Development of a Computational Tool for the Estimation of Alveolar Bone Loss in Oral Radiographic Images

The present study evaluated a newly developed computational tool (CT) to assess the alveolar bone space and the alveolar crest angle and compares it to dentist assessment (GT). The novel tool consisted of a set of processes initiated with image enhancement, points localization, and angle and area calculations. In total, we analyzed 148 sites in 39 radiographic images, and among these, 42 sites were selected and divided into two groups of non-periodontitis and periodontitis. The alveolar space area (ASA) and alveolar crest angle (ACA) were estimated. The agreement between the computer software and the ground truth was analyzed using the Bland–Altman plot. The sensitivity and specificity of the computer tool were measured using the ROC curve. The Bland–Altman plot showed an agreement between the ground truth and the computational tool in all of the parameters assessed. The ROC curve showed 100% sensitivity and 100% specificity for 12.67 mm of the alveolar space area. The maximum percentage of sensitivity and specificity were 80.95% for 13.63 degrees of the alveolar crest angle. Computer tool assessment provides accurate disease severity and treatment monitoring for evaluating the alveolar space area (ASA) and the alveolar crest angle (ACA).

Red Blood Cell-Derived Iron Alters Macrophage Function in COPD

Lung macrophage iron levels are increased in COPD patients. Lung macrophage iron levels are thought to be increased by cigarette smoke, but the role of red blood cells (RBCs) as a source of iron has not been investigated. We investigate RBCs as a potential source of alveolar iron in COPD, and determine the effect of RBC-derived iron on macrophage function. We used lung tissue sections to assess RBC coverage of the alveolar space, iron and ferritin levels in 11 non-smokers (NS), 15 smokers (S) and 32 COPD patients. Lung macrophages were isolated from lung resections (n = 68) and treated with hemin or ferric ammonium citrate (50, 100 or 200 μM). Lung macrophage phenotype marker gene expression was measured by qPCR. The phagocytosis of Non-typeable Haemophilus influenzae (NTHi) was measured by flow cytometry. Cytokine production in response to NTHi in iron-treated macrophages was measured by ELISA. Lung macrophage iron levels were significantly correlated with RBC coverage of the alveolar space (r = 0.31, p = 0.02). Furthermore, RBC coverage and lung macrophage iron were significantly increased in COPD patients and correlated with airflow obstruction. Hemin treatment downregulated CD36, CD163, HLA-DR, CD38, TLR4, CD14 and MARCO gene expression. Hemin-treated macrophages also impaired production of pro-inflammatory cytokines in response to NTHi exposure, and decreased phagocytosis of NTHi (200 μM: 35% decrease; p = 0.03). RBCs are a plausible source of pulmonary iron overload in COPD. RBC-derived iron dysregulates macrophage phenotype and function.

TREM2+ and interstitial macrophages orchestrate airway inflammation in SARS-CoV-2 infection in rhesus macaques

The COVID-19 pandemic remains a global health crisis, yet, the immunopathological mechanisms driving the development of severe disease remain poorly defined. Here, we utilize a rhesus macaque (RM) model of SARS-CoV-2 infection to delineate perturbations in the innate immune system during acute infection using an integrated systems analysis. We found that SARS-CoV-2 initiated a rapid infiltration (two days post infection) of plasmacytoid dendritic cells into the lower airway, commensurate with IFNA production, natural killer cell activation, and induction of interferon-stimulated genes. At this early interval, we also observed a significant increase of blood CD14-CD16+ monocytes. To dissect the contribution of lung myeloid subsets to airway inflammation, we generated a novel compendium of RM-specific lung macrophage gene expression using a combination of sc-RNA-Seq data and bulk RNA-Seq of purified populations under steady state conditions. Using these tools, we generated a longitudinal sc-RNA-seq dataset of airway cells in SARS-CoV-2-infected RMs. We identified that SARS-CoV-2 infection elicited a rapid recruitment of two subsets of macrophages into the airway: a C206+MRC1-population resembling murine interstitial macrophages, and a TREM2+ population consistent with CCR2+ infiltrating monocytes, into the alveolar space. These subsets were the predominant source of inflammatory cytokines, accounting for ~75% of IL6 and TNF production, and >90% of IL10 production, whereas the contribution of CD206+MRC+ alveolar macrophages was significantly lower. Treatment of SARS-CoV-2 infected RMs with baricitinib (Olumiant®), a novel JAK1/2 inhibitor that recently received Emergency Use Authorization for the treatment of hospitalized COVID-19 patients, was remarkably effective in eliminating the influx of infiltrating, non-alveolar macrophages in the alveolar space, with a concomitant reduction of inflammatory cytokines. This study has delineated the major subsets of lung macrophages driving inflammatory and anti-inflammatory cytokine production within the alveolar space during SARS-CoV-2 infection.One sentence summaryMulti-omic analyses of hyperacute SARS-CoV-2 infection in rhesus macaques identified two population of infiltrating macrophages, as the primary orchestrators of inflammation in the lower airway that can be successfully treated with baricitinib

