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Background: The first 24 h of infection represent a critical time window in interactions between pathogens and host tissue. However, it is not possible to study such early events in human lung during natural infection due to lack of clinical access to tissue this early in infection. We, therefore, applied RNA sequencing to ex vivo cultured human lung tissue explants (HLTE) from patients with emphysema to study global changes in small noncoding RNA, mRNA, and long noncoding RNA (lncRNA, lincRNA) populations during the first 24 h of infection with influenza A virus (IAV), Mycobacterium bovis Bacille Calmette-Guerin (BCG), and Pseudomonas aeruginosa. Results: Pseudomonas aeruginosa caused the strongest expression changes and was the only pathogen that notably affected expression of microRNA and PIWI-associated RNA. The major classes of long RNAs (> 100 nt) were represented similarly among the RNAs that were differentially expressed upon infection with the three pathogens (mRNA 77–82%; lncRNA 15–17%; pseudogenes 4–5%), but lnc-DDX60-1, RP11-202G18.1, and lnc-THOC3-2 were part of an RNA signature (additionally containing SNX10 and SLC8A1) specifically associated with IAV infection. IAV infection induced brisk interferon responses, CCL8 being the most strongly upregulated mRNA. Single-cell RNA sequencing identified airway epithelial cells and macrophages as the predominant IAV host cells, but inflammatory responses were also detected in cell types expressing few or no IAV transcripts. Combined analysis of bulk and single-cell RNAseq data identified a set of 6 mRNAs (IFI6, IFI44L, IRF7, ISG15, MX1, MX2) as the core transcriptomic response to IAV infection. The two bacterial pathogens induced qualitatively very similar changes in mRNA expression and predicted signaling pathways, but the magnitude of change was greater in P. aeruginosa infection. Upregulation of GJB2, VNN1, DUSP4, SerpinB7, and IL10, and downregulation of PKMYT1, S100A4, GGTA1P, and SLC22A31 were most strongly associated with bacterial infection. Conclusions: Human lung tissue mounted substantially different transcriptomic responses to infection by IAV than by BCG and P. aeruginosa, whereas responses to these two divergent bacterial pathogens were surprisingly similar. This HLTE model should prove useful for RNA-directed pathogenesis research and tissue biomarker discovery during the early phase of infections, both at the tissue and single-cell level. [ABSTRACT FROM AUTHOR]

Collagen is crucial for tissue structure, functional maintenance, and cellular processes such as proliferation and differentiation. However, the specific changes in collagen expression and its associated genes in the lung tissues of yaks at high altitudes and their relationship with environmental adaptation remain poorly understood. Studying differences in the content of collagen fibers and gene expression between yaks at high (4,500 m) and low (2,600 m) altitudes, as well as between cattle at low altitudes (2,600 m). Using Masson staining, we found that the collagen fiber content in the lung tissues of yaks at low altitude was significantly higher compared to yaks at high altitude and cattle at the same altitude (P < 0.05). It was revealed through transcriptomic analyses that genes differentially expressed between high and low altitude yaks, as well as between low altitude yaks and cattle, were notably enriched in pathways related to cell adhesion, collagen synthesis, focal adhesion, and ECM-receptor interactions. Specifically, genes involved in mesenchymal collagen synthesis (e.g., COL1A1, COL1A2, COL3A1), basement membrane collagen synthesis (e.g., COL4A1, COL4A2, COL4A4, COL4A6), and peripheral collagen synthesis (e.g., COL5A1, COL6A1, COL6A2, COL6A3) were significantly upregulated in the lung tissues of yaks at low altitude compared to their high altitude counterparts and cattle (P < 0.05). In conclusion, yaks at lower altitudes exhibit increased collagen synthesis by upregulating collagen gene expression, which contributes to maintaining alveolar stability and septal flexibility. Conversely, the expression of collagen genes in yak lung tissues was down-regulated with the increase in altitude, and it was speculated that the decrease in collagen may be used to constrain the function of elastic fibers that are more abundant at high altitude, so as to enable them to adapt to the harsh environment with hypoxia and high altitude. This adaptation mechanism highlights the role of collagen in environmental acclimatization and contributes to our understanding of how altitude and species influence collagen-related physiological processes in yaks. [ABSTRACT FROM AUTHOR]

Abstract Background The first 24 h of infection represent a critical time window in interactions between pathogens and host tissue. However, it is not possible to study such early events in human lung during natural infection due to lack of clinical access to tissue this early in infection. We, therefore, applied RNA sequencing to ex vivo cultured human lung tissue explants (HLTE) from patients with emphysema to study global changes in small noncoding RNA, mRNA, and long noncoding RNA (lncRNA, lincRNA) populations during the first 24 h of infection with influenza A virus (IAV), Mycobacterium bovis Bacille Calmette-Guerin (BCG), and Pseudomonas aeruginosa. Results Pseudomonas aeruginosa caused the strongest expression changes and was the only pathogen that notably affected expression of microRNA and PIWI-associated RNA. The major classes of long RNAs (> 100 nt) were represented similarly among the RNAs that were differentially expressed upon infection with the three pathogens (mRNA 77–82%; lncRNA 15–17%; pseudogenes 4–5%), but lnc-DDX60-1, RP11-202G18.1, and lnc-THOC3-2 were part of an RNA signature (additionally containing SNX10 and SLC8A1) specifically associated with IAV infection. IAV infection induced brisk interferon responses, CCL8 being the most strongly upregulated mRNA. Single-cell RNA sequencing identified airway epithelial cells and macrophages as the predominant IAV host cells, but inflammatory responses were also detected in cell types expressing few or no IAV transcripts. Combined analysis of bulk and single-cell RNAseq data identified a set of 6 mRNAs (IFI6, IFI44L, IRF7, ISG15, MX1, MX2) as the core transcriptomic response to IAV infection. The two bacterial pathogens induced qualitatively very similar changes in mRNA expression and predicted signaling pathways, but the magnitude of change was greater in P. aeruginosa infection. Upregulation of GJB2, VNN1, DUSP4, SerpinB7, and IL10, and downregulation of PKMYT1, S100A4, GGTA1P, and SLC22A31 were most strongly associated with bacterial infection. Conclusions Human lung tissue mounted substantially different transcriptomic responses to infection by IAV than by BCG and P. aeruginosa, whereas responses to these two divergent bacterial pathogens were surprisingly similar. This HLTE model should prove useful for RNA-directed pathogenesis research and tissue biomarker discovery during the early phase of infections, both at the tissue and single-cell level.

The aim of this study was to investigate changes in the ultrastructure of lung tissue during the chronic course of pneumonia and the development of respiratory failure against this background. Materials and methods. Research was conducted on 16 male Wistar rats weighing 250-270 g, in which experimental pneumonia (EP) was attributed to aspiration and/or partial post-traumatic pneumonia. The 1st group of rats consisted of control animals (n=6), the 2nd group consisted of experimental animals with experimental pneumonia on the 4-5th day of the development of the disease (n=5), and the 3rd group consisted of experimental animals 6 weeks after EP modeling (n=5). The breathing and gas exchange patterns were recorded using an original automated device consisting of a mass spectrometer MH6202 (Ukraine) and a pneumotachograph with a breathing sensor MPX5050 (Freescale, Netherlands). Structural features of the lungs during pneumonia were studied using electron microscopy. In addition, studies of the ultrastructure of lung tissue were conducted in 2 groups of people: patients with chronic pneumonia and respiratory failure, operated on for medical reasons (n=5) (duration of pneumonia – 6 to 8 weeks) and deceased with a diagnosis of restrictive respiratory failure (n=6) (duration of pneumonia – from 1 to 1.5 years). Results. It has been shown that in experimental pneumonia, there are significant changes in the ultrastructure of lung tissue, resulting in damage to the air–blood barrier, the surfactant system, and the mitochondrial apparatus. Similar changes were observed in patients diagnosed with pneumonia. In both cases, respiratory failure developed against the background of interstitial and/or intra-alveolar pulmonary edema. Conclusions. The chronicity of this process is accompanied by the formation of pneumosclerosis of various degrees of severity with the preservation of changes in breathing patterns, gas exchange, and metabolic processes in lung tissue and pulmonary edema.

