Histological Changes In Lungs Research Articles

High expression of miR-483-5p aggravates sepsis-induced acute lung injury.

Sepsis-induced acute lung injury (ALI) has high morbidity and mortality rates, and there remains a need for therapeutic methods to improve the outcome of ALI patients. miR-483-5p is an important regulator for the development of various diseases such as sepsis. Nevertheless, it is not known whether miR-483-5p has an effect on sepsis-induced ALI. To explore this issue, this study used cecal ligation and puncture (CLP)-treated mice and lipopolysaccharide (LPS)-treated pulmonary microvascular endothelial cells (PMVECs) cells to simulate the models of sepsis-induced ALI in vivo and in vitro. Pathological and histological changes of lungs from sepsis-induced ALI mice were detected by Hematoxylin-eosin staining. The detection levels of caspase-3, interleukin (IL)-6 and IL-1β were used to reflect the effect of miR-483-5p on apoptosis and inflammation of sepsis-induced ALI. The detection level of lactate dehydrogenase (LDH) in PMVECs cells was used to reflect the severe extent of sepsis-induced injury. The expression of miR-483-5p in lung tissues of sepsis-induced ALI mice was determined by qRT-PCR. In addition, the interaction of miR-483-5p with PIAS1 was identified and validated by Targetscan website and luciferase reporter assay, respectively. The results showed that miR-483-5p was up-regulated in the lung tissues of sepsis-induced ALI mice. Knockdown of miR-483-5p effectively ameliorated lung injury in mice with sepsis-induced ALI and inhibited inflammation and apoptosis of LPS-treated PMVECs cells. Furthermore, in vitro experiment revealed that PIAS1 was a potential target of miR-483-5p. Moreover, miR-483-5p could suppress PIAS1 expression to aggravate inflammation and apoptosis of LPS-treated PMVECs cells. These findings suggest miR-483-5p is a potential therapeutic and diagnostic biomarker for sepsis-induced ALI and provide a new insight for understanding the molecular mechanism of sepsis-induced ALI.

Evaluation of Human MSCs Treatment Frequency on Airway Inflammation in a Mouse Model of Acute Asthma.

BackgroundStudies in experimental models of allergic asthma have shown that mesenchymal stem cells (MSCs) have therapeutic potential for T-helper 2 (TH2) cell-mediated inflammation. However, the mechanisms underlying these therapeutic effects are not fully understood and their safety has not been confirmed.MethodsUsing a mouse model of experimental allergic asthma, we investigated the efficacy of human adipose-derived mesenchymal stem cells (hADSCs) or human bone marrow-derived mesenchymal stem cells (hBMSCs) according to treatment frequency and timing.ResultsOvalbumin (OVA)-sensitized and -challenged mice exhibited airway hyperresponsiveness (AHR), airway inflammation, and significant increases in TH2 cytokine levels. Both double and single human mesenchymal stem cell (hMSC) treatments significantly decreased AHR and bronchoalveolar lavage fluid counts. In addition, single treatment with hMSCs showed significant attenuation of allergic airway inflammation. However, double treatment with hMSCs during OVA -sensitization and -challenge further increased inflammatory cell infiltration, and TH2 cytokine levels.ConclusionThe results of treatment with hADSCs or hBMSCs suppresses AHR and airway inflammation. However, double hMSC treatment significantly induces eosinophilic airway inflammation and lung histological changes. Therefore, double hMSC treatment is ineffective against asthma and single injection frequency appears to be more important for the treatment of asthma. These results suggest that hMSC therapy can be used for treatment of asthma patients but that it should be used carefully.

Irisin alleviates pulmonary epithelial barrier dysfunction in sepsis-induced acute lung injury via activation of AMPK/SIRT1 pathways

ObjectiveAlveolar epithelial barrier dysfunction in response to inflammatory reaction contributes to pulmonary edema in acute lung injury(ALI).Irisin,a newly-found myokine,exerts the anti-inflammatory effects. This study aims to investigate the protective effects of irisin on lipopolysaccharide (LPS)-induced ALIin vivo and in vitro, and to explore its underlying mechanism. MethodsMale SD rats and A549 cells were divided into 4 groups: control group, LPS group, Irisin pretreated group, and Irisin/Compound C(a special inhibitor of AMPK)-treated group. The ALI model was established by intravenous injection of LPS in rats, and LPS challenge in A549 cells. Pulmonary specimens were harvested for microscopic examination of the pathological changes, and the expression of AMPK,SIRT1,NF-κB, p66Shc and caspase-3 in lung tissues. The pulmonary permeability were examined by wet/dry lung weight ratio(W/D) and lung permeability index(LPI). The apoptotic index, and the expression of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), monocyte chemoattractant activating protein-1 (MCP-1), tight junctions (occludin,ZO-1) were determined both in lung tissue and A549 cells. ResultsIrisin alleviated lung histological changes and decreased pulmonary microvascular permeability in LPS-induced rats. Irisin up-regulated the expression of occludin, ZO-1,AMPK,SIRT1, down-regulated the expression of TNF-α,IL-1β,MCP-1,NF-κB, p66Shc caspase-3, and decreased the apoptotic index in LPS-induced rats and A549 cells. All these protective effects of irisin could be reversed by Compound C. ConclusionIrisin improved LPS-induced alveolar epithelial barrier dysfunction via suppressing inflammation and apoptosis, and this protective effect might be mediated by activating AMPK/SIRT1 pathways.

