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Workers in the iron casting industries are exposed to various chemicals, especially graphite in furnace process. This study aims to investigate the toxic effects of graphite particles on human lung cells. Particle characteristics were confirmed by electron microscope and light scattering. Cell viability and oxidative stress markers were measured. The expression of oxidative repair genes, namely OGG1, MTH1, and ITPA, was evaluated. The average particle size was determined to be 172.1 ± 11.96 nm. The median inhibition concentration (IC50) of graphite particles was 46.75 µg/mL. Notably, 25 and 50 µg/mL concentrations resulted in significant GSH depletion and MDA production. The high concentration of graphite particles (200 µg/mL) led to OGG1 suppression and increased MTH1 expression. Based on these findings, graphite exposure may induce toxicity in human lung cells by increasing oxidative stress. Further research is necessary to fully understand the mechanisms underlying graphite toxicity. [ABSTRACT FROM AUTHOR]

Context.--Current approaches for characterizing retained lung dust using pathologists' qualitative assessment or scanning electron microscopy with energy-dispersive spectroscopy (SEM/EDS) have limitations. Objective.--To explore polarized light microscopy coupled with image-processing software, termed quantitative microscopy-particulate matter (QM-PM), as a tool to characterize in situ dust in lung tissue of US coal miners with progressive massive fibrosis. Design.--We developed a standardized protocol using microscopy images to characterize the in situ burden of birefringent crystalline silica/silicate particles (mineral density) and carbonaceous particles (pigment fraction). Mineral density and pigment fraction were compared with pathologists' qualitative assessments and SEM/EDS analyses. Particle features were compared between historical (born before 1930) and contemporary coal miners, who likely had different exposures following changes in mining technology. Results.--Lung tissue samples from 85 coal miners (62 historical and 23 contemporary) and 10 healthy controls were analyzed using QM-PM. Mineral density and pigment fraction measurements with QM-PM were comparable to consensus pathologists' scoring and SEM/EDS analyses. Contemporary miners had greater mineral density than historical miners (186 456 versus 63 727/mm³; P = .02) and controls (4542/mm³), consistent with higher amounts of silica/silicate dust. Contemporary and historical miners had similar particle sizes (median area, 1.00 versus 1.14 µm² P = .46) and birefringence under polarized light (median grayscale brightness: 80.9 versus 87.6; P = .29). Conclusions.--QM-PM reliably characterizes in situ silica/silicate and carbonaceous particles in a reproducible, automated, accessible, and time/cost/labor-efficient manner, and shows promise as a tool for understanding occupational lung pathology and targeting exposure controls. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastasis is the stage at which the prognosis substantially decreases for many types of cancer. The ability of cancer cells to disseminate to distant organs, such as the lung, in the body is dependent on the conditioning of these distant sites by the primary tumor. Herein, we investigated the characteristics of the lung, a common site of metastasis, for human breast cancer cell lines that are either metastatic or non-metastatic. The characteristics of the lung were significantly altered by both metastatic and non-metastatic cancer cells, though the non-metastatic cells had distinct effects relative to the metastatic cells. We also investigated the use of a synthetic niche as a surrogate for the lung, which recapitulated the effects of the metastatic and non-metastatic cells. The analysis of the synthetic niche may provide an opportunity to identify disease aggressiveness without the risks associated with the biopsy of vital organs. Metastasis is the stage at which the prognosis substantially decreases for many types of cancer. The ability of tumor cells to metastasize is dependent upon the characteristics of the tumor cells, and the conditioning of distant tissues that support colonization by metastatic cells. In this report, we investigated the systemic alterations in distant tissues caused by multiple human breast cancer cell lines and the impact of these alterations on the tumor cell phenotype. We observed that the niche within the lung, a common metastatic site, was significantly altered by MDA-MB-231, MCF7, and T47 tumors, and that the lung microenvironment stimulated, to differing extents, an epithelial-to-mesenchymal transition (EMT), reducing proliferation, increasing transendothelial migration and senescence, with no significant impact on cell death. We also investigated the ability of an implantable scaffold, which supports the formation of a distant tissue, to serve as a surrogate for the lung to identify systemic alterations. The scaffolds are conditioned by the primary tumor similarly to the lung for each tumor type, evidenced by promoting a pro-EMT profile. Collectively, we demonstrate that metastatic and non-metastatic breast cancers condition distant tissues, with distinct effects on tumor cell responses, and that a surrogate tissue can distinguish the metastatic potential of human breast cancer cell lines in an accessible site that avoids biopsy of a vital organ. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is a genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) that controls chloride current. A number of different CFTR transgenic mouse lines have been developed and subjected to both acute and chronic infection models. However, prior studies showed no substantial differences in bacterial clearance between CF and non-CF mice after single inoculations. Here, using F508del transgenic CF mice, we examined the role of repeated acute Pseudomonas aeruginosa (PA) infection, with the second inoculation 7 days after the first. We found that CF mice were more susceptible to PA infection than non-CF mice following the second inoculation, with non-CF mice showing better neutrophil recruitment and effector functions. We further investigated the characteristics of lung immune cells using single-cell RNA sequencing, finding that non-CF lung neutrophils had more prominent upregulation of adhesion molecules including intercellular adhesion molecule-1 (ICAM-1) compared to CF lung neutrophils. Although people with CF are often colonized with bacteria and have high numbers of neutrophils in the airways during chronic infection, these data suggest that CF neutrophils have deficient effector functions in the setting of repeated acute infection. [ABSTRACT FROM AUTHOR]