Background and Objectives: In this study, we aimed to investigate the effects of bosentan, an endothelin receptor antagonist, on endothelin-1 (ET-1), hypoxia-inducible factor-1 (HIF-1), nuclear factor-kappa B (NF-κB), and tumor necrosis factor (TNF)-α as inflammation markers, pro-oxidant antioxidant balance (PAB), and total antioxidant capacity (TAC) levels as oxidative stress parameters in lung tissues of rats in an experimental model of pulmonary contusion (PC) induced by blunt thoracic trauma. Materials and Methods: Thirty-seven male Sprague-Dawley rats were divided into five groups. C: The control group (n = 6) consisted of unprocessed and untreated rats. PC3 (n = 8) underwent 3 days of PC. PC-B3 (n = 8) received 100 mg/kg bosentan and was given orally once a day for 3 days. The PC7 group (n = 7) underwent 7 days of PC, and PC-B7 (n = 8) received 100 mg/kg bosentan and was given orally once a day for 7 days. Results: ET-1, NF-κB, TNF-α, HIF-1α, and PAB levels were higher, while TAC activity was lower in all groups compared with the control (p < 0.05). There was no significant difference in ET-1 and TNF-α levels between the PC-B3 and PC-B7 groups and the control group (p < 0.05), while NF-κB, HIF-1α, and PAB levels were still higher in both the PC-B3 and PC-B7 groups than in the control group. Bosentan decreased ET-1, NF-κB, TNF-α, HIF-1α, and PAB and increased TAC levels in comparison to the nontreated groups (p < 0.05). Conclusions: Bosentan decreased the severity of oxidative stress in the lungs and reduced the inflammatory reaction in rats with PC induced by blunt thoracic trauma. This suggests that bosentan may have protective effects on lung injury mechanisms by reducing hypoxia, inflammation, and oxidative stress. If supported by similar studies, bosentan can be used in both pulmonary and emergency clinics to reduce ischemic complications, inflammation, and oxidative stress in some diseases that may be accompanied by ischemia. [ABSTRACT FROM AUTHOR]

The widely used Vawter-Fung (VF) lung tissue constitutive model, originally developed to model respiration, was assessed for applicability to impact human body models (HBMs). A review of the mechanical properties of lung tissue demonstrated existing parameter sets for the VF model encompassed a wide range of stiffness relative to experimental data. Consistent experimental datasets of lung tissue for uniaxial and biaxial tension were identified, and new parameters were fit to the VF model. A thoracic pendulum impact using a contemporary HBM was used to assess existing literature parameter sets, and the new parameters. The VF model parameters presented in this study produced uniaxial and biaxial tension response with improved hyperelastic response compared to experimental data and previously reported parameters. The VF surface tension component did not contribute substantially to the lung response in impact. The proposed VF model parameters were numerically stable for impact simulations and use in HBMs. [ABSTRACT FROM AUTHOR]

Collagen is crucial for tissue structure, functional maintenance, and cellular processes such as proliferation and differentiation. However, the specific changes in collagen expression and its associated genes in the lung tissues of yaks at high altitudes and their relationship with environmental adaptation remain poorly understood. Studying differences in the content of collagen fibers and gene expression between yaks at high (4,500 m) and low (2,600 m) altitudes, as well as between cattle at low altitudes (2,600 m). Using Masson staining, we found that the collagen fiber content in the lung tissues of yaks at low altitude was significantly higher compared to yaks at high altitude and cattle at the same altitude (P < 0.05). It was revealed through transcriptomic analyses that genes differentially expressed between high and low altitude yaks, as well as between low altitude yaks and cattle, were notably enriched in pathways related to cell adhesion, collagen synthesis, focal adhesion, and ECM-receptor interactions. Specifically, genes involved in mesenchymal collagen synthesis (e.g., COL1A1, COL1A2, COL3A1), basement membrane collagen synthesis (e.g., COL4A1, COL4A2, COL4A4, COL4A6), and peripheral collagen synthesis (e.g., COL5A1, COL6A1, COL6A2, COL6A3) were significantly upregulated in the lung tissues of yaks at low altitude compared to their high altitude counterparts and cattle (P < 0.05). In conclusion, yaks at lower altitudes exhibit increased collagen synthesis by upregulating collagen gene expression, which contributes to maintaining alveolar stability and septal flexibility. Conversely, the expression of collagen genes in yak lung tissues was down-regulated with the increase in altitude, and it was speculated that the decrease in collagen may be used to constrain the function of elastic fibers that are more abundant at high altitude, so as to enable them to adapt to the harsh environment with hypoxia and high altitude. This adaptation mechanism highlights the role of collagen in environmental acclimatization and contributes to our understanding of how altitude and species influence collagen-related physiological processes in yaks.

The threat of the spread of small ruminant plague to livestock in a number of countries makes the study of the mechanisms of development and prevention of this disease a priority area of research. Therefore, the purpose of the study was to investigate the changes in the blood system and organs of the immune system in small ruminant plague, which led to the development of immunodeficiency in the body of infected animals. Haematological and histological methods were used in the study. As a result of the work carried out, a decrease in the total number of leukocytes in the peripheral blood from 12.4 to 7.3×109/l was detected in 3 sheep that died from small ruminant plague. There was also a shift in the normal ratio of granulocytes to agranulocytes from 1:1 to 2.5:1 towards granulocytes, which was provoked by a sharp decrease in the number of lymphocytes from 49% to 25% in the leukocyte blood count. Such changes in the blood system were provoked by significant degenerative changes in the lymphoid tissue of immunocompetent organs – lymph nodes and spleen. Histological examination of the parenchyma of the above organs revealed atrophy of T- and B-dependent zones and apoptosis of lymphocytes. Taken together, these signs – haematological and histological – allow for the conclusion that both the humoral and cellular immune response systems in the body are reduced. In the affected areas of the lungs, an inflammatory reaction is observed with active migration of neutrophils and macrophages to the inflammation zone. But the active multiplication of the virus in the lung cells indicates a lack of immunity. Thus, the study revealed the mechanisms of the development of humoral and cellular immunodeficiency in small ruminant plague (SRP), which would allow developing more effective methods of combating this disease