Inhibition of CD147 Attenuates Stroke-Associated Pneumonia Through Modulating Lung Immune Response in Mice.

Background and Purpose: Acute ischemic stroke triggers a profound systemic and local immunodysfunction that increased the susceptibility to infections, especially stroke-associated pneumonia (SAP). Our previous study has shown that inhibition of CD147 ameliorates acute ischemic stroke, however, the role of CD147 in post-stroke lung infection has not been investigated.Methods: C57BL/6 mice were subjected to transient (60 min) middle cerebral artery occlusion, and treated with anti-CD147 antibody (αCD147). Lung histological changes, vascular permeability, and pulmonary edema were determined. Bacterial burden in the lung tissue and Broncho alveolar lavage fluid (BALF) were measured. Lung leukocyte infiltration, circulating platelet-leukocyte aggregates, cell type-specific IL-17A, and IFN-γ expression in the lung were detected by flow cytometry.Results: CD147 expression was markedly upregulated in the lung after stroke. αCD147 treatment significantly decreased the stroke-associated lung histological damages, bacterial load, vascular permeability and pulmonary edema. The protective effects by αCD147 treatment were associated with deceased lung inflammatory cell infiltration by reducing IL-17A expression in lung γδ T cells and attenuated bacterial load by enhancing IFN-γ expression in the lung NK1.1+ cells and CD4+ T cells. In addition, CD147 expression was also increased in the circulating platelets and leukocytes. Enhanced platelet-leukocyte aggregates following stroke was inhibited by αCD147 treatment.Conclusions: Inhibition of CD147 ameliorates aberrant lung inflammatory and immune response and reduces bacterial infection after stroke. CD147 might represent a novel and promising therapeutic target for post-stroke lung infection.

Mesenchymal stem cells reduce ER stress via PERK-Nrf2 pathway in an aged mouse model.

Mesenchymal stem cells (MSC) have been shown to ameliorate the deleterious effects of bleomycin in murine models. However, the mechanism responsible for protection from pulmonary fibrosis by stem cell therapy is still poorly understood, especially in terms of endoplasmic reticulum (ER) stress. We hypothesized that during bleomycin-induced lung injury, markers of ER stress, specifically the activation of the unfolded protein response (UPR), increase during injury, resembling the kinetics of collagen deposition in the lung described for the bleomycin model. We aimed to elucidate the possible role of MSC in ER stress modulation. To determine the kinetics of ER stress in aged mice, the expression of ER stress markers after bleomycin lung injury was measured in old mice at different time points (days 0, 3, 7, 14 and 21). To evaluate the consequences of systemic delivery of MSC on lung ER stress in the bleomycin model, we evaluated changes in body weight, lung histology and protein expression of ER stress markers. The level of expression of UPR transcription factor XBP-1 and its regulator BiP was elevated at day 7 and progressively increased up to day 21. MSC inhibited BiP expression in bleomycin-induced ER stress, attenuating ER stress via the protein kinase RNA-like ER kinase (PERK)-Nrf2 pathway. The expression levels of other ER stress markers were not perturbed by MSC. Our data suggest that MSC operate on ER stress via several pathways, but the PERK-Nrf2 pathway revealed to be the main functioning pathway in our bleomycin model.

