of these diseases (convex probes' maximum accuracy was 74.51%). Moreover, the results showed high potentials of mean [Formula: see text] (by itself or combined with other features) in improving LUS specificity.

A New Method Proposed for the Estimation of Exposure to Atmospheric Pollution through the Analysis of Black Pigments on the Lung Surface

Megacities can be considered excellent laboratories for studying the effects of the urban environment on human health. Typically, exposure to pollution is estimated according to daily or annual averages of pollutant concentrations, collected at monitoring stations, using satellite data for remote sensing of pollutant levels, considering proximity to major roads, or through personal exposure monitoring with portable sensors. However, these approaches fall short in identifying individual exposure values over a lifetime. It is well established that individuals living in large urban areas inhale atmospheric particles containing carbonaceous components, resulting in the deposition of black pigments in lung tissue, known as black carbon or anthracosis. This study aims to detail the procedures for assessing the deposition of such pigments, which serve as an estimate of an individual’s exposure to atmospheric pollution particles. Data collection involves administering detailed questionnaires and capturing lung images in the autopsy room. The analysis is based on macroscopic quantification of black pigments, supplemented by an evaluation of personal habits and the clinical histories of the individuals. This method of estimating lifetime exposure to inhaled particles provides a valuable tool for understanding the correlation between urban living and its potential health effects.

Low-Volume Ex Situ Lung Perfusion System for Single Lung Application in a Small Animal Model Enables Optimal Compliance With "Reduction" in 3R Principles of Animal Research.

Ex situ lung perfusion (ESLP) is used for organ reconditioning, repair, and re-evaluation prior to transplantation. Since valid preclinical animal models are required for translationally relevant studies, we developed a 17mL low-volume ESLP for double- and single-lung application that enables cost-effective optimal compliance "reduction" of the 3R principles of animal research. In single-lung mode, ten Fischer344 and Lewis rat lungs were subjected to ESLP and static cold storage using STEEN or PerfadexPlus. Key perfusion parameters, thermal lung imaging, blood gas analysis (BGA), colloid oncotic pressure (COP), lung weight gain, histological work-up, and cytokine analysis were performed. Significant differences between perfusion solutions but not between the rat strains were detected. Most relevant perfusion parameters confirmed valid ESLP with homogeneous lung perfusion, evidenced by uniform lung surface temperature. BGA showed temperature-dependent metabolic activities with differences depending on perfusion solution composition. COP is not decisive for pulmonary oedema and associated weight gain, but possibly rather observed chemokine profile and dextran sensitivity of rats. Histological examination confirmed intact lung architecture without infarcts or hemorrhages due to optimal organ procurement and single-lung application protocol using our in-house-designed ESLP system.

Ginsenoside Rb prevents the metastasis of hepatocarcinoma by blocking the platelet-tumor cell interaction.

The interaction between platelets and tumor cells is a crucial step in the progression of tumor metastasis. Blocking platelet-tumor cell interaction is a potential target against metastasis. Ginsenoside Rb (G-Rb) exhibits potential anti-tumor pharmacological properties and may offer a therapeutic option for cancer. This study aimed to investigate anti-metastatic effects of G-Rb through regulating the crosstalk of platelets with tumor cells. In order to explore anti-metastatic effects of G-Rb in vitro, HepG2 cell and platelets were co-cultured to mimic the interaction of platelets with tumor cells. Wound healing and Transwell assays were used to assess the effect of G-Rb on cell migration and invasion. The expression of epithelial-mesenchymal transition (EMT)-related markers was determined by RT-qPCR and western blot assays. The aggregation and activation of platelets were detected by flow cytometry. Moreover, a lung metastasis model of mice was established to evaluate inhibitory effects of G-Rb in vivo. Metastatic nodules on the lung surface were counted and sections of lung tissues were stained by H&E. G-Rb effectively suppressed tumor metastasis in the co-culture of platelets with HepG2 cell. First, G-Rb treatment significantly inhibited the migration and invasion of HepG2 cells induced by platelets. Second, the expressions of EMT-related markers, including N-cadherin, Snail, and MMP9, were decreased by the treatment of G-Rb in the presence of platelets. Meanwhile, G-Rb also suppressed platelet hyperactivity by regulating the adhesion to tumor cells, activation, TCIPA, and TGF-β1 secretion of platelets in vitro. In addition, the results of in vivo experiments proved G-Rb administration not only significantly decreased lung metastasis but also attenuated platelets aberrant aggregation and activation in vivo. Our findings showed that G-Rb inhibited tumor metastasis and platelet activation through mediating platelet-tumor cell interaction, indicating the potential values of G-Rb in tumor metastasis therapy.