AbstractThis study aimed to investigate the effects of combined exposure to noise (85 dB(A)) and inhaled Toluene (300 ± 10 ppm) on rat lung health. It also aimed to assess the potential therapeutic effects of Olea europaea L. leaves extract (OLE) (40 mg/kg/day) using biochemical, histopathological, and immunohistochemical (IHC) analyses, as well as determination of pro-inflammatory cytokines (TNF-α and IL-1β), and in silico Docking studies. The experiment involved forty-two male Wistar rats divided into seven groups, each exposed to a 6-week/6-hour/day regimen of noise and Toluene. The groups included a control group, rats co-exposed to noise and Toluene, and rats co-exposed to noise and Toluene treated with OLE for different durations. The results indicated that noise and Toluene exposure led to structural damage in lung tissue, oxidative harm, and increased levels of pro-inflammatory cytokines (TNF-α and IL-1β). However, the administration of OLE extract demonstrated positive effects in mitigating these adverse outcomes. OLE treatment reduced lipid peroxidation and enhanced the activities of catalase and superoxide dismutase, indicating its anti-oxidant properties. Furthermore, OLE significantly decreased the levels of pro-inflammatory cytokines compared to the groups exposed to noise and Toluene without OLE treatment. Moreover, the in silico investigation substantiated a robust affinity between COX-2 and OLE components, affirming the anti-inflammatory activity. Overall, our findings suggest that OLE possesses anti-inflammatory and anti-oxidative properties that mitigate the adverse effects of concurrent exposure to noise and Toluene. [ABSTRACT FROM AUTHOR]

The microscopic observation of lung tissue is challenging due to its fragile nature. Xylene and isopropanol are common tissue-clearing reagents used before paraffin embedding, yet no studies have compared these two reagents in lung tissue processing. Due to the well-known health risks xylene could introduce to operators, as well as its environmental hazards, it has long been desired that a less harmful alternative to xylene with the same staining effects be introduced. Thus, we systematically assessed the efficacy of isopropanol as a substitution for xylene. Lung tissue obtained from diseased donors and explanted lungs from recipients were processed simultaneously using either xylene or isopropanol prior to paraffin embedding. Scoring of the overall staining quality after H&E staining, along with the ease of sectioning, was compared systematically. Fluorescent staining was performed to explore alveolar morphology and the overall lectin fluorescence signal between groups. To understand differences in antibody staining, the signal-to-noise ratio (SNR) of smooth muscle actin (SMA) and elastin was examined. No difference was observed with regard to ease of sectioning, staining quality, alveolar circularity, alveolar wall thickness or the SNR between slides processed with xylene or isopropanol. This study demonstrated comparable outcomes of isopropanol and xylene in lung tissue processing, suggesting isopropanol as a more favorable, operator- and environment-friendly substitute for xylene with regards to tissue processing. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This research aims to pinpoint key biomarkers and immunological infiltration of idiopathic pulmonary fibrosis (IPF) through bioinformatics analysis. METHODS: From the GEO database, 12 gene expression profiles were obtained. The LIMMA tool in Bioconductor accustomed to identify the genes that are expressed differently (DEGs), and analyses of functional enrichment were performed. A protein-protein interaction network (PPI) was constructed using STRING and Cytoscape, and a modular analysis was performed. Analysis of the immunological infiltration of lung tissue between IPF and healthy groups was done using the CIBERSORTx method. RESULTS: 11,130 genes with differential expression (including 7,492 up-regulated and 3,638 down-regulated) were found. The selected up-regulated DEGs were mainly involved in the progression of pulmonary fibrosis and the selected down-regulated DEGs maintain the relative stability of intracellular microenvironment, according to functional enrichment analysis. KEGG enrichment analysis revealed that up-regulated DEGs were primarily abundant in the PI3K-Akt signaling mechanism, whereas down-regulated DEGs were associated with cancer pathways. The most significant modules involving 8 hub genes were found after the PPI network was analyzed. IPF lung tissue had a greater percentage of B memory cells, plasma cells, T cells follicular helper, T cells regulatory, T cells gamma delta, macrophages M0 and resting mast cells. while a relatively low proportion of T cells CD4 memory resting, NK cells resting and neutrophils. CONCLUSION: This research demonstrates the differences of hub genes and immunological infiltration in IPF. [ABSTRACT FROM AUTHOR]

The glycocalyx (GCX) covers the luminal surface of blood vessels and regulates vascular permeability. As GCX degradation predicts various types of vasculopathy, confirming the presence of this structure is useful for diagnosis. Since the GCX layer is very fragile, careful fixation is necessary to preserve its structure. We explored appropriate and feasible methodologies for visualizing the GCX layer using lung tissue specimens excised from anesthetized mice. Each specimen was degassed and immersed in Alcian blue (ALB) fixative solution, and then observed using electron microscopy. Specimens from septic mice were prepared as negative GCX controls. Using these immersion-fixed specimens, the GCX layer was successfully observed using both transmission and scanning electron microscopy; these observations were similar to those obtained using the conventional method of lanthanum perfusion fixation. Spherical aggregates of GCX were observed in the septic mouse specimens, and the GCX density was lower in the septic specimens than in the non-septic specimens. Of note, the presently reported methodology reduced the specimen preparation time from 6 to 2 days. We, therefore, concluded that our novel method could be applied to human lung specimens and could potentially contribute to the further elucidation of vasculopathies. [ABSTRACT FROM AUTHOR]

In sporadic idiopathic pulmonary fibrosis (sIPF) and pulmonary fibrosis caused by a mutation in telomere (TRG-PF) or surfactant related genes (SRG-PF), there are a number of aberrant cellular processes known that can lead to fibrogenesis. We investigated whether RNA expression of genes involved in these processes differed between sIPF, TRG-PF, and SRG-PF and whether expression levels were associated with survival. RNA expression of 28 genes was measured in lung biopsies of 26 sIPF, 17 TRG-PF, and 6 SRG-PF patients. Significant differences in RNA expression of TGFBR2 (p = 0.02) and SFTPA2 (p = 0.02) were found between sIPF, TRG-PF, and SRG-PF. Patients with low (

Abstract Solitary respiratory papilloma is a rare epithelial tumour that can be categorized into multiple subtypes. The glandular type (Glandular papilloma, GP) is the rarest. Most GP occurs in the proximal airways and is only rarely found in the lung parenchyma. In this article, we reported a case of GP in lung parenchyma.

Hydrogen sulfide (H2S) is a typical odour compound mainly causing respiratory and central nervous system symptoms. However, the immunotoxicity of inhaled H2S and the underlying mechanisms remain largely unknown. In this study, a low-dose inhalation exposure to H2S was arranged to observe inflammatory response and immunotoxicity in lung tissue of rats. Low concentrations of H2S exposure affected the immune level of pulmonary tissue and peripheral blood. Significant pathological changes in lung tissue in the exposure group were observed. At low concentration, H2S not only induced the upregulation of AQP-4 and MMP-9 expression but also stimulated immune responses, initiating various anti-inflammatory and inflammatory factors, altering tissue homeostatic environments. The TNF and chemokine signaling pathway played an important role which can promote the deterioration of pulmonary inflammatory processes and lead to lung injury and fibrosis. Excessive immune response causes an inflammatory effect and blood-gas barrier damage. These data will be of value in evaluating future occupational health risks and providing technical support for the further development of reliable, sensitive, and easy-to-use screening indicators of exposure injury.