Background & Aims: Idiopathic pulmonary fibrosis (IPF) is a devastating chronic form of interstitial lung disease, characterized by an inflammatory infiltrate, deposition of extracellular matrix (ECM) components like collagen, and change in the architectural lung parenchyma. IPF has a poor prognosis and is lethal, with a median survival of 2 to 3 years. The etiology of the disease is obscure; however, several studies indicated that the disease is initiated by inflammation and the release of profibrotic growth factor, namely transforming growth factor β (TGF-β). The definitive treatment for patients has not yet been approved. Although. However, evidence suggests that inflammation plays an essential role in the development and pathogenesis of IPF as a stimulus. However, inflammation is sometimes referred to as a secondary event in fibrosis, partly due to the failure of anti-inflammatory drugs in clinical trials. Therefore, more studies are needed to evaluate the effectiveness of anti-inflammatory therapies. In primary injury or inflammation, TGF-β, a critical cytokine and regulator of fibrosis, promotes inflammation and increases the activity and proliferation of fibroblasts at the site of inflammation, differentiation into myofibroblasts, and production of extracellular matrix, leading to severe pulmonary fibrosis. As a downstream mediator, the connective tissue growth factor (CTGF) is induced by TGF-β and promotes its fibrotic effects, enhancing lung fibrosis through fibroblast proliferation and collagen deposition. Evidence has shown that CTGF expression is increased in fibroblasts of IPF patients. In addition, Endothelin-1 (ET-1) is another downstream mediator of TGF-β fibrogenic responses in fibroblasts, which produces an extracellular matrix and differentiates fibroblasts into myofibroblasts. Also, the expression of tumor necrosis factoralpha (TNF-α), which in addition to its inflammatory properties, also has fibrogenic properties, is significantly increased in the lungs of IPF patients. This expression is associated with increased fibroblasts and the deposition of extracellular matrix proteins in the interstitial region of the lung. In general, these findings indicate that these factors are reasonable targets for designing treatment strategies or evaluating the effect of proposed drugs in the treatment of IPF. Broad-acting anti-inflammatory molecules, including glucocorticoids like Dexamethasone, were considered potential therapy. Glucocorticoids are anti-inflammatory agents that can reduce proinflammatory molecules by suppressing cellular and humoral immunity. Dexamethasone is one of the most potent glucocorticoid drugs; however, despite the various investigations on the inhibition of pulmonary fibrosis, its anti-fibrosis effects are still debated, and there are contradictory findings in this regard. Also, the underlying mechanism of its impact on IPF is not clear. Therefore, in this study, the therapeutic effect of Dexamethasone on pulmonary fibrosis was scrutinized, based on the impact of various players of this scenario, namely the expression of TGF-β, TNF-α, CTGF, ET-1and hydroxyproline. Methods: 6 to 8 week-old male mice were used in this study. All animal care conditions, including temperature, light, and humidity, were observed. Mice aged 8-10 weeks were randomly divided into the following groups, and ten mice were placed in each group. 1. Control group treated with normal saline (Control) 2. Bleomycin inoculated group on day one (BLM) 3. Bleomycin inoculated on day one and dexamethasone-treated for 14 days (BLM+DEXA) The experiments were performed according to the approved guideline from the Faculty Ethics Committee (IR.IUMS.FMD.REC1396.9511127007). Lung fibrosis was induced intratracheal in anesthetized mice using 50 µL bleomycin (5mg/kg) by a single dose. The intervention with Dexamethasone (1mg/Kg/day) was done by 14 days intraperitoneal injection under sterile conditions. The mice were euthanized on day 21 under deep anesthesia, and their lungs were extracted. For evaluation, architectural changes occurred in the lungs based on bleomycin administration and dexamethasone intervention; the left lungs were fixed in formalin. The right lungs were frozen in liquid nitrogen for RNA extraction, gene expression analysis, ELISA, and hydroxyproline assay and were stored at -80 ºC. After 24 hours of immersion in formalin, paraffin blocks were prepared from the left lungs, and tissue incisions were made and transferred to the slide. After paraffin removal and leaching of slides, pathological examinations were performed using Masson Trichrome staining. The amount of hydroxyproline was measured using a hydroxyproline kit. Quantitative measurement of mRNA from CTGF and ET-1 genes in the lungs of mice was performed using real-time PCR. Data analysis of different groups was performed using Prism software and one-way ANOVA and Tukey multiple comparison test. In order to evaluate the anti-fibrotic effect of Dexamethasone in IPF, the bleomycin-induced mouse model was treated with Dexamethasone. After fibrosis was induced by intratracheal BLM administration, histopathological evaluation and hydroxyproline assay, ELISA for measurement of TGF-β and TNF-α, and RT-PCR were performed to evaluate the expression CTGF and ET-1 genes. Results: Histological examination indicated the deposition of collagen after administration of one dose of Bleomycin; an enzymatic analysis of hydroxyproline showed that administration of a single dose of BLM intratracheally leads to extensive fibrosis in the lungs of C57BL/6 mice on day 21. In comparison, 14 days of intraperitoneal treatment with Dexamethasone reduced the severity of fibrosis. Histological examination of Mason trichrome-stained tissue sections from lungs of control mice (receiving saline intratracheally) showed normal lung structure including no extracellular matrix deposition (based on the absence of blue color in the interstitium) and the alveolar space was distinct. While the lung tissue sections of BLM mice showed histopathological changes, including increased fibrotic areas and increased collagen deposition (based on increased blue color), and decreased alveolar spaces compared to the control group. However, lung tissue sections from dexamethasone-treated mice (BLM+DEXA group) showed only mild fibrosis. Dexamethasone treatment reduced the amount of hydroxyproline compared to the Bleomycin treated group; however, this reduction was not statistically significant (P> 0.05). Dexamethasone treatment significantly reduced TGF-β levels in the lungs of the BLM + DEXA group compared with the BLM group (P <0.001). Further, treatment of received Bleomycin (BLM) received mice with Dexamethasone (BLM + DEXA) reduced the amount of TNF-α when compared with Bleomycin received only group nevertheless, this reduction was not statistically significant to mice but statistically significant (P <0.05). The levels of TNF-α and TGF-β in the lungs of Bleomycin treatment mice (BLM) were higher when compared with Normal saline-treated mice (Control) (P <0.001). Dexamethasone treatment can induce its effect by inhibiting a prominent signaling pathway, namely TGF-β. Further, Dexamethasone treatment of Bleomycine received mice significantly reduced the expression of CTGF gene (P <0.001). CTGF expression occurs before the TGF- β cytokine is expressed during the phenomenon of fibrosis. It seems that CTGF is responsible for extracellular accumulation in the fibrosis pathway. In addition, 14 days of treatment of Bleomycin received mice with Dexamethason reduced ET-1 genes in the lungs of the BLM+DEXA group compared with the BLM group (P <0.001). ET1 gene is responsible for the differentiation of fibroblasts to myofibroblasts. It is known that Dexamethasone can ameliorate fibrosis; however, it is not known how this steroid can induce its effect or whether its impact is based on its role in the inhibition of inflammation Conclusion: Our findings showed that intratracheal inoculation of Bleomycin in mice resulted in extensive accumulation of extracellular matrix in the lungs of C57BL/6 mice. Our study demonstrated that administration of Dexamethasone attenuated Bleomycin-induced pulmonary fibrosis in C57BL/6 mice by reducing hydroxyproline, production of two critical cytokines, the TGF-β and TNF-α, also by reduction of CTGF and ET-1 gene expression. Still, further investigations are required to understand how this compound can reduce fibrosis. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Veterinary Research / Revue Canadienne de Recherche Vétérinaire is the property of Canadian Veterinary Medical Association 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.)

Background Intrapulmonary pharmacokinetics may better explain response to tuberculosis (TB) treatment than plasma pharmacokinetics. We explored these relationships by modeling bacillary clearance in sputum in adult patients on first-line treatment in Malawi. Methods Bacillary elimination rates (BER) were estimated using linear mixed-effects modelling of serial time-to-positivity in mycobacterial growth indicator tubes for sputum collected during the intensive phase of treatment (weeks 0–8) for microbiologically confirmed TB. Population pharmacokinetic models used plasma and intrapulmonary drug levels at 8 and 16 weeks. Pharmacokinetic-pharmacodynamic relationships were investigated using individual-level measures of drug exposure (area-under-the-concentration-time-curve [AUC] and C max) for rifampicin, isoniazid, pyrazinamide, and ethambutol, in plasma, epithelial lining fluid, and alveolar cells as covariates in the bacillary elimination models. Results Among 157 participants (58% human immunodeficiency virus [HIV] coinfected), drug exposure in plasma or alveolar cells was not associated with sputum bacillary clearance. Higher peak concentrations (C max) or exposure (AUC) to rifampicin or isoniazid in epithelial lining fluid was associated with more rapid bacillary elimination and shorter time to sputum negativity. More extensive disease on baseline chest radiograph was associated with slower bacillary elimination. Clinical outcome was captured in 133 participants, with 15 (11%) unfavorable outcomes recorded (recurrent TB, failed treatment, or death). No relationship between BER and late clinical outcome was identified. Conclusions Greater intrapulmonary drug exposure to rifampicin or isoniazid in the epithelial lining fluid was associated with more rapid bacillary clearance. Higher doses of rifampicin and isoniazid may result in sustained high intrapulmonary drug exposure, rapid bacillary clearance, shorter treatment duration and better treatment outcomes. [ABSTRACT FROM AUTHOR]

Ethnopharmacological Relevance. Volatile oil is an important bioactive ingredient of Rhodiola tangutica (Maxim.) S.H. Fu, namely, R. tangutica in short. Previous studies have focused on its chemical composition. In our previous research, we found that the bioactive fraction of Rhodiola tangutica could significantly alleviate hypoxia-induced pulmonary hypertension (HPH) in rats. However, it remains unknown whether the volatile oil of Rhodiola tangutica (VORA) could alleviate HPH in rats. Aim of the Study. The main purpose of this study is to explore the effect as well as the corresponding mechanism of VORA among HPH rats, so as to provide evidences for the further exploration of aromatic substances of VORA. Materials and Methods. Seventy-five male Sprague-Dawley (SD) rats were separated into control (Ctr), hypoxia (Hyp), and Hyp+VORA treatment (100 mg/kg/d, 80 mg/kg/d, and 40 mg/kg/d) groups in random. To achieve the chronic hypoxia condition, rats were kept inside the hypobaric chamber with automatically adjusted inner pressure as well as oxygen content equal to those of 4500 m in altitude for 4 continuous weeks. After 4 weeks, the rats' physiological parameters were determined (mean pulmonary artery pressure (mPAP); right ventricular hypertrophy index (RVHI)). Based on hematoxylin and eosin (HE) staining and transmission electron microscope (TEM), morphological features of their lung tissues were also analyzed. Proliferation of pulmonary arterial smooth muscle cells (PASMCs) was detected by MTS Cell Proliferation Colorimetric assay. The levels of glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) in PASMCs were detected through corresponding kits, respectively. The protein levels in PASMCs and HPH rats were evaluated by Western blot (WB). Chemical components of VORA were detected through gas chromatography-mass spectrometer (GC-MS). Results. After induced by hypoxia for 4 weeks, the mPAP and RVHI levels were increased significantly in hypoxia group in contrast to the Ctr group, indicating the establishment of HPH rat model. The subsequent administration of VORA decreased the mPAP and RVHI level. The vascular wall thickness and lumen size were also decreased after treated by VORA compared with Hyp group. Meanwhile, VORA suppressed the proliferation and oxidant stress in PASMCs. Therefore, the effect of VORA on decreasing vascular wall thickening and lumen size could be related to its antiproliferation effect on PASMCs. In addition, compared to the Hyp group, VORA downregulated the ACE, AngII, and AT1R protein expressions but increased ACE2 and MAS protein expressions (P < 0.05). A total of 48 constituents in VORA were identified by GC-MS in comparison with reference standards as well as the reference pieces of literatures. Conclusions. HPH rat model as established based on the significant increased mPAP and RVHI. VORA presented a significant antihypoxia function plus an inhibiting effect on PASMC proliferation induced by hypoxia. Moreover, VORA treatment inhibited oxidative stress among PASMCs. With regard to the mechanism, VORA reduced ACE, AngII, and AT1R protein expressions but increased ACE2 and MAS protein expressions. There were 48 constituents in VORA identified by GC-MS. [ABSTRACT FROM AUTHOR]