The possible ameliorative role of mesenchymal stem cells and curcumin on the lung in experimentally induced type I diabetes: Histological and immunohistochemical study

Background: Type 1 diabetes mellitus affects lungs due to poor glycemic control. Improvement in both lung function andarchitecture in experimentally-induced lung injury that received exogenous AMSCs by different mechanisms was found.Curcumin has a potent antioxidant and antifibrotic function.Objective: The current study was designed to elucidate the possible ameliorative role of mesenchymal stem cells and curcuminon the lung in experimentally induced type I diabetes by histological and immunohistochemical study.Materials and Methods:Twenty six adult albino rats were divided into five groups: donor, control group, curcumin group andadipose derived mesenchymal stem cell (AMSCs) group. Group II (diabetic group) received a single dose STZ 50 mg/kg/day,group III received STZ and powdered diet supplemented with 0.05% curcumin, group IV received STZ and 1x106 of culturedand labelled rat AMSCs. Lung sections were subjected to histological, morphometric, biochemical and statistical studies.Results: Diabetes induced histological changes in lung in the form of inflammatory changes in bronchiole, a sig increase inthe thickness of interalveolar septa, thickness of the vessels wall, area % of collagen and count CD105+ve cells. Sig decreasein antioxidant activity and sig increase in oxidant enzymes. Sig increase in L-hydroxyproline(L-hyp) level as well STAT andSMAD genes. Administration of curcumin and AMSCs improved sig the previous changes.Conclusion: Diabetes induced lung injuries in rats that was ameliorated by by curcumin, but AMSCs have more pronouncedeffect than curcumin therapy.

Pulegone inhibits inflammation via suppression of NLRP3 inflammasome and reducing cytokine production in mice

Context: Pulegone, a key compound in Schizonepeta essential oil, has been identified as an anti-inflammatory. However, its underlying molecular mechanisms on NLR family pyrin domain containing 3 (NLRP3) inflammasome have not been elucidated.Objective: Here, the modulatory effects of pulegone on NLRP3 inflammasome were investigated.Materials and methods: The C57BL/6J mice were randomly divided into five groups: Normal, Lipopolysaccharides (LPS), Dexamethasone (DEX, 5 mg/kg), Pulegone (0.095 and 0.190 g/kg) groups. All mice were challenged by LPS except for the Normal group.Results: A reduced expression of Interleukin-18 (IL-18), Interleukin-1β (IL-1β), Interleukin-5 (IL-5), Tumor necrosis factor-α (TNF-α), Interferon-gamma (IFN-γ), Monocyte chemoattratctant protein-1 (MCP-1), Macrophage inflammatory protein-1β (MIP-1β), Monocyte colony stimulating factor (M-CSF) and Granulocyte-macrophage colony stimulating factor (GM-CSF) in serum were detected in the pulegone groups as compared to the LPS group. In addition, a reduced mRNA and protein expression production of ASC, NLRP3, and Caspase-1 were detected in lungs after pulegone administration. Histological analysis results indicated that the histological changes of lungs caused by LPS were ameliorated by pulegone. Immunohistochemical study showed a decreased positive cell numbers of P2X7R in Pulegone (0.095 and 0.190 g/kg) groups.Conclusion: Pulegone exerts anti-inflammatory effects on LPS-induced sepsis mice via inhibition of the NLRP3 expression.

Toxoplasma Hypervirulence in the Rat Model Parallels Human Infection and Is Modulated by the Toxo1 Locus.

Toxoplasmosis is considered as an opportunistic parasitic disease. If post-natally acquired in children or adults, it may pass unnoticed, at least with strains of European origin. However, in the wild biotopes especially in South America, Toxoplasma gondii strains display a greater genetic diversity, which correlates to higher virulence for humans, particularly along the Amazon River and its tributaries. In French Guiana, several atypical strains have been associated with severe clinical forms: ocular toxoplasmosis and acute respiratory distress syndrome both of which can result in death. Among these, the GUY008-ABE strain was responsible for an epidemic of severe disseminated toxoplasmosis in Suriname, which led to the death of one immunocompetent individual. To better understand the mechanism underlying the hypervirulence of the GUY008-ABE strain, we have tested the rat model which compared to the mouse, better reflects the immune resistance of humans to Toxoplasma infection. Here we compare the outcome of toxoplasmosis in F344 rats infected either by the GUY008-ABE strain or the type II Prugniaud strain. We show that the GUY008-ABE strain displays a higher virulence phenotype leading to the death of all infected rats observed in this study. GUY008-ABE infection was characterized by an increase of the parasite load in several organs, especially the heart and lung, and was mainly associated with severe histological changes in lungs. Moreover, correlating with its hypervirulence trait, the GUY008-ABE strain was able to form cysts in the LEW rat model otherwise known to be refractory to infection by other Toxoplasma strains. Together, these results show that the rat is a discriminating experimental model to study Toxoplasma virulence factors relevant to the pathogenesis of human infection and that the degree of virulence is linked to the Toxo1 locus.