Solitary respiratory papilloma is a rare epithelial tumour that can be categorized into multiple subtypes. The glandular type (Glandular papilloma, GP) is the rarest. Most GP occurs in the proximal airways and is only rarely found in the lung parenchyma. In this article, we reported a case of GP in lung parenchyma. [ABSTRACT FROM AUTHOR]

Intense exercise training is associated with Lung inflammation. Fasl protein on the cell surface is responsible for the initiation of the inflammatory response that finally leads to cell death at the site of inflammation, and can be interpreted as Fasl induced apoptosis. Therefore, the aim of this study was to investigate the effects of increasing and intense interval exercise training on Fasl levels of mature rat lungs. 30 rats within three weeks of birth with mean weight 68±9 g were randomly divided into three basic, control, and exercise groups. Increasing interval training for 6 sessions per week, each session 30 minutes at a speed of 15 to 70 meters per min was employed and Fasl levels were measured using the kitby Elisa method. The data were analyzed with two-way ANOVA and LSD test was done at p≤0.05 significant level. The results showed that Fasl protein levels in the interval training group compared to baseline group increased by 23.75 % and was significant (p≤0/05). However, although the amount of this protein in the interval training group compared to the control group was high, this value was not significant. In addition, Fasl protein levels in the control group compared to the baseline group increased by13.58 % and was significant (p≤0.05). The findings indicated that intense and prolonged exercise training causes damage of the respiratory tract, and in turn, leads to the increased levels of Fasl.

Microplastics (MPs) have received a lot of attention and have been detected in multiple environmental matrices as a new environmental hazard, but studies on human internal exposure to MPs are limited. Here, we collected lung tissue samples from 12 nonsmoking patients to evaluate the characteristics of MPs in human lung tissues using an Agilent 8700 laser infrared imaging spectrometer and scanning electron microscopy. We detected 108 MPs covering 12 types in the lung tissue samples, with a median concentration of 2.19 particles/g. Most of the MPs (88.89%) were sized between 20 to 100 μm. Polypropylene accounts for 34.26% of the MPs in the lung tissues, followed by polyethylene terephthalate (21.30%) and polystyrene (8.33%). Compared with males and those living far from a major road (≥300 m), females and those living near the main road (<300 m) had higher levels of MPs in lung tissues, which positively correlated with platelet (PLT), thrombocytocrit, fibrinogen (FIB), and negatively related with direct bilirubin (DB). These findings help confirm the presence in the respiratory system and suggest the potential sources and health effects of inhaled MPs. [ABSTRACT FROM AUTHOR]

PURPOSE The purpose of this study was to investigate the effects of hyperventilation in the presence of fine particulate matter (PM2.5) on inflammatory and apoptotic responses in the lungs of mice during a single bout of aerobic exercise. METHODS The FVB/N mice were housed in a controlled SPF room and randomly divided into four groups: control (CON, n=7), fine particulate matter exposure (PM, n=7), PM and exercise (PME, n=7), and exercise only (EX, n=7). Acute PM exposure and/or aerobic treadmill exercise were undertaken according to the groups using a specially designed PM treadmill chamber. RESULTS Protein expression and phosphorylation of p65 NF-kB in mouse lungs were significantly increased by acute exercise, but not by PM exposure. Basal protein levels and phosphorylation of MAPKs (p38, ERK, and JNK) were significantly increased in the PME group, but were lower in the PM and EX groups. Although the percentage of collagen fibers in lung tissue was not affected by PM exposure, the expression of pro- and antiapoptotic factors BAX, BID, and Bcl-2 was significantly elevated by inhalation of PM during exercise. CONCLUSIONS In this study, the MAPKs family was activated by excessive PM inhalation during exercise and similar changes in apoptosis-related signaling were observed. This suggests that even a single bout of inhalation of fine particulate matter during exercise can affect factors associated with inflammation and cell death.

We advanced a novel model to calculate viscoelastic lung compliance and airflow resistance in presence of mucus, accounting for the quasi‐linear viscoelastic stress–strain response of the parenchyma (alveoli) tissue. We adapted a continuum‐based numerical modeling approach for the lung, integrating the fluid mechanics of the airflow within individual generations of the bronchi and alveoli. The model accounts for elasticity of the deformable bronchioles, resistance to airflow due to the presence of mucus within the bronchioles, and subsequent mucus flow. Simulated quasi‐dynamic inhalation and expiration cycles were used to characterize the net compliance and resistance of the lung, considering the rheology of the mucus and viscoelastic properties of the parenchyma tissue. The structure and material properties of the lung were identified to have an important contribution to the lung compliance and airflow resistance. The secondary objective of this work was to assess whether a higher frequency and smaller volume of harmonic air flow rate compared to a normal ventilator breathing cycle enhanced mucus outflow. Results predict, lower mucus viscosity and higher excitation frequency of breathing are favorable for the flow of mucus up the bronchi tree, towards the trachea. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by irreversible lung tissue damage. Novel regenerative strategies are urgently awaited. Cultured mesenchymal stem/stromal cells (MSCs) have shown promising results in experimental models of COPD, but differences between sources may impact on their potential use in therapeutic strategies in patients. Aim To assess the transcriptome of lung-derived MSCs (LMSCs), bone marrow-derived MSCs (BM-MSC) and adipose-derived MSCs (AD-MSCs) from COPD patients and non-COPD controls. Methods We studied differences in gene expression profiles between the MSC-subtypes, as well as between COPD and control using RNA sequencing (RNA-seq). Results We show that besides heterogeneity between donors, MSCs from different sources have strongly divergent gene signatures. The growth factors FGF10 and HGF were predominantly expressed in LMSCs. MSCs from all sources displayed altered expression profiles in COPD, with most pronounced significantly up- and downregulated genes in MSCs from adipose tissue. Pathway analysis revealed that the most differentially expressed genes in COPD-derived AD-MSCs are involved in extracellular matrix (ECM) binding and expression. In LMSCs, the gene that differed most strongly between COPD and control was CSGALNACT1, an ECM modulating gene. Conclusion Autologous MSCs from COPD patients display abnormalities with respect to their transcriptome, which were surprisingly most profound in MSCs from extrapulmonary sources. LMSCs may be optimally equipped for lung tissue repair because of the expression of specific growth factor genes.

We studied changes in the ultrastructure of brain tissues - medulla oblongata and striatum, as well as lung and heart tissues in experimental parkinsonism caused by the action of rotenone, which was administered once or for 2 weeks. It has been shown that during the development of a Parkinson-like state the ultrastructure of tissues disturbance, the development of mitochondrial and endothelial dysfunction is observed not only in parts of the brain, but also in other tissues of the body. Mitochondrial dysfunction is significantly expressed in the medulla oblongata, as evidenced by, firstly, a decrease in the total number of mitochondria by 35.7%, and secondly, damage to their ultrastructure in more than 40% of organelles. Endothelial dysfunction was indicated by hyperhydration of the blood-brain barrier. In the tissue of the striatum, the indicated changes were insignificant, instead, a compensatory restoration of dynamic processes in the mitochondrial apparatus, in particular fission-fusion processes, was observed. In the myocardium, there were also significant changes in the ultrastructure, this indicated the development of both mitochondrial and endothelial dysfunctions. As well as in the medulla oblongata tissue, about 40% of mitochondria were found to be damaged, although it should be noted that although not pronounced, but still reliable (by 12.6%) activation of mitochondrial morphogenesis was observed. The histohematal barrier, in particular its endothelial layer, thinned due to destructive processes. Violations of the ultrastructure were also observed in the lung tissue. Significant changes in the mitochondrial apparatus with damage to the mitochondrial structure were revealed. However, the percentage of structurally damaged organelles was significantly (almost 2 times) lower than in the myocardium (reached only 25%). The thickness of the endothelial layer of the air barrier increased by an average of 30%. In tissues where mitochondrial and endothelial dysfunction were less pronounced during longterm administration of rotenone, adaptive changes begin to form, which are probably also observed in people with Parkinson's disease, which enables them to adapt to the existing disease. [ABSTRACT FROM AUTHOR]