Purpose: Exercise-induced arterial hypoxemia (EIAH) has been reported in patients with juvenile thyroid cancer treated with radioiodine for lung metastases. This retrospective study tested the hypothesis that EIAH is due to ventilation-perfusion-mismatch in this rare pulmonary condition. Methods: 50 patients (age 13-23 years) treated for juvenile thyroid carcinoma and lung metastasis with 131I and 24 controls with thyroid cancer but without lung metastases and prior 131I-treatment were assessed in a state of acute hypothyroidism by computed tomography of the lungs, pulmonary function testing, cardiopulmonary exercise test with measurements of gas exchange, oxygen saturation, alveolar-arterial difference in pO2 (p(A-a)O2) and pCO2 (p(ET-a)CO2). Results: 10 of the 50 patients with lung metastases showed EIAH. They had more pronounced pulmonary fibrosis on computed tomography, a widened p(A-a)O2, and p(ET-a)CO2, a lower DVE/DVCO2-slope, a lower respiratory rate and no increased dead space ventilation. A more pronounced EIAH was associated with male gender, younger age, lower diffusion capacity, higher p(ET-a)CO2 during exercise and a higher peak exercise tidal volume over vital capacity ratio. Conclusion: EIAH in patients with thyroid carcinoma and pulmonary metastases is not related to ventilation-perfusion mismatch but to alveolar hypoventilation, possibly related to an increased work of breathing with pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Background Children and older adults with coronavirus disease 2019 (COVID-19) display a distinct spectrum of disease severity yet the risk factors aren't well understood. We sought to examine the expression pattern of angiotensin-converting enzyme 2 (ACE2), the cell-entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the role of lung progenitor cells in children and older patients. Methods We retrospectively analyzed clinical features in a cohort of 299 patients with COVID-19. The expression and distribution of ACE2 and lung progenitor cells were systematically examined using a combination of public single-cell RNA-seq data sets, lung biopsies, and ex vivo infection of lung tissues with SARS-CoV-2 pseudovirus in children and older adults. We also followed up patients who had recovered from COVID-19. Results Compared with children, older patients (>50 years.) were more likely to develop into serious pneumonia with reduced lymphocytes and aberrant inflammatory response (P =.001). The expression level of ACE2 and lung progenitor cell markers were generally decreased in older patients. Notably, ACE2 positive cells were mainly distributed in the alveolar region, including SFTPC positive cells, but rarely in airway regions in the older adults (P <.01). The follow-up of discharged patients revealed a prolonged recovery from pneumonia in the older (P <.025). Conclusions Compared to children, ACE2 positive cells are generally decreased in older adults and mainly presented in the lower pulmonary tract. The lung progenitor cells are also decreased. These risk factors may impact disease severity and recovery from pneumonia caused by SARS-Cov-2 infection in older patients. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic obstructive pulmonary disease [COPD] is a very common disease in developing as well as in developed countries. Using CT has a growing interest to give a phenotypic classification helping the clinical characterization of COPD patients. So, the aim of the present study was to evaluate whether there was a significant correlation between quantitative computed tomography lung analysis and pulmonary function tests in chronic obstructive pulmonary disease patients. Results The study included 50 male patients with a mean age of 62.82 years ± 8.65 years standard deviation [SD]. Significant correlation was found between the pulmonary function tests [FEV1 and FEV1/FVC ratio], and all parameters of quantitative assessment with – 950 HU [the percentage of low-attenuation areas (% LAA)]. Pulmonary function tests according to GOLD [Global Initiative for Chronic Obstructive Lung Disease] guidelines revealed that 4% had normal pulmonary function, 8% had mild obstructive defect, 32% had moderate obstructive defect, 26% had severe obstructive defect, and 30% had very severe obstructive defect. Conclusion Automated CT densitometry defining the emphysema severity was significantly correlated with the parameters of pulmonary function tests and providing an alternative, quick, simple, non-invasive study for evaluation of emphysema severity. Its main importance was the determination of the extent and distribution of affected emphysematous parts of the lungs especially for selecting the patients suitable for the lung volume reduction surgery.

INTRODUCTION: There are several factors predicting evolution in carcinoid tumors (CT) to date including the Ki67 role. AIMS: The aim of this study is to identify a KI67 cut-off point for a population of CT and determine its prognostic implication in global and disease-free survival. METHODS: Hematoxylin-eosin slides of 102 CT were revised. The percentage of cells expressing Ki 67 was determined manually. STATISTICAL ANALYSIS: The variables were compared with the t-test or the Wilcoxon test according to their distribution, the categorical ones with Chi-square or Fisher's test. The best cut-off point was established by constructing receiver operating characteristic curves, then using that value as a dichotomous variable. RESULTS: 72 typical carcinoids (TC) and 30 atypical carcinoids (AC) were analyzed; 66% were female. Median age (TC 38 vs. AC 51, P = 0.001), Ki67 expression (TC 0.63 vs. AC 2, P = 0.003), tumor size (TC 2.5 vs. AC 2.6, P = 0.001), the percentage relapse (TC 3.4% vs. AC 23%, P = 0.006), and the number of deaths (TC 1 vs. AC 4, P = 0.042) were significantly higher in the AC subgroup. The best cut-off point for Ki 67 was 0.755 (area under the curve AUC 0.564, 95% confidence interval 0.270–0.857), with no significant differences found in the disease-free and overall survival curves when considering values < or ≥ at the established cut-off point. The best cut-off point of the Ki-67 when exclusively analyzing AC was 1.18. When using this value as a predictive variable, a marginal statistical association was observed between Ki-67 expression, mortality (P = 0.077), and the frequency of relapses (P = 0.054). CONCLUSIONS: Histological type is the best predictor of prognosis in the carcinoid tumor group. In the AC subgroup, the marginal association between mortality, frequency of relapses and Ki values 67 ≥ 1.18 has clinical relevance future analyses are required to determine the real predictive value of this variable. [ABSTRACT FROM AUTHOR]

BACKGROUND: Traffic-related air pollution (TRAP) is made up of complex mixtures of particulate matter, gases and volatile compounds. However, the effects of TRAP on the cardiopulmonary system in most animal studies have been tested using acute exposure to singular pollutants. The cardiopulmonary effects and molecular mechanisms in animals that are chronically exposed to unmodified air pollution as a whole have yet to be studied. Additionally, sex-dependent toxicity of TRAP exposure has rarely been evaluated. OBJECTIVES: This study sought to assess the cardiopulmonary effect of chronic exposure to unmodified, real-world TRAP in both female and male rats. METHODS: Four-week-old male and female rats were exposed to TRAP or filtered air for 14 months in a novel facility drawing air from a major freeway tunnel system in Northern California. Inflammation and oxidative stress markers were examined in the lung, heart, spleen, and plasma, and TRAP deposits were quantified in the lungs of both male and female rats. RESULTS: Elemental analysis showed higher levels of eight elements in the female lungs and one element in the male lungs. Expression of genes related to fibrosis, aging, oxidative stress, and inflammation were higher in the rat hearts exposed to TRAP, with female rats being more susceptible than males. Enhanced collagen accumulation was found only in the TRAP-exposed female hearts. Plasma cytokine secretion was higher in both female and male rats, but inflammatory macrophages were higher only in TRAP-exposed male spleens. DISCUSSION: Our results in rats suggest pathological consequences from chronic TRAP exposure, including sex differences indicating females may be more susceptible to TRAP-induced cardiac fibrosis. [ABSTRACT FROM AUTHOR]

Statistical shape analysis of lung is a reliable alternative method for diagnosing pulmonary diseases such as tuberculosis (TB). The 2D contour-based lung shape analysis is investigated and developed using Fourier descriptors (FDs). The proposed 2D lung shape analysis is carried out in threefold: (1) represent the normal and the abnormal (i.e. pulmonary tuberculosis (PTB)) lung shape models using Fourier descriptors modeling (FDM) framework from chest X-ray (CXR) images, (2) estimate and compare the 2D inter-patient lung shape variations for the normal and abnormal lungs by applying principal component analysis (PCA) techniques, and (3) describe the optimal type of contour-based feature vectors to train a classifier in order to detect TB using one publicly available dataset-namely the Montgomery dataset. Since almost all of the previous works in lung shape analysis are content-based analysis, we proposed contour-based lung shape analysis for statistical modeling and feature description of PTB cases. The results show that the proposed approach is able to explain more than 95% of total variations in both of the normal and PTB cases using only 6 and 7 principal component modes for the right and the left lungs, respectively. In case of PTB detection, using 138 lung cases (80 normal and 58 PTB cases), we achieved the accuracy (ACC) and the area under the curve (AUC) of 82.03% and 88.75%, respectively. In comparison with existing state-of-art studies in the same dataset, the proposed approach is a very promising supplement for diagnosis of PTB disease. The method is robust and valuable for application in 2D automatic segmentation, classification, and atlas registration. Moreover, the approach could be used for any kind of pulmonary diseases. Graphical abstract Contour-based lung shape analysis in order to detect tuberculosis: modeling and feature description. [ABSTRACT FROM AUTHOR]

Objective. The study aimed to explore the effect of total flavonoids of Oxytropis falcata Bunge (FOFB) on the expression of p-JAK1/p-STAT1 and SOCS3 proteins in idiopathic pulmonary fibrosis (IPF). Methods. Rats model with IPF was established by one-off intratracheal injection of bleomycin (BLM, 5 mg/kg). After 14 days, the same volume of low dose (100 mg/kg), medium dose (200 mg/kg), and high dose (400 mg/kg) of FOFB and prednisolone acetate (20 mg/kg) as positive control drugs, as well as normal saline, were orally administered to rats once a day for 28 consecutive days. Subsequently, the degree of fibrosis and alveolitis in rat lung tissue was observed, respectively, by HE and Masson staining. Further more, observing the ultrastructure of lung tissue by transmission electron microscopy (TEM), the detection of JAK/STAT pathway related indicators including p-JAK1, p-STAT1, and SOCS3 with immunohistochemistry and SOCS3 with real-time PCR (RT-PCR) was performed. Results. Compared with the BLM group, the degree of alveolitis and fibrosis improved significantly, and the expression of p-JAK1 and p-STAT1 decreased; conversely, the expression of SOCS3 increased in the treatment group. Conclusion. IPF causes high expression of p-JAK1 and p-STAT1 and low expression of SOCS3. FOFB can play a role in the treatment of IPF via upregulating SOCS3 and downregulating p-JAK1 and p-STAT1. [ABSTRACT FROM AUTHOR]