Endobronchial Closure for Peripheral Pulmonary Air Leakage

Introduction: A minimally invasive alternative to surgery for treating pneumothorax has been developed, aiming to reduce risks while maintaining efficacy. This study conducted basic experiments using ex vivo and in vivo pig lung employing a super-thin catheter for treatment. This new device injects fibrin glue directly into the responsible lesion to close the air leak, which has two features: thin design and double-lumen. Methods: The experimental setup involved utilizing trachea and both lung specimens from pigs under positive pressure ventilation. To simulate pneumothorax, artificial fistulas were created on the lung surfaces. The super-thin catheter, guided through a bronchoscope near the fistula, was used to embolize the peripheral bronchus by injecting a fibrin preparation. Then, an air leak test was conducted afterward to assess the efficacy of the treatment. Additionally, a similar pneumothorax model was induced in alive pig under general anesthesia to evaluate its curability. Results: In the extracted pig lungs, embolization was performed in 21 cases, resulting in the cessation of air leaks in 19 cases, corresponding to a 90.5% cure rate. Notably, no major adverse events occurred with the treatment devices. Similarly, in living pigs, pneumothorax was successfully treated, with no recurrence observed up to the seventh postoperative day. Conclusion: The novel treatment device utilizing a super-thin catheter offers a minimally invasive and highly curative option for pneumothorax. These promising results suggest the potential for further development and human clinical trials, which could revolutionize the treatment of pneumothorax, reducing risks and improving outcomes.

Biomechanical Properties and Cellular Responses in Pulmonary Fibrosis.

Pulmonary fibrosis is a fatal lung disease affecting approximately 5 million people worldwide, with a 5-year survival rate of less than 50%. Currently, the only available treatments are palliative care and lung transplantation, as there is no curative drug for this condition. The disease involves the excessive synthesis of the extracellular matrix (ECM) due to alveolar epithelial cell damage, leading to scarring and stiffening of the lung tissue and ultimately causing respiratory failure. Although multiple factors contribute to the disease, the exact causes remain unclear. The mechanical properties of lung tissue, including elasticity, viscoelasticity, and surface tension, are not only affected by fibrosis but also contribute to its progression. This paper reviews the alteration in these mechanical properties as pulmonary fibrosis progresses and how cells in the lung, including alveolar epithelial cells, fibroblasts, and macrophages, respond to these changes, contributing to disease exacerbation. Furthermore, it highlights the importance of developing advanced in vitro models, based on hydrogels and 3D bioprinting, which can accurately replicate the mechanical and structural properties of fibrotic lungs and are conducive to studying the effects of mechanical stimuli on cellular responses. This review aims to summarize the current understanding of the interaction between the progression of pulmonary fibrosis and the alterations in mechanical properties, which could aid in the development of novel therapeutic strategies for the disease.