Interstitial lung tissue diseases (pulmonary fibrosis) are accompanied by a decrease in thrombopoiesis. Stem cells are capable of differentiating into other cell types, making them a valuable material for veterinary cellular regenerative therapy. The purpose of the research -- to explore changes in platelet counts in laboratory rats with experimental pulmonary fibrosis under the influence of stem cells. The research was performed on female Wistar rats, in which pulmonary fibrosis was modelled using a single transthoracic injection of bleomycin hydrochloride solution. Allogeneic mesenchymal stem cells were used to stimulate recovery processes in pathologically altered lung tissue, which were administered by different routes, and, for comparison, the conventional method of treatment. The presented results of the effect of transplanted allogeneic bone marrow mesenchymal stem cells indicate a significant change in the number and size of platelets in rats with experimental pulmonary fibrosis and an increase in the activity of regenerative processes in damaged tissues. In experimental animals, a significant increase in the number of platelets and their size was found after using allogeneic mesenchymal stem cells compared to similar data in control group animals. In addition, in the blood of animals of the experimental group, which were transplanted with mesenchymal stem cells transthoracically (directly into the lung tissue), there was a higher platelet activity than in animals with intravenous injection of mesenchymal stem cells. Platelet activation indicates an improvement in the regenerative capacity of damaged lung tissue under the influence of mesenchymal stem cells. Thus, transplanted mesenchymal stem cells stimulate platelet activity and regenerative processes in pathologically altered lung tissue in experimental fibrosis, which can be used as one of the effective methods of treating animals with this type of pathology [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD), a common respiratory disease, can be divided into stable phase and acute exacerbation phase (AECOPD) and is characterized by inflammation and hyper-immunity. Methylation of N6-methyladenosine (m6A) is an epigenetic modification that regulates the expression and functions of genes by influencing post-transcriptional RNA modifications. Its influence on the immune regulation mechanism has attracted great attention. Herein, we present the m6Amethylomic landscape and observe how the methylation of m6A participates in the pathological process of COPD. The m6A modification of 430 genes increased and that of 3995 genes decreased in the lung tissues of mice with stable COPD. The lung tissues of mice with AECOPD exhibited 740 genes with hypermethylated m6A peak and 1373 genes with low m6A peak. These differentially methylated genes participated in signaling pathways related to immune functions. To further clarify the expression levels of differentially methylated genes, RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-sequencing data were jointly analyzed. In the stable COPD group, 119 hypermethylated mRNAs (82 upregulated and 37 downregulated mRNAs) and 867 hypomethylated mRNAs (419 upregulated and 448 downregulated mRNAs) were differentially expressed. In the AECOPD group, 87 hypermethylated mRNAs (71 upregulated and 16 downregulated mRNAs) and 358 hypomethylated mRNAs (115 upregulated and 243 downregulated mRNAs) showed differential expression. Many mRNAs were related to immune function and inflammation. Together, this study provides important evidence on the role of RNA methylation of m6A in COPD. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is one of the deadliest diseases worldwide and represents an impending burden on the healthcare system. Despite increasing attention, the mechanisms underlying tumorigenesis in cancer-related diseases such as COPD remain unclear, making novel biomarkers necessary to improve lung cancer early diagnosis. MicroRNAs (miRNAs) are short non-coding RNA that interfere with several pathways and can act as oncogenes or tumor suppressors. This study aimed to compare miRNA lung expression between subjects with NSCLC and COPD and healthy controls to obtain the miRNA expression profile by analyzing shared pathways. Lung specimens were collected from a prospective cohort of 21 sex-matched subjects to determine the tissue miRNA expression of hsa-miR-34a-5p, 33a-5p, 149-3p, 197-3p, 199-5p, and 320a-3p by RT-PCR. In addition, an in silico prediction of miRNA target genes linked to cancer was performed. We found a specific trend for has-miR-149-3p, 197-3p, and 34a-5p in NSCLC, suggesting their possible role as an index of the tumor microenvironment. Moreover, we identified novel miRNA targets, such as the Cyclin-Dependent Kinase (CDK) family, linked to carcinogenesis by in silico analysis. In conclusion. this study identified lung miRNA signatures related to the tumorigenic microenvironment, suggesting their possible role in improving the evaluation of lung cancer onset. [ABSTRACT FROM AUTHOR]

The microscopic observation of lung tissue is challenging due to its fragile nature. Xylene and isopropanol are common tissue-clearing reagents used before paraffin embedding, yet no studies have compared these two reagents in lung tissue processing. Due to the well-known health risks xylene could introduce to operators, as well as its environmental hazards, it has long been desired that a less harmful alternative to xylene with the same staining effects be introduced. Thus, we systematically assessed the efficacy of isopropanol as a substitution for xylene. Lung tissue obtained from diseased donors and explanted lungs from recipients were processed simultaneously using either xylene or isopropanol prior to paraffin embedding. Scoring of the overall staining quality after H&E staining, along with the ease of sectioning, was compared systematically. Fluorescent staining was performed to explore alveolar morphology and the overall lectin fluorescence signal between groups. To understand differences in antibody staining, the signal-to-noise ratio (SNR) of smooth muscle actin (SMA) and elastin was examined. No difference was observed with regard to ease of sectioning, staining quality, alveolar circularity, alveolar wall thickness or the SNR between slides processed with xylene or isopropanol. This study demonstrated comparable outcomes of isopropanol and xylene in lung tissue processing, suggesting isopropanol as a more favorable, operator- and environment-friendly substitute for xylene with regards to tissue processing.

Hypertensive individuals taking anti‐hypertensive drugs from renin‐angiotensin system inhibitors may exhibit a more severe evolution of the disease when contracting the SARS‐CoV‐2 virus (COVID‐19 disease) due to potential increases in ACE2 expression. The study investigated ACE1 and ACE2 axes and hydroxychloroquine in the lungs and adipose tissue of male and female normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHRs). SHRs were treated with losartan (10 mg/kg/day) or captopril (10 mg/kg/day) for 14 days or 7 days with hydroxychloroquine (200 mg/kg/day) in drinking water. WKY rats were also treated for 7 days with hydroxychloroquine. Blood pressure (BP), protein, and mRNA expression of ACE1 and ACE2 were analyzed in serum, adipose, and lung tissues. Losartan and captopril reduced BP in both sexes in SHR, whereas hydroxychloroquine increased BP in WKY rats. Losartan reduced ACE2 in serum and lungs in both sexes and in adipose tissue of male SHRs. Captopril decreased ACE2 protein in the lung of females and in adipose tissue in both sexes of SHRs. Hydroxychloroquine decreased ACE1 and ACE2 proteins in the lungs in both sexes and adipose tissue in male SHRs. In female WKY rats, ACE2 protein was lower only in the lungs and adipose tissue. Losartan effectively inhibited ACE2 in male and captopril in female SHRs. Hydroxychloroquine inhibited ACE2 in male SHRs and female WKY rats. These results further our understanding of the ACE2 mechanism in patients under renin‐angiotensin anti‐hypertensive therapy and in many trials using hydroxychloroquine for COVID‐19 treatment and potential sex differences in response to drug treatment. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible lung tissue damage. Novel regenerative strategies are urgently awaited. Cultured mesenchymal stem/stromal cells (MSCs) have shown promising results in experimental models of COPD, but differences between sources may impact on their potential use in therapeutic strategies in patients. Aim: To assess the transcriptome of lung-derived MSCs (LMSCs), bone marrow-derived MSCs (BM-MSC) and adipose-derived MSCs (AD-MSCs) from COPD patients and non-COPD controls. Methods: We studied differences in gene expression profiles between the MSC-subtypes, as well as between COPD and control using RNA sequencing (RNA-seq). Results: We show that besides heterogeneity between donors, MSCs from different sources have strongly divergent gene signatures. The growth factors FGF10 and HGF were predominantly expressed in LMSCs. MSCs from all sources displayed altered expression profiles in COPD, with most pronounced significantly up- and downregulated genes in MSCs from adipose tissue. Pathway analysis revealed that the most differentially expressed genes in COPD-derived AD-MSCs are involved in extracellular matrix (ECM) binding and expression. In LMSCs, the gene that differed most strongly between COPD and control was CSGALNACT1, an ECM modulating gene. Conclusion: Autologous MSCs from COPD patients display abnormalities with respect to their transcriptome, which were surprisingly most profound in MSCs from extrapulmonary sources. LMSCs may be optimally equipped for lung tissue repair because of the expression of specific growth factor genes. [ABSTRACT FROM AUTHOR]