Longer-Term Omega-3 LCPUFA More Effective Adjunct Therapy for Tuberculosis Than Ibuprofen in a C3HeB/FeJ Tuberculosis Mouse Model

Advancement in the understanding of inflammation regulation during tuberculosis (TB) treatment has led to novel therapeutic approaches being proposed. The use of immune mediators like anti-inflammatory and pro-resolving molecules for such, merits attention. Drug repurposing is a widely used strategy that seeks to identify new targets to treat or manage diseases. The widely explored nonsteroidal anti-inflammatory drug (NSAID) ibuprofen and a more recently explored pharmaconutrition therapy using omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs), have the potential to modulate the immune system and are thus considered potential repurposed drugs in this context. These approaches may be beneficial as supportive therapy to the already existing treatment regimen to improve clinical outcomes. Here, we applied adjunct ibuprofen and n-3 LCPUFA therapy, respectively, with standard anti-TB treatment, in a C3HeB/FeJ murine model of TB. Bacterial loads, lung pathology, lung cytokines/chemokines and lung lipid mediators were measured as outcomes. Lung bacterial load on day 14 post-treatment (PT) was lower in the n-3 LCPUFA, compared to the ibuprofen group (p = 0.039), but was higher in the ibuprofen group than the treated control group (p = 0.0315). Treated control and ibuprofen groups had more free alveolar space initially as compared to the n-3 LCPUFA group (4 days PT, p= 0.0114 and p= 0.002, respectively); however, significantly more alveolar space was present in the n-3 LCPUFA group as compared to the ibuprofen group by end of treatment (14 days PT, p = 0.035). Interleukin 6 (IL-6) was lower in the ibuprofen group as compared to the treated control, EPA/DHA and untreated control groups at 4 days PT (p = 0.019, p = 0.019 and p = 0.002, respectively). Importantly, pro-resolving EPA derived 9-HEPE, 11-HEPE, 12-HEPE and 18-HEPE lipid mediators (LMs) were significantly higher in the EPA/DHA group as compared to the ibuprofen and treated control groups. This suggests that n-3 LCPUFAs do improve pro-resolving and anti-inflammatory properties in TB, and it may be safe and effective to co-administer as adjunct therapy with standard TB treatment, particularly longer-term. Also, our results show host benefits upon short-term co-administration of ibuprofen, but not throughout the entire TB treatment course.

Research on Effect of Exosome Excreted by RAW264.7 Cell on Damage of Mice Lung Function and Its Mechanism

The exosome excreted by RAW264.7 cell was found to participate in the damage of lung function. Our purpose was to assess the exact mechanism. The animal experiment was adopted in our study. It was provided reference for clinical experiment. 30 healthy male rats were selected and assigned into normal control group, normal exosome group and LPS with exosome group by random number table followed by analysis of the size and form of exosome under electron microscope, the lung structural change by hematoxylin and eosin staining, TNF-α and IL-1β secretion by immunohistochemistry, and the expression of tightly bound protein one (ZO-1), closed protein, β-chain protein and two groups of exosome-marked protein (CD9 and CD63) by western blot. In normal control group, the lung structure was very integral with clear alveolar space. The cell wall was smooth relatively without exudation substance in alveolar space and mesenchyme. Normal exosome group showed relatively integral lung structure and thicker cell wall. The inside of alveolar space was very clear without exudation substance in alveolar space and mesenchyme. LPS + exosome group presented abundant inflammatory cells in alveolar space and mesenchyme with obvious bleeding. Inflammatory factor secretion such as TNF-α (1.334 ± 0.205%) and IL-1β (0.803 ± 0.097%)was significantly higher and the content of closed protein (0.203 ±0.017%) was lower in LPS with exosome group than the other two groups (P < 0.05). The exosome secreted by RAW264.7 cell after stimulation by lipopolysaccharide could impair the lung function in rats and is related with the decline of closed protein.