Significance of transthoracic ultra-sonography in early detection of patients with interstitial lung diseases in Aswan University Hospital

BackgroundRecently, the diagnosis and follow-up of numerous pulmonary diseases such as pneumothorax, pneumonia, and pleural effusion were easily by use of conventional ultrasound, and the maximum usefulness of transthoracic ultrasonography (TUS) in pulmonary diseases especially diffuse parenchymal lung disease has not been detected yet. This study was conducted to determine the value of transthoracic ultrasonography in patients with interstitial lung disease (ILD). Moreover, the viable correlations of the ultrasound findings with the functional and radiological findings of ILDs had been assessed.ResultsTUS diagnosis was positive in 73 cases, there was a substantial variation between the two groups classified according to ultrasonographic diagnosis regarding age and smoking history (p = 0.003 and 0.013 respectively). All the patients with usual interstitial pneumonia (n = 42) and Indeterminate UIP (n = 49) had positive ultra-sonographic findings [p = 0.041 and 0.001 accordingly]. Regarding pulmonary function tests, there was a considerable variance between both groups regarding FVC, PEF, FEF25-75, FEV1/VC (p = 0.037, 0.029, 0.015, and 0.000 accordingly). The most positive US diagnosis areas were upper lateral, lateral basal, and interscapular areas. There was a weak negative correlation between TUS diagnosis and FVC [r = − 0.25, p = 0.026].ConclusionWe concluded the great significant value of TUS in the diagnosis and follow-up of patients with interstitial lung diseases. It had an extremely thoughtful role in the diagnosis of ILD by detection of multiple B-lines distribution emerging from pleura and extending in the entire lung surface. The use of TUS in early detection and follow-up of ILDs reduced the cost.

A Cohort Study of Serum 25-Hydroxyvitamin D Levels and Lung Disease in Preterm Infants

Objectives: To analyze the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and lung diseases (wet lung, RDS, BPD, pneumothorax) in preterm infants. Methods: Preterm infants (corrected gestational age <37 weeks) hospitalized in the neonatology department of Yan'an University Hospital from January 2023 to December 2023 were selected as the study subjects, and their clinical data and 25-hydroxyvitamin D [25(OH)D] levels in the first 24 h of life were collected (by the random number table method to avoid selection bias) in a retrospective cohort study with the basis of the Serum 25(OH)D level was used to categorize preterm infants into high vitamin D and low vitamin D groups, and to compare the incidence of lung diseases in preterm infants in the 2 groups. Results: A total of 414 preterm infants were selected, and 237 preterm infants were finally included for analysis. The mean serum 25(OH)D level in preterm infants within 24 hours of birth was 16.97 ng/mL. 140 cases in the low-vitamin D group had a serum 25(OH)D level of (11.88± 2.74) ng/mL. 97 cases in the high-vitamin D group had a serum 25(OH)D level of (24.31± 7.52) ng/mL; the rate of births in the fall in the low-vitamin D group was was significantly higher than that of the high-vitamin D group (P<0.05), the utilization rate of lung surface active substance was higher than that of the high-vitamin D group (P<0.05), and the incidence of RDS and BPD was significantly higher than that of the high-vitamin D group (P<0.05). Univariate logistic regression analysis suggested that season of birth, serum 25(OH)D level, 5 min Apgar score and prenatal hormone use were associated with pulmonary complications in preterm infants (P<0.05). Multifactorial logistic regression analysis showed that higher serum 25(OH)D levels reduced the risk of pulmonary complications in preterm infants, which was statistically significant (B=-0.056, RR= 0.946, 95% CI: 0.910-0.984, P=0.006); higher 5-min Apgar scores had a lower incidence of pulmonary complications in preterm infants, which was statistical significance (B=-0.722, RR= 0.486, 95% CI: 0.281~0.840, P=0.010); prenatal use of hormones will reduce the risk of pulmonary complications in preterm infants (B=-0.763, RR= 0.466, 95% CI: 0.261~0.833, P=0.010). Conclusion: Low vitamin D levels at birth in preterm infants may increase the incidence of RDS and BPD.