The increase of tissue transparency through sequential optical immersion clearing treatments and treatment reversibility have high interest for clinical applications. To evaluate the clearing reversibility in a broad spectral range and the magnitude of the transparency created by a second treatment, the present study consisted on measuring the spectral collimated transmittance of lung tissues during a sequence of two treatments with electronic cigarette (e‐cig) fluid, which was intercalated with an immersion in saline. The saline immersion clearly reverted the clearing effect in the lung tissue in the spectral range between 220 and 1000 nm. By a later application of a second treatment with the e‐cig fluid, the magnitude of the optical clearing effect was observed to be about the double as the one observed in the first treatment, showing that the molecules of the optical clearing agent might have converted some bound water into mobile water during the first treatment. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Beijing University of Technology is the property of Journal of Beijing University of Technology, Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Micro-scale models of lung tissue have been employed by researchers to investigate alveolar mechanics; however, they have been limited by the lack of biofidelic material properties for the alveolar wall. To address this challenge, a finite element model of an alveolar cluster was developed comprising a tetrakaidecahedron array with the nominal characteristics of human alveolar structure. Lung expansion was simulated in the model by prescribing a pressure and monitoring the volume, to produce a pressure-volume (PV) response that could be compared to experimental PV data. The alveolar wall properties in the model were optimized to match experimental PV response of lungs filled with saline, to eliminate surface tension effects and isolate the alveolar wall tissue response. When simulated in uniaxial tension, the model was in agreement with reported experimental properties of uniaxial tension on excised lung tissue. The work presented herein was able to link micro-scale alveolar response to two disparate macroscopic experimental datasets (stress-stretch and PV response of lung) and presents hyperelastic properties of the alveolar wall for use in alveolar scale finite element models and multi-scale models. Future research will incorporate surface tension effects, and investigate alveolar injury mechanisms. • Demonstrates agreement between stress-strain and pressure-volume data of lungs using alveolar finite element model. • Sensitivity study suggests an initial unloaded volume for the alveolar wall tissue of approximately 30 %TLC. • Presents hyperelastic properties of alveolar wall for use in alveolar models, and to inform multi-scale models of lung. [ABSTRACT FROM AUTHOR]

Microplastics (MPs) have received a lot of attention and have been detected in multiple environmental matrices as a new environmental hazard, but studies on human internal exposure to MPs are limited. Here, we collected lung tissue samples from 12 nonsmoking patients to evaluate the characteristics of MPs in human lung tissues using an Agilent 8700 laser infrared imaging spectrometer and scanning electron microscopy. We detected 108 MPs covering 12 types in the lung tissue samples, with a median concentration of 2.19 particles/g. Most of the MPs (88.89%) were sized between 20 to 100 μm. Polypropylene accounts for 34.26% of the MPs in the lung tissues, followed by polyethylene terephthalate (21.30%) and polystyrene (8.33%). Compared with males and those living far from a major road (≥300 m), females and those living near the main road (

Abstract Hypertensive individuals taking anti‐hypertensive drugs from renin‐angiotensin system inhibitors may exhibit a more severe evolution of the disease when contracting the SARS‐CoV‐2 virus (COVID‐19 disease) due to potential increases in ACE2 expression. The study investigated ACE1 and ACE2 axes and hydroxychloroquine in the lungs and adipose tissue of male and female normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHRs). SHRs were treated with losartan (10 mg/kg/day) or captopril (10 mg/kg/day) for 14 days or 7 days with hydroxychloroquine (200 mg/kg/day) in drinking water. WKY rats were also treated for 7 days with hydroxychloroquine. Blood pressure (BP), protein, and mRNA expression of ACE1 and ACE2 were analyzed in serum, adipose, and lung tissues. Losartan and captopril reduced BP in both sexes in SHR, whereas hydroxychloroquine increased BP in WKY rats. Losartan reduced ACE2 in serum and lungs in both sexes and in adipose tissue of male SHRs. Captopril decreased ACE2 protein in the lung of females and in adipose tissue in both sexes of SHRs. Hydroxychloroquine decreased ACE1 and ACE2 proteins in the lungs in both sexes and adipose tissue in male SHRs. In female WKY rats, ACE2 protein was lower only in the lungs and adipose tissue. Losartan effectively inhibited ACE2 in male and captopril in female SHRs. Hydroxychloroquine inhibited ACE2 in male SHRs and female WKY rats. These results further our understanding of the ACE2 mechanism in patients under renin‐angiotensin anti‐hypertensive therapy and in many trials using hydroxychloroquine for COVID‐19 treatment and potential sex differences in response to drug treatment.

Copyright of China Tropical Medicine is the property of China Tropical Medicine Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Metrics used in spirometry caught on in respiratory medicine not only because they provide information of clinical importance but also because of a keen understanding of what is being measured. The forced expiratory volume in 1 s (FEV1), for example, is the maximal volume of air that can be expelled during the first second of a forced expiratory maneuver starting from a lung inflated to total lung capacity (TLC). Although it represents a very gross measurement of lung function, it is now used to guide the diagnosis and management of many lung disorders. Metrics used in oscillometry are not as concrete. Resistance, for example, has several connotations and its proper meaning in the context of a lung probed by an external device is not always intuitive. I think that the popularization of oscillometry and its firm implementation in respiratory guidelines starts with a keen understanding of what exactly is being measured. This review is an attempt to clearly explain the basic metrics of oscillometry. In my opinion, the fundamentals of oscillometry can be understood using a simple example of an excised strip of lung tissue subjected to a sinusoidal strain. The key notion is to divide the sinusoidal reacting force from the tissue strip into two sinusoids, one in phase with the strain and one preceding the strain by exactly a quarter of a cycle. Similar notions can then be applied to a whole lung subjected to a sinusoidal flow imposed at the mouth by an external device to understand basic metrics of oscillometry, including resistance, elastance, impedance, inertance, reactance and resonant frequency. [ABSTRACT FROM AUTHOR]

Macrophages are vital in maintaining tissue homeostasis in the lungs by modulating and regulating immune responses. Based on different origins and anatomical locations, macrophages in the lungs are categorized into alveolar macrophages, interstitial macrophages, perivascular macrophages, and inflammatory macrophages. Alveolar macrophages are located in the alveolar spaces and are primarily responsible for maintaining alveolar surfactant homeostasis, defending against pathogens and regulating immune responses. Interstitial macrophages can maintain homeostasis, regulate immunity and anti-inflammation in the lung tissue. Perivascular macrophages play a crucial role in inhibiting lung inflammation, improving pulmonary fibrosis, and regulating lung tumor progression due to antigen-presenting and immunomodulatory effects. Inflammatory macrophages, which are differentiated from monocytes during inflammation, regulate the inflammatory process. This article reviews the origins of various subpopulations of macro-phages in the lung tissue and their physiological and pathological functions as well as discusses the underlying mechanisms and potential therapeutic targets.