Analysis of in dicators of body’s gas exchange in high-altitude flight based on a static model of the respiratory system

The purpose of the research was to analyze the dynamics of indicators of human gas exchange in high-altitude flight on the basis of a static model of the respiratory system of the body. First, we developed the structure of this model and an algorithm for calculating the gas exchange of the body. Next, we analyzed changes in indicators of the function of external respiration and gas exchange, and clarified the quantitative parameters that determine the nature of the relationships between the components of gas exchange. Finally, we carried out a computational experiment to simulate ascent to a height. The results of the analysis of the calculations showed that when a person rises to a height with a drop in pressure, tidal volumes change the volume of the alveolar space decreases and the dead space increases in the ratio from 4.7 to 0.7. An uncompensated respiratory alkalosis develops, leading to a violation of the acid-base reactions of the body.

Comparison of reversal of rat pulmonary fibrosis of nintedanib, pirfenidone, and human umbilical mesenchymal stem cells from Wharton’s jelly

Background The present study compared the effects of antifibrotic medications, pirfenidone, and nintedanib, with transplantation of human umbilical mesenchymal stem cells (HUMSCs) in restoring rat pulmonary fibrosis (PF). Methods A stable animal model was established via an intratracheal injection of 5 mg bleomycin (BLM). One single transplantation of 2.5× 107 HUMSCs or initiation of daily oral nintedanib/pirfenidone administration was performed on day 21 following BLM damage. Results Pulmonary function examination revealed that BLM rats exhibited a significant decrease in blood oxygen saturation and an increase in respiratory rates. While no significant improvements were found in BLM rats receiving nintedanib or pirfenidone, those who transplanted with HUMSCs showed a statistical amelioration in blood oxygen saturation and significant alleviation in respiratory rates. Quantification results revealed that a significant reduction in alveolar space and marked increases in substantial cell infiltration and collagen deposition in the left lungs of BLM rats. No significant alteration was observed in BLM rats administered nintedanib or pirfenidone. However, BLM rats transplanted with HUMSCs had a significant recovery in alveolar space and noticeable decreases in cell infiltration and collagen deposition. The inflammatory cell numbers in the bronchoalveolar lavage was increased in the BLM group. While the rats treated with nintedanib or pirfenidone had a lower cell number than the BLM group, a higher cell number was found as compared with the Normal group. In rats transplanted with HUMSCs, the cell number did not differ from the Normal group. Conclusions Transplantation of HUMSCs could effectively treat PF as opposed to the administration of anti-fibrotic drugs with nintedanib or pirfenidone with a significant better result in lung volume, pathological changes, lung function, and blood oxygen saturation.

Comparison of Reversal of Rat Pulmonary Fibrosis of Nintedanib, Pirfenidone and Human Umbilical Mesenchymal Stem Cells from Wharton’s Jelly

Background:The present study compared the effects of antifibrotic medications, Pirfenidone and Nintedanib, with transplantation of human umbilical mesenchymal stem cells (HUMSCs) in restoring rat pulmonary fibrosis (PF).Methods:A stable animal model was established via an intratracheal injection of 5 mg bleomycin (BLM). One single transplantation of 2.5 107 HUMSCs or initiation of daily oral Nintedanib/Pirfenidone administration was performed on Day 21 following BLM damage.Results:Pulmonary function examination revealed that BLM rats exhibited a significant decrease in blood oxygen saturation and an increase in respiratory rates. While no significant improvements were found in BLM rats receiving Nintedanib or Pirfenidone, those who transplanted with HUMSCs showed statistical amelioration in blood oxygen saturation and significant alleviation in respiratory rates. Quantification results revealed that a significant reduction in alveolar space and marked increases in substantial cell infiltration and collagen deposition in the left lungs of BLM rats. No significant alteration was observed in BLM rats administered Nintedanib or Pirfenidone. However, BLM rats transplanted with HUMSCs had a significant recovery in alveolar space and noticeable decreases in cell infiltration and collagen deposition. The inflammatory cell numbers in the bronchoalveolar lavage was increased in the BLM group. While the rats treated with Nintedanib or Pirfenidone had a lower cell number than the BLM group, a higher cell number was found as compared with the Normal group. In rats transplanted with HUMSCs, the cell number did not differ from the Normal group.Conclusions:Transplantation of HUMSCs could effectively treat PF as opposed to the administration of anti-fibrotic drugs with Nintedanib or Pirfenidone with significant better result in lung volume, pathological changes, lung function and blood oxygen saturation.