Ultrasound description of the coelomic cavity of the axolotl (Ambystoma mexicanum) in a clinically healthy population: a pilot study

Axolotls (Ambystoma mexicanum) are extensively studied for their relevance in human medical research. Despite being critically endangered in the wild, they have gained popularity as household pets. Although they have been kept in captivity for over a century, detailed descriptions of their coelomic organ anatomy remain limited. Also, this species exhibits significant variations compared to other amphibians. Ultrasound is a non-invasive and painless medical imaging technique, ideally suited for investigating internal organs or structures. This study focused on describing the ultrasound appearance of the axolotl coelomic cavity. It details the identification, localization and parenchymal description of major organs in 28 neotenic axolotls using ultrasound frequencies ranging from 7 to 15 MHz. The accuracy of the results was validated by comparing ultrasound findings with necropsy results from one male and one female axolotl. The heart, lung surface, liver and reproductive tracts were visualized. Measurements, along with confidence intervals, were calculated for the spleen, kidneys, testicles, gastric wall, gallbladder, and pylorus. Occasional detection of hyperechoic millimetric particles in the gallbladder or ascites was noted. However, visualization of the pancreas and bladder was not possible. This research outcomes involve the development of a comprehensive atlas comprising images obtained throughout the study. Additionally, the experiment established a reproducible and readily accessible protocol for conducting anatomy-morphological assessments in axolotl medicine. This protocol stands as a crucial preliminary stage before advancing to lesion identification.

Thorium Alters Lung Surfactant Protein Expression in Alveolar Epithelial Cells: In Vitro and In Vivo Investigation.

Thorium-232 (Th), the most abundant naturally occurring nuclear fuel, has been identified as a sustainable source of energy. In view of its large-scale utilization and human evidence of lung disorders and carcinogenicity, it is imperative to understand the effect of Th exposure on lung cells. The present study investigated the effect of Th-dioxide (1-100 μg/mL, 24-48 h) on expression of surfactant proteins (SPs) (SP-A, SP-B, SP-C, and SP-D, which are essential to maintain lung's surface tension and host-defense) in human lung cells (WI26 and A549), representative of alveolar cell type-I and type-II, respectively. Results demonstrated the inhibitory effect of Th on transcriptional expression of SP-A, SP-B, and SP-C. However, Th promoted the mRNA expression of SP-D in A549 and reduced its expression in WI26. To a significant extent, the effect of Th on SPs was found to be in accordance with their protein levels. Moreover, Th exposure altered the extracellular release of SP-D/A from A549, which remained unaltered in WI26. Our results suggested the differential role of oxidative stress and ATM and HSP90 signaling in Th-induced alterations of SPs. These effects of Th were found to be consistent in lung tissues of mice exposed to Th aerosols, suggesting a potential role of SPs in Th-associated lung disorders.

A mouse model of wildfire smoke-induced health effects: sex differences in acute and sustained effects of inhalation exposures

Due to climate change, wildfires have increased in intensity and duration. While wildfires threaten lives directly, the smoke has more far-reaching adverse health impacts. During an extreme 2017 wildfire event, residents of Seeley Lake, Montana were exposed to unusually high levels of wood smoke (WS) causing sustained effects on lung function (decreased FEV1/FVC). Objective: The present study utilized an animal model of WS exposure to research cellular and molecular mechanisms of the resulting health effects. Methods: Mice were exposed to inhaled WS utilizing locally harvested wood to recapitulate community exposures. WS was generated at a rate resulting in a 5 mg/m3 PM2.5 exposure for five days. Results: This exposure resulted in a similar 0.28 mg/m2 particle deposition (lung surface area) in mice that was calculated for human exposure. As with the community observations, there was a significant effect on lung function, increased resistance, and decreased compliance, that was more pronounced in males at an extended (2 months) timepoint and males were more affected than females: ex vivo assays illustrated changes to alveolar macrophage functions (increased TNFα secretion and decreased efferocytosis). Female mice had significantly elevated IL-33 levels in lungs, however, pretreatment of male mice with IL-33 resulted in an abrogation of the observed WS effects, suggesting a dose-dependent role of IL-33. Additionally, there were greater immunotoxic effects in male mice. Discussion: These findings replicated the outcomes in humans and suggest that IL-33 is involved in a mechanism of the adverse effects of WS exposures that inform on potential sex differences.