Background: Pulmonary dysfunction is one of the critical complications of a stroke. However, it remains unclear whether the mechanism is caused by either neurogenic or inflammatory reactions. The present study aimed to determine the effect of cerebral ischemia-reperfusion injury and the role of the vagus nerve on hypoxic pulmonary vasoconstriction (HPV) in rats. Methods: This study was performed at Shiraz University of Medical Sciences, Shiraz, Iran, 2018. Male Sprague Dawley rats (n=56) were divided into four groups, namely the sham, vagotomy (Vag), 1 hour of ischemia followed by 23 hours of reperfusion without vagotomy (I/R) and with vagotomy (I/R+Vag). Neurological deficit scores and total infarct volumes of brains were measured in the I/R and I/R+Vag groups. Pulmonary artery pressure and lung weight were continuously registered during ventilation with normoxic and hypoxic gases in the isolated lungs. The blood gas parameters and the lung malondialdehyde (MDA) level of each group were also evaluated. ANOVA, with Tukey's post hoc test and t test, was used to compare the variables in the experimental groups. Results: The infarct volume of the brains in the I/R and I/R+Vag groups were similar. HPV in the I/R group was lower than those in the sham and Vag groups, while vagotomy reversed this response in the I/R+Vag group (P=0.004). In the I/R group, PO2 and pH were lower, and PCO2 was higher than those in the sham and Vag groups. The lung MDA level in the I/R group was higher than that in the Vag group (P=0.019). Conclusion: Brain ischemia-reperfusion injury decreased HPV independent of increased MDA in the lung, whereas vagotomy improved HPV by repairing the blood-gas barrier and oxygen sensing. [ABSTRACT FROM AUTHOR]

B7-H3 has emerged as a promising target for cancer immunotherapy. We assessed the role of B7-H3 expression in tumour-infiltrating immune cells in non–small-cell lung cancer (NSCLC). Tumour-infiltrating immune cell characterisation was performed by flow cytometry in a prospective cohort, whereas the relationship between B7-H3 expression and clinicopathological features was explored in a retrospective cohort. B7-H3 expression was detected in tumour/epithelial cells and immune cells, including macrophages, monocytes, dendritic cells (DCs) and myeloid-derived suppressor cells. B7-H3 was expressed at higher levels in cells within the tumour than in cells within non-neoplastic tissues. B7-H3 expression score in tumour cells positively correlated with the amount of CD45+ immune cells (rho = 0.305, P = 0.010), CD8+ T-cells (rho = 0.330, P = 0.005), and the percentage of CD8+/CD3+ T-cells (rho = 0.403, P < 0.001). Patients with high tumoural B7-H3 expression showed increased numbers of immune cells (P = 0.002), CD8+ T-cells (P = 0.011), natural killer cells (P = 0.073) and plasmacytoid DCs (P = 0.015). Tumoural B7-H3 expression was higher in males, smokers, squamous cell carcinomas, tumours with wild-type EGFR , poor differentiation, larger size and nodal metastasis (P < 0.05, all). Tumoural B7-H3 expression was associated with PD-L1 expression (P = 0.001), shorter 5-year overall survival (P = 0.012) and poor survival after anti–PD-1 blockade (P = 0.026). Tumoural B7-H3 overexpression was associated with increased tumour-infiltrating cytotoxic lymphocytes and poor prognosis in NSCLC. Thus, B7-H3 is a promising prognostic biomarker and immunotherapeutic target in NSCLC. • B7-H3–related tumour immune microenvironment was comprehensively analysed in non–small-cell lung cancer (NSCLC). • B7-H3 expression is higher in cells within tumour than those within non-neoplastic tissue. • NSCLC with B7-H3 overexpression was highly infiltrated by cytotoxic lymphoid cells and antigen presenting cells. • B7-H3 overexpression was associated with adverse clinicopathological feature in NSCLC. • B7-H3 overexpression was associated with poor prognosis in patients with resected NSCLC or in those received PD-1 blockade. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Trauma & Emergency Surgery / Ulusal Travma ve Acil Cerrahi Dergisi is the property of KARE Publishing 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.)

Background: The acute respiratory distress syndrome (ARDS) and cardiogenic pulmonary edema (CPE) are both characterized by an increase in lung edema that can be measured by computed tomography (CT). The aim of this study was to compare possible differences between patients with ARDS and CPE in the morphologic pattern, the aeration, and the amount and distribution of edema within the lung. Methods: Lung CT was performed at a mean positive end-expiratory pressure level of 5 cm H2O in both groups. The morphological evaluation was performed by two radiologists, while the quantitative evaluation was performed by a dedicated software. Results: A total of 60 patients with ARDS (20 mild, 20 moderate, 20 severe) and 20 patients with CPE were enrolled. The ground-glass attenuation regions were similarly present among the groups, 8 (40%), 8 (40%), 14 (70%), and 10 (50%), while the airspace consolidations were significantly more present in ARDS. The lung gas volume was significantly lower in severe ARDS compared to CPE (830 [462] vs 1120 [832] mL). Moving from the nondependent to the dependent lung regions, the not inflated lung tissue significantly increased, while the well inflated tissue decreased (ρ = 0.96-1.00, P <.0001). Significant differences were found between ARDS and CPE mostly in dependent regions. In severe ARDS, the estimated edema was significantly higher, compared to CPE (757 [740] vs 532 [637] g). Conclusions: Both ARDS and CPE are characterized by a similar presence of ground-glass attenuation and different airspace consolidation regions. Acute respiratory distress syndrome has a higher amount of not inflated tissue and lower amount of well inflated tissue. However, the overall regional distribution is similar within the lung. [ABSTRACT FROM AUTHOR]

The article presents a study discussing metabolic adaptation of airway smooth muscle cells to a SPHK2 substrate precedes cytostasis. Topics discussed include use of Sigma-Aldrich colorimetric BrdU cell proliferation assay was used to quantify DNA synthesis; ways to quantify SPHK2 immunoreactivity; and assessment of mitochondrial content.

The article presents a study discussing how airway surface liquid (ASL) has innate antiviral activity that is reduced in cystic fibrosis. Topics discussed include materials and methods used for viruses and tissue culture; ways to measure antiviral activity in porcine serum from newborn pigs; and effects of pH on the antiviral properties of ASL and antimicrobial proteins/peptides.

The article presents study related to embedding of precision-cut lung slices (PCLS) in engineered hydrogel biomaterials supports extended ex vivo culture. Topics discussed include materials and methods used to prepare PCLS; characterization of mechanical properties of elastic modulus (E) of murine lung tissue samples; and immunostaining, fluorescence microscopy, and image analysis.

Background: Several studies suggested the association between tobacco and cannabis smoking and the risk of primary spontaneous pneumothorax (PSP), but none demonstrated cannabinoids in human lung tissues. Objectives: The aim of this study was to identify cannabinoids in lung specimens of young cannabis smokers, operated for PSP, and investigate on their pathologic findings, to determine the role of cannabis in PSP pathogenesis. Method: A prospective, multicenter study was conducted, enrolling patients admitted for PSP. Inclusion criteria were PSP requiring surgical treatment and history of cannabis smoking, associated or not to tobacco. Control cases were nonsmokers, and tobacco only smokers operated for PSP. Lung apex wedge resection by video-assisted thoracic surgery was performed. Two lung specimens, for pathological and toxicological examination, were taken from each patient. Results: Twenty-nine male patients were enrolled: 21 (72.4%) tobacco and cannabis smokers, 2 (7%) cannabis only smokers, 3 (10.3%) tobacco only smokers, 3 (10.3%) nonsmokers; all underwent lung apicectomy, 4 bilateral surgery, for a total of 33 procedures. Typical PSP pathologic findings were mainly detected in control cases, other alterations in cannabis users. Lung specimens resulted positive for cannabinoids on 22/33 cases (19/22 reported being, 3/22 not being cannabis smokers), negative on 11/33 (3/11 reported not being, 7/11 having been cannabis smokers, 1/11 cannabis smoker). Conclusions: Our study demonstrated the presence of cannabinoids and particular pathologic alterations in lung tissues of young cannabis smokers with PSP, supporting the correlation between this disease and marijuana abuse and suggesting spontaneous pneumothorax "secondary to marijuana" as a new nosological entity. [ABSTRACT FROM AUTHOR]

Abstract Introduction Computed tomography (CT) lung analysis is a new CT technique that allows assessment of emphysema in a quantitative pattern to avoid subjective analysis. Objective The aim of this study was to assess the role of a new CT lung analysis in quantitative assessment of pulmonary emphysema. Patients and methods Totally, 30 patients with emphysema were included in this study who presented to the Chest Department of Ain Shams University for follow-up. All patients underwent full history taking, clinical examination, spirometry, and body plethysmography, and were then referred to the Radiology Department for noncontrast chest CT followed by lung volume analysis. Four patients among them were followed-up before and after medical volume reduction therapy. Results There was a direct relationship between the CT lung volume, the percentage of low-attenuation area, as well as the total lung capacity measured by body plethysmography. Totally, 12 cases were found to be grade I by the Goddard score, with nine of them found to be GOLD I and three of them found to be GOLD II. Fifteen cases were found to be grade II by the Goddard score, with 12 of them found to be GOLD II and three of them found to be GOLD III/IV. Three cases were found to be grade III by the Goddard score with all of them found to be GOLD III/IV. The main site for distribution of the clusters according to their number was in the left upper lobe, whereas according to the cluster volume the main site was the right upper lobe. CT lung analysis guided the site of injection in four patients who underwent volume reduction therapy. Conclusion CT lung analysis is a new technique that allows quantitative assessment of emphysema, which is important for categorization, follow-up, and treatment strategies. It must be added as a routine study accompanied by spirometric function.