Histophilus somni is an important causative agent of bovine respiratory disease complex. Here, we report the complete genome sequence of a Histophilus somni strain 91, which was isolated from a pneumonic lung tissue sample collected from a beef calf., Competing Interests: The authors declare no conflict of interest.

Blood-based, observational, and cross-sectional epidemiological studies suggest that air pollutant exposures alter biological aging. In a single-blinded randomized crossover human experiment of 17 volunteers, we examined the effect of randomized 2-h controlled air pollution exposures on respiratory tissue epigenetic aging. Bronchial epithelial cell DNA methylation 24 h post-exposure was measured using the HumanMethylation450K BeadChip, and there was a minimum 2-week washout period between exposures. All 17 volunteers were exposed to ozone, but only 13 were exposed to diesel exhaust. Horvath DNAmAge [Pearson coefficient (r) = 0.64; median absolute error (MAE) = 2.7 years], GrimAge (r = 0.81; MAE = 13 years), and DNAm Telomere Length (DNAmTL) (r = -0.65) were strongly correlated with chronological age in this tissue. Compared to clean air, ozone exposure was associated with longer DNAmTL (median difference 0.11 kb, Fisher's exact P -value = .036). This randomized trial suggests a weak relationship of ozone exposure with DNAmTL in target respiratory cells. Still, causal relationships with long-term exposures need to be evaluated., Competing Interests: C.W.C. is a scientific advisor for the Clock Foundation. The Clock Foundation had no role in any aspect of this work. The remaining authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press.)

Metrics used in spirometry caught on in respiratory medicine not only because they provide information of clinical importance but also because of a keen understanding of what is being measured. The forced expiratory volume in 1 s (FEV1), for example, is the maximal volume of air that can be expelled during the first second of a forced expiratory maneuver starting from a lung inflated to total lung capacity (TLC). Although it represents a very gross measurement of lung function, it is now used to guide the diagnosis and management of many lung disorders. Metrics used in oscillometry are not as concrete. Resistance, for example, has several connotations and its proper meaning in the context of a lung probed by an external device is not always intuitive. I think that the popularization of oscillometry and its firm implementation in respiratory guidelines starts with a keen understanding of what exactly is being measured. This review is an attempt to clearly explain the basic metrics of oscillometry. In my opinion, the fundamentals of oscillometry can be understood using a simple example of an excised strip of lung tissue subjected to a sinusoidal strain. The key notion is to divide the sinusoidal reacting force from the tissue strip into two sinusoids, one in phase with the strain and one preceding the strain by exactly a quarter of a cycle. Similar notions can then be applied to a whole lung subjected to a sinusoidal flow imposed at the mouth by an external device to understand basic metrics of oscillometry, including resistance, elastance, impedance, inertance, reactance and resonant frequency.

Optical clearing of the lung tissue aims to make it more transparent to light by minimizing light scattering, thus allowing reconstruction of the three-dimensional structure of the tissue with a much better resolution. This is of great importance for monitoring of viral infection impact on the alveolar structure of the tissue and oxygen transport. Optical clearing agents (OCAs) can provide not only lesser light scattering of tissue components but also may influence the molecular transport function of the alveolar membrane. Air-filled lungs present significant challenges for optical imaging including optical coherence tomography (OCT), confocal and two-photon microscopy, and Raman spectroscopy, because of the large refractive-index mismatch between alveoli walls and the enclosed air-filled region. During OCT imaging, the light is strongly backscattered at each air–tissue interface, such that image reconstruction is typically limited to a single alveolus. At the same time, the filling of these cavities with an OCA, to which water (physiological solution) can also be attributed since its refractive index is much higher than that of air will lead to much better tissue optical transmittance. This review presents general principles and advances in the field of tissue optical clearing (TOC) technology, OCA delivery mechanisms in lung tissue, studies of the impact of microbial and viral infections on tissue response, and antimicrobial and antiviral photodynamic therapies using methylene blue (MB) and indocyanine green (ICG) dyes as photosensitizers. [ABSTRACT FROM AUTHOR]

Background: In order to study the effect of bifurcation vessels parameters on the temperature field and coagulation zone of microwave ablation on lung tissue. Methods: The finite element method was used to establish the simulation model. The angle of bifurcation vessel model was 60°. The position of the antenna and the main blood vessel are parallel, and the distance between them was 5, 10 and 15 mm, respectively. Temperature field distribution was obtained at 2450 MHz, 50 W and 300 s. The blood flow velocity was set to 0.1 and 0.2 m/s. Results: The results showed when the antenna was 5 mm away from the bifurcation vessel and the velocity was 0.1 m/s, the position of x = 8.4 mm achieved the complete necrosis at 220 s, while the fraction of necrotic tissue at the symmetry point x = 1.6 mm was 0.2 at 300 s. For the distance was 10 mm and the velocity was 0.1 m/s, the fraction of necrotic tissue at x = 3 mm that near the bifurcation vessel was 0.53 and was 0.69 at the symmetry point x = 17 mm. When the antenna is 15 mm away from the vessel, the fraction of necrotic tissue of symmetrical points on both sides of the antenna obtained after ablation were the same. Conclusions: The distance between the antenna and the bifurcation vessel over 15 mm, the blood flow has no effect on the coagulation zone. Besides, the distance between bifurcation vessel and antenna possesses a greater influence on the temperature distribution and coagulation zone than the blood flow velocity. [ABSTRACT FROM AUTHOR]

Simple Summary: Tackling and curing cancer is still one of the most important challenges of biomedical research. Lung cancer is among the most diverse and lethal types, therefore identifying alterations in proteins participating in events leading to this disease is crucial. By analyzing and comparing the tissue proteomics profile of small cell lung cancer, as well as non-small cell lung cancer (adenocarcinoma, squamous cell carcinoma, large cell carcinoma) subtypes, following on-surface tryptic digestion, we aimed to identify the key dysregulated pathways. Proteins altered between cancerous and respective adjacent normal tissue were determined to reveal common and lung cancer type-specific changes. These proteins can contribute to a more precise classification of lung cancer and, following validation, can further improve the currently available diagnostic panels. Lung cancer is the leading cause of tumor-related mortality, therefore significant effort is directed towards understanding molecular alterations occurring at the origin of the disease to improve current treatment options. The aim of our pilot-scale study was to carry out a detailed proteomic analysis of formalin-fixed paraffin-embedded tissue sections from patients with small cell or non-small cell lung cancer (adenocarcinoma, squamous cell carcinoma, and large cell carcinoma). Tissue surface digestion was performed on relatively small cancerous and tumor-adjacent normal regions and differentially expressed proteins were identified using label-free quantitative mass spectrometry and subsequent statistical analysis. Principal component analysis clearly distinguished cancerous and cancer adjacent normal samples, while the four lung cancer types investigated had distinct molecular profiles and gene set enrichment analysis revealed specific dysregulated biological processes as well. Furthermore, proteins with altered expression unique to a specific lung cancer type were identified and could be the targets of future studies. [ABSTRACT FROM AUTHOR]