Dual-color FISH analyses of xenogeneic human fibroblast sheets transplanted to repair lung pleural defects in an immunocompromised rat model

BackgroundPulmonary air leaks (PALs) due to visceral pleura injury during surgery is frequently observed after pulmonary resections and the complication is difficult to avoid in thoracic surgery. The development of postoperative PALs is the most common cause of prolonged hospitalization. Previously, we reported that PALs sealants using autologous dermal fibroblast sheets (DFSs) harvested from temperature-responsive culture dishes successfully closed intraoperative PALs during lung resection.ObjectiveIn this study, we investigated the fate of human DFSs xenogenetically transplanted onto lung surfaces to seal PALs of immunocompromised rat. Dual-color FISH analyses of human fibroblast was employed to detect transplantation human cells on the lung surface.ResultsOne month after transplantation, FISH analyses revealed that transplanted human fibroblasts still composed a sheet-structure, and histology also showed that beneath the sheet’s angiogenesis migrating into the sheets was observed from the recipient tissues. FISH analyses revealed that even at 3 months after transplantation, the transplanted human fibroblasts still remained in the sheet. Dual-color FISH analyses of the transplanted human fibroblasts were sparsely present as a result of the cells reaching the end of their lifespan, the cells producing extracellular matrix, and remained inside the cell sheet and did not invade the lungs of the host.ConclusionsDFS-transplanted human fibroblasts showed that they are retained within cell sheets and do not invade the lungs of the host.

BipoJet Scissors as an Alternative to Laser in Lung Wedge Resection.

An important goal in every lung resection is airtight closure of the resected lung surface. This can be achieved with several techniques, including clamp resection, stapler, laser, and various high-frequency methods.By quantitatively measuring the air fistulaacross the resection surface of porcine lungs, two resection techniques were compared in our study: BipoJet dissecting scissors (Aesculap, Inc., Tuttlingen,Germany) and laser (Ceralas HPD®, Biolitec Inc., Jena, Germany). Following a stencil, wedge resections were performed in porcine lungs using water-irrigated bipolar scissors and laser (1350nm, 40watts, non-contact mode). The volumeof the air fistula was then measured. The irrigation technique involved the attachment of an irrigation channel to a pair of standard surgical scissors. Asodium chloride (NaCl) solution was fed at a defined flow rate, along the blades of the scissors onto the parenchyma. This technique was used on a total of 10 specimens each. Somewhat better pneumostasis was achieved with laser resection, though the difference was small and not statistically significant. The flow rate was 124mL/min/cm² after laser resection and 145 mL/min/cm² after using the BipoJet scissors. The difference was not statistically significant.Water irrigation during resection with the BipoJet scissors prevents the temperature in the tissue from exceeding 100°Cthus avoiding tissue carbonization. These scissors offer the following advantages: ease of use, no need to change instruments, no need for staff training, no protective measures, all-in-one incision/coagulation/dissection, low cost, and a clear surgical field due to the irrigation effect. Resection of lung parenchyma, e.g., during resection of metastases, is easier with BipoJet scissors and comparable to laser resection. This was established both experimentally and by resecting lung metastases.

The people behind the papers - Yongjun Yin and David Ornitz.

During alveologenesis, multiple mesenchymal cell types play crucial roles in maximising the lung surface area. In their study, David Ornitz and colleagues define the repertoire of lung fibroblasts, with a particular focus on alveolar myofibroblasts. To know more about their work, we spoke to the first author, Yongjun Yin, and the corresponding author, David Ornitz, Alumni Endowed Professor at the Department of Developmental Biology, Washington University School of Medicine, St. Louis.