Background Children with cystic fibrosis (CF) can develop life-threatening infections of Mycobacterium abscessus. These present a significant clinical challenge, particularly when the strains involved are resistant to antibiotics. Recent evidence of within-patient subclones of M. abscessus in adults with CF suggests the possibility that within-patient diversity may be relevant for the treatment of pediatric CF patients. Methods We performed whole-genome sequencing (WGS) on 32 isolates of M. abscessus that were taken from multiple body sites of 2 patients with CF who were undergoing treatment at Great Ormond Street Hospital, United Kingdom, in 2015. Results We found evidence of extensive diversity within patients over time. A clustering analysis of single nucleotide variants revealed that each patient harbored multiple subpopulations, which were differentially abundant between sputum, lung samples, chest wounds, and pleural fluid. The sputum isolates did not reflect the overall within-patient diversity and did not allow for the detection of subclones with mutations previously associated with macrolide resistance (rrl 2058/2059). Some variants were present at intermediate frequencies before the lung transplants. The time of the transplants coincided with extensive variation, suggesting that this event is particularly disruptive for the microbial community, but the transplants did not clear the M. abscessus infections and both patients died as a result of these infections. Conclusions Isolates of M. abscessus from sputum do not always reflect the entire diversity present within the patient, which can include subclones with differing antimicrobial resistance profiles. An awareness of this phenotypic variability, with the sampling of multiple body sites in conjunction with WGS, may be necessary to ensure the best treatment for this vulnerable patient group. [ABSTRACT FROM AUTHOR]

Raman spectroscopy is non-destructive method that allows monitoring of biological tissues with minimal intervention. FT-Raman (λ ex 1064 nm) and NIR-Vis-Raman (λ ex 785 nm) spectroscopic measurements were used in ex vivo analysis of normal, non-cancerous abnormal and cancerous lung tissues. Spectroscopic discrimination of the lung tissue samples was made by the use of the ratio of characteristic bands and multivariate statistical methods (PCA, LDA). The combination of Raman spectroscopy and multivariate statistics may have a diagnostic potential for recognizing of cancer lesions in lung. Unlabelled Image • Raman spectroscopy allows monitoring of biological tissues with minimal intervention. • Raman measurements at λ ex 1064 nm and 785 nm were used in ex vivo analysis of lung tissues. • Normal, non-cancerous abnormal and cancerous samples were discriminated by statistical evaluation of the spectra. • Raman spectroscopy may have a diagnostic potential for recognizing of cancer lesions in lung. [ABSTRACT FROM AUTHOR]

Background: This study aimed to analyze cause-specific mortality in lung cancer patients over 80 years old undergoing surgery. Methods: This retrospective, multi-institutional analysis included patients aged ≥ 80 years who underwent radical surgery for primary lung cancer from January 1998 to December 2015. Preoperative clinical data, surgical results, survival, and cause of death were evaluated. Competing risk analysis for cause-specific mortality was performed. Results: Of the 337 patients (median age 82 years) enrolled and analyzed, 68.1% were male. There were 52 and 44 cancer-specific and non-cancer-specific deaths, respectively. On competing risk regression analysis, non-cancer-specific deaths were significantly associated with male sex (hazard ratio [HR]: 3.06, 95% confidence interval [CI]: 1.02–9.12, p = 0.046), coronary artery disease (HR: 2.49, 95% CI: 2.49 [1.14–5.47], p = 0.02), interstitial pneumonia (HR: 3.58, 95% CI: 1.73–7.40, p < 0.001), and pathological stage III (HR: 3.83, 95% CI: 1.44–10.13, p = 0.007). In contrast, cancer-specific deaths were significantly associated with limited resection (HR: 1.99, 95% CI: 1.02–3.89, p = 0.04) and pathological stage III (HR: 3.13, 95% CI: 1.44–6.80, p = 0.004). The 5-year cumulative incidences of lung cancer-specific and non-cancer-specific deaths were 18.0% and 15.9%, respectively. Conclusions: Prognostic factors for non-cancer-specific death were different from those of cancer-specific death, except for pathological stage. Each prognostic factor should be considered when deciding surgical indication and procedure and monitoring for pulmonary events during outpatient follow-up. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI), a persistent lung inflammatory response syndrome, may evolve into acute respiratory distress syndrome (ARDS). Characterized by rapid onset, critical features, and a complex etiology, ALI remains a challenging critical respiratory disease. Recently, mesenchymal stem cells (MSCs) have provided a new solution for the treatment of ALI. We built a lipopolysaccharide (LPS)-induced ALI model in mice. After treatment with human umbilical cord mesenchymal stem cells (hUC-MSCs), FTY720, or a combination of hUC-MSCs and FTY207, the lung inflammatory response was apparently attenuated. To understand the mechanism underlying MSCs treatment of ALI at the genetic level, significant differentially expressed long non-coding RNAs (lncRNAs) between the treatment and model groups were analyzed using microarray technology. Moreover, genetic gene prediction, gene ontology (GO) analysis, pathway analysis, and transcription factor (TF) prediction were carried out. The results showed that a total of 66 lncRNAs were differentially expressed in all three treatment groups, including 8 up-regulated and 58 down-regulated lncRNAs. LncRNA A_30_P01029806 and A_30_P01029194, which were down-regulated, were involved in the signaling pathways closely related to ALI. Through further TF analysis, we identified several significant TFs which lay a foundation for revealing the mechanism underlying lncRNAs treatment of ALI. LncRNA A_30_P01029806 and A_30_P01029194 may serve as candidate biomarkers in the diagnosis and treatment of ALI. • 66 lncRNAs were differentially expressed in all three treatment groups. • Two lncRNAs were involved in the signaling pathways closely related to ALI. • Several significant TFs related to the two lncRNAs were identified through TF prediction. • The two lncRNAs may serve as candidate biomarkers in the diagnosis and treatment of ALI. [ABSTRACT FROM AUTHOR]

Background and Objective: Lung adenocarcinoma (LUAD) is the most common histological type of all lung cancers and is associated with genetic and epigenetic aberrations. The tumor, node, and metastasis (TNM) stage is the most authoritative indicator of the clinical outcome in LUAD patients in current clinical practice. In this study, we attempted to identify novel genetic and epigenetic modifications and integrate them as a predictor of the prognosis for LUAD, to supplement the TNM stage with additional information. Methods: A dataset of 445 patients with LUAD was obtained from The Cancer Genome Atlas database. Both genetic and epigenetic aberrations were screened for their prognostic impact on overall survival (OS). A prognostic score (PS) integrating all the candidate prognostic factors was then developed and its prognostic value validated. Results: A total of two micro-RNAs, two mRNAs and two DNA methylation sites were identified as prognostic factors associated with OS. The low- and high-risk patient groups, divided by their PS level, showed significantly different OS (p < 0.001) and recurrence-free survival (RFS; p = 0.005). Patients in the early stages (stages I/II) and advanced stages (stages III/IV) of LUAD could be further subdivided by PS into four subgroups. PS remained efficient in stratifying patients into different OS (p < 0.001) and RFS (p = 0.005) when the low- and high-risk subgroups were in the early stages of the disease. However, there was only a significant difference in OS (p = 0.04) but not RFS (p = 0.2), between the low-risk and high-risk subgroups when both were in advanced stages. Conclusion: PS, in combination with the TNM stage, provides additional precision in stratifying patients with significantly different OS and RFS prognoses. Further studies are warranted to assess the efficiency of PS and to explain the effects of the genetic and epigenetic aberrations observed in LUAD. [ABSTRACT FROM AUTHOR]