Background: It is recommended for each set of radiation data and algorithm that subtle deliberation is done regarding dose calculation accuracy. Knowing the errors in dose calculation for each treatment plan will result in an accurate estimate of the actual dose achieved by the tumor. Objective: This study aims to evaluate the equivalent path length (EPL) and equivalent tissue air ratio (ETAR) algorithms in radiation dose calculation.Material and Methods: In this experimental study, the TEC-DOC 1583 guideline was used. Measurements and calculations were obtained for each algorithm at specific points in thorax CIRS phantom for 6 and 18 MVs and results were compared. Results: In the EPL, calculations were in agreement with measurements for 27 points and differences between them ranged from 0.1% to 10.4% at 6 MV. The calculations were in agreement with measurements for 21 points and differences between them ranged from 0.4% to 13% at 18 MV. In ETAR, calculations were also in consistent with measurements for 21 points, and differences between them ranged from 0.1% to 9% at 6 MV. Moreover, for 18 MV, the calculations were in agreement with measurements for 17 points and differences between them ranged from 0% to 11%. Conclusion: For the EPL algorithm, more dose points were in consistent with acceptance criteria. The errors in the ETAR were 1% to 2% less than the EPL. The greatest calculation error occurs in low-density lung tissue with inhomogeneities or in high-density bone. Errors were larger in shallow depths. The error in higher energy was more than low energy beam.

Abstract Objective Human precision cut lung slices (PCLS) are widely used as an ex vivo model system for drug discovery and development of new therapies. PCLS reflect the functional heterogeneity of lung tissue and possess relevant lung cell types. We thus determined the use of PCLS in studying non-coding RNAs notably miRNAs, which are important gene regulatory molecules. Since miRNAs play key role as mediators of respiratory diseases, they can serve as valuable prognostic or diagnostic biomarkers, and in therapeutic interventions, of lung diseases. A technical limitation though is the vast amount of agarose in PCLS which impedes (mi)RNA extraction by standard procedures. Here we modified our recently published protocol for RNA isolation from PCLS to enable miRNA readouts. Results The modified method relies on the separation of lysis and precipitation steps, and a clean-up procedure with specific magnetic beads. We obtained successfully quality miRNA amenable for downstream applications such as RTqPCR and whole transcriptome miRNA analysis. Comparison of miRNA profiles in PCLS with published data from human lung, identified all important miRNAs regulated in IPF, COPD, asthma or lung cancer. Therefore, this shows suitability of the method for analyzing miRNA targets and biomarkers in the valuable human PCLS model.

Methylation modification of small RNAs, including miRNA, piRNA, and tsRNA, is critical for small RNA biogenesis and biological function. Methylation of individual small RNA can be defined by liquid chromatography-coupled with mass spectrometry (LC-MS/MS). However, LC-MS/MS analysis requires a high purity of individual small RNA. Due to the difficulty of purifying specific small RNA from tissues or cells, the progress in characterizing small RNA methylation by LC-MS/MS is limited. Here, we report a novel method that can efficiently purify small RNA from human tissues for LC-MS/MS analysis. This method includes two steps: 1) pull down the target small RNA by incubating total small RNAs (18–24 nt) extracted from human tissues with a biotinylated antisense oligonucleotide of the target small RNA, followed by capturing the binding duplex of biotinylated antisense and small RNA via streptavidin magnetic beads, and 2) protect the target small RNA by pairing it with a single-strand DNA, which sequence is complementary to the target small RNA, to form a DNA/RNA hybrid double-strand, followed by sequential digestion with exonuclease I, nuclease S1, and DNase I, respectively. Furthermore, employing a mixture of four pairs of synthetic methylated and non-methylated small RNAs, we further refined this two-step method by optimizing the nuclease S1 treatment condition. With this method, we successfully purified miR-21-5p, miR-26-5p, piR-020485, and tsRNA from human lung and sperm tissue samples and analyzed their 2′-O-methylation modification at the 3′-end by LC-MS/MS.

ABSTRACT The influenza virus (IAV) is a major cause of respiratory disease, with significant infection increases in pandemic years. Vaccines are a mainstay of IAV prevention but are complicated by IAV’s vast strain diversity and manufacturing and vaccine uptake limitations. While antivirals may be used for treatment of IAV, they are most effective in early stages of the infection, and several virus strains have become drug resistant. Therefore, there is a need for advances in IAV treatment, especially host-directed therapeutics. Given the spatial dynamics of IAV infection and the relationship between viral spatial distribution and disease severity, a spatial approach is necessary to expand our understanding of IAV pathogenesis. We used spatial metabolomics to address this issue. Spatial metabolomics combines liquid chromatography-tandem mass spectrometry of metabolites extracted from systematic organ sections, 3D models, and computational techniques to develop spatial models of metabolite location and their role in organ function and disease pathogenesis. In this project, we analyzed serum and systematically sectioned lung tissue samples from uninfected or infected mice. Spatial mapping of sites of metabolic perturbations revealed significantly lower metabolic perturbation in the trachea compared to other lung tissue sites. Using random forest machine learning, we identified metabolites that responded differently in each lung position based on infection, including specific amino acids, lipids and lipid-like molecules, and nucleosides. These results support the implementation of spatial metabolomics to understand metabolic changes upon respiratory virus infection. IMPORTANCE The influenza virus is a major health concern. Over 1 billion people become infected annually despite the wide distribution of vaccines, and antiviral agents are insufficient to address current clinical needs. In this study, we used spatial metabolomics to understand changes in the lung and serum metabolome of mice infected with influenza A virus compared to uninfected controls. We determined metabolites altered by infection in specific lung tissue sites and distinguished metabolites perturbed by infection between lung tissue and serum samples. Our findings highlight the utility of a spatial approach to understanding the intersection between the lung metabolome, viral infection, and disease severity. Ultimately, this approach will expand our understanding of respiratory disease pathogenesis.

This study investigated the regulatory effects of microRNA-1278 (miR-1278) on airway inflammation, airway reconstruction, and the proliferation and apoptosis of airway smooth muscle cells (ASMCs) induced by transforming growth factor β1 (TGF-β1). The results showed that miR-1278 was upregulated in the blood and lung tissues (LTs) of patients with asthma compared with that in healthy volunteers; miR-1278 expression was also upregulated in asthmatic mice, and miR-1278 inhibition improved the LTs of asthmatic mice. Moreover, miR-1278 inhibited inflammation in asthmatic mice and counteracted the effect of TGF-β1 of induced proliferation and reduced apoptosis in ASMCs. DLRA indicated that miR-1278 targeted the 3′-UTR of Src-homology 2-containing phosphatase 1 (SHP-1). Furthermore, miR-1278 promoted ASMC proliferation, in which TGF-β1 played an important role by regulating the SHP-1/STAT3 signaling pathway. In conclusion, this study showed that miR-1278 played a critical role in the processes of airway remodeling and reduction of apoptosis by targeting SHP-1. [ABSTRACT FROM AUTHOR]