Background: Growing evidence indicates that high phosphoserine phosphatase (PSPH) expression is associated with tumor prognosis in many types of cancers. However, the role of PSPH in non‐small cell lung cancer (NSCLC) is unclear. The purpose of this study was to investigate the clinical significance of PSPH in NSCLC. Methods: One hundred forty‐three patients with histologically confirmed NSCLC who underwent surgery were included. Quantitative real‐time PCR and Western blot were used to assess PSPH expression in paired tumor and corresponding adjacent non‐tumorous tissues. The role of PSPH in invasion and cell growth was investigated in vitro. Results: Compared to adjacent normal lung tissues, PSPH messenger RNA and protein levels were significantly higher in NSCLC tissues, and the PSPH expression level was positively related to clinical stage, metastasis, and recurrence. High PSPH expression was predictive of poor overall survival. A549 cells transfected with small interfering‐PSPH showed inhibited cell migration, invasion, and proliferation. We further demonstrated that PSPH might promote the invasive capabilities of NSCLC cells through the AKT/AMPK signaling pathway. Conclusion: Our results indicate that PSPH may act as a putative oncogene in NSCLC, and may be a vital molecular marker for the metastasis and proliferation of NSCLC cells by regulating the AKT/AMPK signaling pathway. [ABSTRACT FROM AUTHOR]

• dp -BREATH provides well-segmented lung regions by classifying superpixels in CT scans. • dp -BREATH models pathological lung patterns as a Gaussian Mixing Model. • dp -Breath gives the probability of a region to contain each pathology being analyzed. • dp -BREATH highlights abnormal superpixel regions within the CT scan using heat maps. • Highlighted regions provide probabilities information regarding abnormal findings. Background and Objective: Identifying abnormalities in chest CT scans is an important and challenging task, demanding time and effort from specialists. Different parts of a single lung image may present both normal and abnormal characteristics. Thus, detecting a single lung as healthy (normal) or not is inaccurate. Methods: In this work we propose dp- BREATH, a method capable of detecting abnormalities in pulmonary tissue regions and directing the specialist's attention to the lung region containing them. It starts by highlighting regions that may indicate pulmonary abnormalities based on the healthy pulmonary tissue behavior using a superpixel-based approach and a heat map visualization. This is achieved by modeling regions of healthy tissue using a statistical model. All regions considered abnormal are modeled and classified according to their probability of containing each of the studied abnormalities. Further, dp- BREATH provides a better recognition of radiological patterns, with the likelihood of a selected lung region to contain abnormalities. Results: We validate the statistical model of healthy and abnormal detection using a representative dataset of chest CT scans. The model has shown almost no overlap between healthy and abnormal regions, and the detection of abnormalities presented precision higher than 86%, for all recall values. Additionally, the fitted models describing pulmonary radiological patterns present precision of up to 87%, with a high separation for three of five radiological patterns. Conclusions: dp- BREATH's heat map representation and its list of radiological patterns probabilities provided are intuitive methods to assist physicians during diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: To determine the histopathological pattern of lung cancers in Madinah, Saudi Arabia. Methods: This retrospective histopathology-based study was conducted at the Department of Pathology, King Fahad Hospital, Madinah, Saudi Arabia and comprised cases of lung cancers for 11 years between January 2006 and December 2017. The data was obtained from histopathologic reports and evaluated for age, gender, site of tumor, and histopathological patterns with grade. Results: A total of 138 patients with lung cancers were identified, 103 (74.6%) patients were males and 35 (25.4%) patients were females with a male to female ratio of 2.9:1. The ages ranged from 6 to 97 years with a mean age of 60.6 ± 14.7 years. Adenocarcinoma (AC) was the most common pathological type (47.8%), followed by squamous cell carcinoma (SCC) (25.3%), neuroendocrine tumor (8.7%) and metastatic carcinoma (8%). Both ACs and SCCs showed a male predominance with a ratio of 2.9:1 (male) and 4.8:1 (female). The majority of ACs (56.5%) and SCCs (65.7%) were moderately differentiated. Conclusion: The study established a baseline of lung cancer pattern on the basis of histopathological experience in a tertiary referral hospital in Al-Madinah Al-Munawwarah, Saudi Arabia. The results obtained showed similarities with that in the world literature and Saudi national studies. [ABSTRACT FROM AUTHOR]

• CDC25C has prognostic value in lung adenocarcinoma based on data from the cancer genome atlas. • High CDC25C levels were associated with an advanced stage, lymph node invasion, distant metastasis, and poor status. • High CDC25C expression was associated with poor overall survival and progression-free survival. • CDC25C may be involved in LUAD via the regulation of the cell cycle and FAS -mediated apoptosis. Cell division cycle 25C (CDC25C) is involved in the regulation of the G2/M phase transition and is associated with various cancers, including non-small cell lung cancer. We evaluated its prognostic value in lung adenocarcinoma (LUAD) based on data from The Cancer Genome Atlas (TCGA). Kruskal–Wallis test, Wilcoxon signed-rank test, and logistic regression were used to evaluate relationships between clinical-pathologic features and CDC25C expression. Cox regression analyses and the Kaplan–Meier method were used to evaluate factors contributing to prognosis. Gene set enrichment analysis (GSEA) was performed. High CDC25C expression in LUAD was associated with a high tumor extent (odds ratio (OR) = 2.23 (1.52–3.29), P < 0.001), regional lymph node invasion (OR = 2.18 (1.48–3.22), P < 0.001), OR = advanced stage (OR = 2.47 (1.72–3.59), P < 0.001), and poor status (OR = 1.87 (1.19–2.96), P = 0.007). A univariate analysis showed that high CDC25C expression is associated with a short overall survival (OS) (HR: 1.873; 95% CI: 1.385–2.535; P < 0.001) and poor progression-free survival (HR: 1.503; 95% CI: 1.173–1.926; P = 0.0012). In a multivariate analysis, high CDC25C expression was associated with poor OS (HR = 2.193; CI: 1.394–3.452, P = 0.001). GSEA showed the enrichment of cell cycle, apoptosis, p53-dependent G1 DNA damage response, S-phase, mitotic M-M G1 phases, and FA-mediated cell death in the CDC25C high-expression phenotype. CDC25C predicts poor prognosis in LUAD and may function in cell cycle regulation and FAS-mediated apoptosis. [ABSTRACT FROM AUTHOR]

Background During pregnancy, the Zika virus (ZIKV) replicates in the placenta and central nervous system (CNS) of infected fetuses; nevertheless, the ability of ZIKV to replicate in other fetal tissues has not been extensively characterized. Methods We researched whether dissemination of congenitally-acquired ZIKV outside the CNS exists by searching for the accumulation of the viral envelope protein, ZIKV ribonucleic acid (RNA), and infectious viral particles in different organs of a deceased newborn with Congenital Zika Syndrome. A real-time qualitative polymerase chain reaction (qPCR) was used to detect ZIKV RNA in the brain, thymus, lungs, kidneys, adrenal glands, spleen, liver, and small intestine. The same tissues were analyzed by indirect immunofluorescence and immunoperoxidase assays using the monoclonal antibody 4G2 to detect ZIKV envelope antigens. Isolation of infectious ZIKV in a cell culture was carried out using brain and kidney samples. Results A postmortem, virological analysis of multiple organs, such as the kidneys (epithelial cells in the renal tubules), lungs (bronchial epithelia), thymus (epithelial cells inside the Hassall's corpuscles), and brain (neurons, ependymal cells, and macrophages) revealed the presence of ZIKV RNA and envelope antigens. Other tissues of the deceased newborn tested positive by qPCR for Epstein-Barr virus and human herpesvirus 6, including the brain cortex (Epstein-Barr) and the thymus, kidneys, and adrenal glands (human herpesvirus 6). The kidneys were identified as a significant niche for viral replication, given that infectious particles were successfully isolated from renal tissues. Conclusions Our findings demonstrate the ability of congenitally-acquired ZIKV to produce disseminated infections and the viral tropism towards epithelial cells. [ABSTRACT FROM AUTHOR]

The aim of this paper is to identify key genes in lung adenocarcinoma (LUAD) through weighted gene co-expression network analysis (WGCNA), and to further understand the molecular mechanism of LUAD. 107 gene expression profiles were downloaded from GSE10072 in the GEO database. We performed rigorous processing of the initial gene expression profile data. Subsequently, we used WGCNA to identify disease-driven modules and enforced functional enrichment analysis. The key genes were defined as the most connected genes in the driver module and were validated using the GSE75037 and TCGA database. GSE10072 removed 41 unpaired lung samples and 4 outliers. By analyzing the 62 samples using WGCNA, we obtained 26 modules and identified the brown and magenta modules as the driving modules for the LUAD. We found that the "Cell cycle", "Oocyte meiosis" and "Progesterone-mediated oocyte maturation" pathways may be related to the occurrence of LUAD. GSE75037 removed 8 outlier and obtained 2909 differentially expressed genes (DEGs), 26 genes (9 genes in the brown module, 17 genes in the magenta module) overlap with key genes in the driver module. The results of the survival analysis suggest that 19 genes were significantly correlated with the patient's survival time, including KPNA2, FEN1, RRM2, TOP2A, CENPF, MCM4, BIRC5, MELK, MAD2L1, CCNB1, CCNA2, KIF11, CDKN3, NUSAP1, CEP55, AURKA, NEK2, KIF14 and CDCA8, which may be potential biomarkers or therapeutic targets for LUAD. In this study, we provide a theoretical basis for further understanding the biological mechanism of LUAD through bioinformatics analysis of LUAD. [ABSTRACT FROM AUTHOR]

Context.--Rapid advances in the fields of biophotonics, computer science, and instrumentation have allowed for high-resolution imaging of biologic tissues. Objective.--To evaluate the quality of images from an optimized confocal fluorescence microscopy (CFM) platform for rapid evaluation of small fragments of tissue, compared with hematoxylin-eosin staining. Design.--Tissue fragments (up to 1.0 3 0.3 cm) were stained with 0.6 mM acridine orange for 60 seconds and imaged using a CFM platform at 488-nm and 785-nm wavelength. The imaged tissues were then fixed in formalin and processed to generate hematoxylin-eosin--stained tissue sections. The quality of CFM images was scored on a scale of 0 to 3 on the basis of the percentage of the CFM images with recognizable tissue architecture (0, 0%; 1, <20%; 2 20%-50%; 3 >50%). The diagnoses made using CFM images were compared with those made using histopathologic analysis of the hematoxylin-eosin--stained tissue sections. Results.--We imaged 118 tissue fragments obtained from 40 breast, 23 lung, 39 kidney, and 16 liver surgical excision specimens. We acquired CFM images in 2 to 3 minutes; 95.8% (113 of 118) of images showed a quality score of 3, and 4.2% (5 of 118) had a score of 2. We achieved a sensitivity of 95.5%, specificity of 97.3%, positive predictive value of 95.5%, and negative predictive value of 97.3%. Conclusions.--Our results demonstrate the suitability of the CFM platform for rapid and accurate evaluation of small tissue fragments in surgical pathology practice. [ABSTRACT FROM AUTHOR]

Highlights • Proposed approach is used to analyze shape changes of lung lesions over time. • Our methodology uses dynamic shape features to quantify changes of lung lesions. • Provide the specialist bigger support in studies on the biological activity of pulmonary nodules. Abstract Lung cancer remains one of the highest occurring cancers worldwide. Temporal assessment is a useful tool for analyzing the malignant behavior of a lesion during treatment, or for classifying previously unclassified lesions. This paper provides relatively detailed information about the changes in lesions, complementing the results of studies on the biological activity of pulmonary nodules. The methodology presented uses dynamic shape features (DSF) to quantify and analyze the changes in lung lesions over time as detected in computed tomography (CT) images. The study was conducted using two chest CT databases: the Public Lung Database (PLD), which contains images of lesions undergoing evaluation related to the patient's drug therapy, and a private database of images of lung lesions of undetermined diagnosis. The DSF parameters presented variance values in the range from 8.66 × 10 − 05 to 2.58 × 1006 in lesions in images in the private database, and in the range from 6.72 × 10 − 04 to 5.90 × 1010 in lesions images in the PLD. [ABSTRACT FROM AUTHOR]

Background: Sitting time and physical activity may be modifiable determinants of lung function. The purpose of this study was to assess the effect that replacing various movement behaviours has on lung function among individuals with and without obstructive lung disease. Data and methods: For analysis, data were used from participants of the Canadian Longitudinal Study on Aging, recruited between 2012 and 2015. Lung function was assessed using spirometry. A modified version of the Physical Activity Scale for the Elderly was used to assess sitting time and physical activity levels. Isotemporal substitution analysis was performed to analyze the effects of replacing 30 minutes per day of one movement behaviour with another, keeping the total time constant. Analyses were run separately for individuals with an obstructive lung disease (asthma, chronic obstructive pulmonary disease, or forced expiratory volume in 1 second [FEV1] < 5th percentile lower limit of normal,n=3,398), and healthy adults (n=14,707). Results: When sitting time was replaced with 30 minutes per day of any type of physical activity or sleep, an increase in percent (%) of predicted FEV1 (i.e., β=0.65, confidence interval [CI]: 0.43, 0.88 for replacing sitting time with strenuous or strengthening activity) was observed among healthy adults. Among adults with obstructive lung disease, replacing 30 minutes per day of sitting time or sleep duration with strenuous or strengthening activity was associated with an improvement in the percent of predicted FEV1 (i.e., β=0.98, CI: 0.13, 1.82 for replacing sleep duration with strenuous or strengthening activity). Interpretation: Replacing sitting time with physical activity leads to significant improvements in lung function among adults with an obstructive lung disease, as well as among adults without a respiratory disease. [ABSTRACT FROM AUTHOR]

Objective: Convex probe endobronchial ultrasound (EBUS)‐guided transbronchial needle aspiration (TBNA) is a minimally invasive technique with high sensitivity in the mediastinal staging of non‐small cell carcinoma (NSCLC). In recent years, molecular testing has been developed to study genetic mutations in NSCLC. There are studies revealing improved survival in advanced NSCLC using targeted therapy as the first‐line treatment in these patients. The aim of this study was to evaluate the adequacy of EBUS‐TBNA in providing adequate size specimens for EGFR, ALK and ROS1 genetic mutation analysis in patients with adenocarcinoma or not otherwise specified (NOS) lung cancer. Materials and Methods: Charts of patients diagnosed with lung adenocarcinoma or NOS via EBUS‐TBNA were retrospectively reviewed. Information on patient demographics, number of lymph nodes sampled, their size and location, targeted gene mutations and the adequacy of the material sampled for the molecular testing was recorded. Results: A total of 114 patients were included in the study, adenocarcinoma 86 (75%) and NOS 28 (25%). EGFR gene mutation was studied in all of the patients included in the study while ALK in 113 and ROS1 in 98. The material adequacy ratios for EGFR gene mutation, ALK and ROS1 rearrangements were found to be 88.6%, 93.8% and 91.8%, respectively. EGFR gene mutation, ALK and ROS1 rearrangements were found positive in 13 (11.4%), 9 (8%) and 1 (1%) patients, respectively. Conclusion: The study demonstrated that EBUS‐TBNA provides adequate material for mutation analysis in patients with newly diagnosed adenocarcinoma or NOS lung cancer. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is autosomal recessive disease that affects multiple body systems. CF patients often experience sleep disturbances, altered sleep patterns, and sleep apnea. Sleep in mammals is controlled in part by circadian clock genes, including Clock, Bmal1, Period1, Period2, Cryptochrome1, and Cryptochrome2. The purpose of this study was to gain a better understanding of the biological underpinnings of disordered sleep experienced in CF. To accomplish this, we evaluated circadian clock gene expression profiles in CF and wildtype mice, divided into two subgroups each based on sleep condition. One subgroup of each genotype was permitted to maintain their sleep-wake cycle while the other was deprived of sleep for six hours prior to sacrifice. Brain, skeletal muscle, jejunum, colon, lung and adipose tissues were collected from each mouse. Quantitative polymerase chain reaction (PCR) was used to quantify expression of Clock, Bmal1, Period1, Period2, Cryptochrome1 and Cryptochrome2, and expression levels were compared between study groups. Our comparisons showed distinct differences between the CF groups and the wildtype groups under both sleep conditions. Additionally, we found the CF mice that had been sleep deprived had severely dysregulated expression of all measured genes in the lung apart from Cry1. Our findings suggest that (1) disordered sleep in CF may be caused by circadian system dysregulation and (2) the loss of the cystic fibrosis transmembrane conductance regulator (CFTR) is a causative factor in the dysregulated circadian clock gene expression profiles of CF mice. [ABSTRACT FROM AUTHOR]

Synthetic α -tocopherol has eight isomeric configurations including four 2R (RSS , RRS , RSR , RRR) and four 2S (SRR , SSR , SRS , SSS). Only the RRR stereoisomer is naturally synthesised by plants. A ratio of 1·36:1 in biopotency of RRR - α -tocopheryl acetate to all - rac - α -tocopheryl acetate is generally accepted; however, studies indicate that neither biopotency of α -tocopherol stereoisomers nor bioavailability between them is constant, but depend on dose, time, animal species and organs. A total of forty growing young male mink were, after weaning, assigned one of the following treatments for 90 d: no α -tocopherol in diet (ALFA_0), 40 mg/kg RRR - α -tocopheryl acetate (NAT_40), 40 mg/kg all - rac-α -tocopheryl acetate (SYN_40) and 80 mg/kg feed all - rac-α -tocopheryl acetate (SYN_80). Mink were euthanised in CO2 and blood was collected by heart puncture. Mink were pelted and liver, heart, lungs, brain and abdominal fat were collected for α -tocopherol stereoisomer analysis. The proportion of RRR - α -tocopherol decreased in all organs and plasma with increasing amount of synthetic α -tocopherol stereoisomers in the diet (P ≤0·05), whereas the proportion of all synthetic α -tocopherol stereoisomers increased with increasing amount of synthetic α -tocopherol stereoisomers in the diet (P ≤0·05). The proportion of α -tocopherol stereoisomers in plasma, brain, heart, lungs and abdominal fat showed the following order: RRR > RRS , RSR , RSS >Σ2 S , regardless of α -tocopherol supplement. The liver had the highest proportion of Σ2 S stereoisomers, and lowest proportion of RRR - α -tocopherol. In conclusion, distribution of α -tocopherol stereoisomers differs with dose and form of α -tocopherol supplementation. The results did also reveal the liver's role as the major organ for accumulation of Σ2 S α -tocopherol stereoisomers. [ABSTRACT FROM AUTHOR]

Introduction: Patients with severe malaria or sepsis are at risk of developing life-threatening acute respiratory distress syndrome (ARDS). The objective of this study was to evaluate point-of-care lung ultrasound as a novel tool to determine the prevalence and early signs of ARDS in a resource-limited setting among patients with severe malaria or sepsis. Materials and methods: Serial point-of-care lung ultrasound studies were performed on four consecutive days in a planned sub study of an observational cohort of patients with malaria or sepsis in Bangladesh. We quantified aeration patterns across 12 lung regions. ARDS was defined according to the Kigali Modification of the Berlin Definition. Results: Of 102 patients enrolled, 71 had sepsis and 31 had malaria. Normal lung ultrasound findings were observed in 44 patients on enrolment and associated with 7% case fatality. ARDS was detected in 10 patients on enrolment and associated with 90% case fatality. All patients with ARDS had sepsis, 4 had underlying pneumonia. Two patients developing ARDS during hospitalisation already had reduced aeration patterns on enrolment. The SpO2/FiO2 ratio combined with the number of regions with reduced aeration was a strong prognosticator for mortality in patients with sepsis (AUROC 91.5% (95% Confidence Interval: 84.6%-98.4%)). Conclusions: This study demonstrates the potential usefulness of point-of-care lung ultrasound to detect lung abnormalities in patients with malaria or sepsis in a resource-constrained hospital setting. LUS was highly feasible and allowed to accurately identify patients at risk of death in a resource limited setting. [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance In Asia, Jin Gui Shen Qi Wan (JGSQW) has been used for hundreds of years to treat asthma. Aim of the study The traditional Chinese medicine JGSQW is composed of Rehmannia glutinosa , Dioscorea opposita , Cornus officinalis , Poria cocos , Paeonia suffruticosa , Alisma orientalis , Aconitum carmichaelii and Cinnamomum cassia. However, the immunological mechanism underlying the effect of JGSQW treatment on asthma remains unclear. This study examined whether JGSQW has the potential to reduce asthma symptoms in mice with chronic asthma induced by recurrent Dermatophagoides pteronyssinus (Der p) stimulation, as well as its immunoregulatory mechanisms. Materials and methods The airways of BALB/c mice were stimulated with Der p (i.t.) once per week (50 μL, 1 mg/mL) for 6 consecutive weeks, and the mice were fed JGSQW (1 g/kg) 30 min prior to the Der p stimulation. Three days after the last stimulation, the mice were sacrificed to evaluate the airway remodelling, infiltration of inflammatory cells, lung histological features, and total IgE in the blood. Additionally, after A549 cells were treated with JGSQW, loganin, or paeoniflorin for 30 min, 10 ng/mL IL-1β was added to stimulate the A549 cells to evaluate the effect of the medicine on the ICAM-1 gene expression after IL-1β stimulation. Results JGSQW significantly reduced the Der p-induced infiltration of inflammatory cells into airways and decreased the total IgE and Der p-specific IgG1 in serum. Collagen assays and histopathological examinations showed that JGSQW reduced lung airway remodelling. Additionally, an electrophoretic mobility shift assay and immunohistochemical staining verified that JGSQW inhibited the NF-kB expression in airway epithelial cell nuclei. JGSQW, loganin, and paeoniflorin inhibited the ICAM-1 gene expression caused by the IL-1β stimulation of A549 cells, and loganin and paeoniflorin had the maximum inhibitory effect when mixed according to the combination of doses in JGSQW. Conclusion These results indicated that in the chronic asthma mouse model, JGSQW inhibits the infiltration of inflammatory cells into the airways and airway remodelling and exhibits specific immunoregulatory effects. JGSQW with certain doses of loganin and paeoniflorin inhibited ICAM-1 gene expression in epithelial cells. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Background: Current guidelines for lung cancer screening increased a positive scan threshold to a 6 mm longest diameter. We extracted radiomic features from baseline and follow‐up screens and performed size‐specific analyses to predict lung cancer incidence using three nodule size classes (<6 mm [small], 6‐16 mm [intermediate], and ≥16 mm [large]). Methods: We extracted 219 features from baseline (T0) nodules and 219 delta features which are the change from T0 to first follow‐up (T1). Nodules were identified for 160 incidence cases diagnosed with lung cancer at T1 or second follow‐up screen (T2) and for 307 nodule‐positive controls that had three consecutive positive screens not diagnosed as lung cancer. The cases and controls were split into training and test cohorts; classifier models were used to identify the most predictive features. Results: The final models revealed modest improvements for baseline and delta features when compared to only baseline features. The AUROCs for small‐ and intermediate‐sized nodules were 0.83 (95% CI 0.76‐0.90) and 0.76 (95% CI 0.71‐0.81) for baseline‐only radiomic features, respectively, and 0.84 (95% CI 0.77‐0.90) and 0.84 (95% CI 0.80‐0.88) for baseline and delta features, respectively. When intermediate and large nodules were combined, the AUROC for baseline‐only features was 0.80 (95% CI 0.76‐0.84) compared with 0.86 (95% CI 0.83‐0.89) for baseline and delta features. Conclusions: We found modest improvements in predicting lung cancer incidence by combining baseline and delta radiomics. Radiomics could be used to improve current size‐based screening guidelines. We demonstrated that combining delta radiomics with baseline radiomics generally improved the performance statistics to predict lung cancer incidence when compared to using only baseline radiomic features. We note inconsistent results in the performance statistics when we comparing overall models compared to models based on nodule size. As such, our findings suggest there is a trade‐off in terms of performance using nodule size‐specific models vs. an overall model. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Dilodendron bipinnatum Radlk., Sapindaceae, a tree of the Mato Grosso Pantanal , is popularly known as “mulher-pobre”. The decoction or infusion of its inner stem bark is used for treating inflammatory conditions. Aim of the study To determine if a 70% hydroethanolic extract of Dilodendron bipinnatum stem bark (HEDb) is able to reduce allergic airway inflammation in a murine model of ovalbumin (OVA)-induced allergic asthma. Material and methods The inner stem bark powder was macerated in a 70% hydroethanolic solution (1:3 w/v) to obtain HEDb. The induction of experimental asthma was accomplished as follows: on days 1 and 10, Swiss mice were sensitized by an intraperitoneal injection of OVA (100 µg/mL) and aluminum hydroxide (10 µg/mL). From day 19 to 24, animals (n = 6/per group) were treated (p.o.) twice a day with either vehicle (distilled water), HEDb (20, 100 and 500 mg/kg) or dexamethasone (0.5 mg/kg). Sham group animals were intraperitoneally injected and challenged with saline solution (0.9%) instead of OVA and received distilled water orally instead of HEDb, whereas the other groups were challenged with OVA (3% in saline) by aerosolization. On day 25, bronchoalveolar lavage fluid (BALF) was collected for the quantification of total leukocytes, neutrophils, eosinophils, mononuclear cells and Th2 cytokines (IL-4, IL-5, and IL-13). The lungs were collected for histopathological analysis and blood was assayed to determine serum IgE levels. The anti-inflammatory activity of HEDb was additionally confirmed by a lipoxygenase (LO) inhibitory assay in vitro. Results Compared to the sham group, the OVA group showed significantly greater numbers of total leukocytes, neutrophils, eosinophils, and mononuclear cells, as well as inflammatory cytokines in BALF, and also IgE in the serum. HEDb treated mice showed a significant decrease in inflammatory cell accumulation in BALF, with the maximum response observed at 500 mg/kg. Furthermore, the levels of IL-4, IL-5 and IL-13 in BALF, and of IgE in serum, were also considerably reduced as compared to the OVA group. The histopathological examination of the lungs of mice in the vehicle group showed a significant increase in hemorrhagic damage, mucus, perivascular and peribronchial inflammatory cell infiltrates, as well as mast cell degranulation compared to sham. HEDb (100 and 500 mg/kg) remarkably decreased all these parameters, presenting at the highest dose an anti-inflammatory effect comparable to that of dexamethasone (0.5 mg/kg). HEDb also had notable direct anti-inflammatory properties demonstrated by the inhibition of 15-LO activity in vitro (IC 50 = 1.0–5.0 µg/mL). Conclusions These results somewhat agree on the popular use of the inner stem bark of D. bipinnatum as a treatment for allergic asthma. The HEDb exhibits significant anti-inflammatory activity in the OVA-induced mouse model of allergic asthma, possibly due to the down-regulation of the Th2 responses and LO inhibition, resulting in improvements in all analyzed inflammatory parameters. [ABSTRACT FROM AUTHOR]

A standardized in vitro system of human lung cells (A459) in RPMI medium is beneficial for investigations concerning the toxicity of inhalable biopersistent fibrous or granular dusts such as asbestos or titanium dioxide. However, the use of non-biopersistent (soluble) dusts such as aluminum sulfate or aluminum chloride revealed an undesirable precipitate in the cell culture system. In contrast, under the same condition, the soluble dust aluminum citrate did not form any precipitate. The precipitate could be identified as aluminum phosphate by the use of electron microscopy, TG and DSC. Further examinations showed that the composition of the precipitate depends on the admitted quantity of aluminum sulfate or aluminum chloride, respectively. For example, at low dosages, besides aluminum phosphate calcium phosphate can also be detected. Furthermore, the composition of the precipitate (especially the content of crystal water) is modified by aging processes. Phosphate as well as calcium ions are ingredients of the RPMI medium (nutrient solution) and hamper the investigation of soluble aluminum-containing dusts in standardized A459 lung cell system. [ABSTRACT FROM AUTHOR]