The protective effect of oleanolic acid on NMDA-induced MLE-12 cells apoptosis and lung injury in mice by activating SIRT1 and reducing NF-κB acetylation

Overactivation of the N-methyl-d-aspartate (NMDA) receptor promotes oxidative stress, aggravates the inflammatory response and induces excitotoxic lung injury. NMDA is a synthetic agonist that selectively activates the NMDA receptor. Oleanolic acid (OA) is a natural anti-inflammatory and antioxidant compound. This study investigated the effect and possible mechanism of OA on NMDA-induced acute lung injury (ALI) in mice. OA pretreatment alleviated NMDA-induced histological lung changes and ameliorated pulmonary oedema and pulmonary permeability. At the same time, OA inhibited inflammatory cell infiltration and decreased the levels of tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in the lung and bronchoalveolar lavage fluid (BALF). OA markedly decreased malondialdehyde (MDA) production and increased the superoxide dismutase (SOD) and glutathione (GSH) contents of the lung in vivo. Meanwhile, we first found that NMDA increased LDH activity and decreased cell viability, and induced oxidative stress and apoptosis in mouse lung epithelial (MLE)-12 cells. By employing SRT1720 and sirtinol, the activator and inhibitor of sirtuin 1 (SIRT1), we found that SRT1720 partially eliminated the increase in ROS，and sirtinol further promoted the increase in ROS caused by NMDA. OA increased MLE-12 cells viability and attenuated oxidative stress after NMDA challenge in vitro. OA suppressed NMDA-induced MLE-12 cells apoptosis, while sirtinol inhibited the effect of OA. In addition, OA significantly upregulated the levels of SIRT1, nuclear-related factor 2(Nrf2) and Bcl-2 protein and downregulated the levels of acetylated nuclear factor-kappa B (NF-κB), NLRP3 and Bax protein. In conclusion, OA attenuated NMDA-induced excitotoxic lung injury, potentially through its anti-inflammatory, antioxidative stress and anti-apoptotic effects. The mechanism may be related to activating SIRT1 and reducing NF-κB acetylation.

The interventional effects of saturated hydrogen saline on lung injury in rats with cecal ligation and puncture operation

To investigate the hypothesis that hydrogen could ameliorate cecal ligation and puncture (CLP)-induced lung injury of rats by inhibiting cystathionine-gamma-lyase/hydrogen sulfide (CSE/H2S) system. A total number of 24 healthy male SD rats weighting 250～300 g were randomly divided into four groups (n=6 in each group): sham operation group(sham group), hydrogen-rich saline control group(H2 group), CLP group and hydrogen-rich saline treatment group(CLP+H2 group). The rats were treated with hydrogen-rich saline or saline 10 min before CLP or sham operation. At 8 h of sham or CLP operation, lung samples were obtained to detect the changes of the CSE/H2S system using biochemical and RT-PCR methods. In order to further confirm the role of H2S during hydrogen improve the lung injury of CLP rats, we also observed the effect of hydrogen-rich saline on the lung injury induced by H2S donor-sodium sodium hydrosulfide (NaHS). Thirty-two healthy male SD rats (250~300 g) were randomly divided into four groups (n=8 in each group): control group, H2S group, H2S+H2 group and H2 group. Saline(10 mg/kg) or NaHS(H2S donor, 56 μmol/kg) was injected intraperitoneally (10 mg/kg) respectively into rats in the control rats or H2S group. For rats in the H2S+H2 and H2 group, hydrogen-rich saline (10 mg/kg) was injected 10 min before saline or NaHS administration. Eight hours after the LPS saline or NaHS administration, lung coefficient, MDA content, and MPO activity were detected. The contents of TNF-α, IL-6 and IL-10 in lung tissue were measured, and the morphological changes of lung tissue were also observed. CSE/H2S system up-regulating were observed in animals exposed to CLP. Hydrogen-rich saline treatment significantly inhibited CSE/H2S system as indicated by significantly reduced H2S production in lung, along with a decreased CSE activity and CSE mRNA expression (all P＜0.05). Importantly, the results showed that lung injury and lung tissue inflammation were observed in animals exposed to NaHS. Hydrogen-rich saline treatment significantly attenuated lung injury as indicated by significantly improved histological changes in lung, significantly reduced index of quantitative assessment (IQA), MDA content and lung coefficient (all P＜0.05). MPO activity in lung tissue was significantly reduced along with decreased productions of TNF-α and IL-6, and an increased production of IL-10 in the presence of hydrogen (all P＜0.05), demonstrating antioxidant and anti-inflammatory effect of hydrogen in NaHS-induced ALI. These results indicate that hydrogen-rich saline peritoneal injection improves the lung injury induced by CLP operation. The therapeutic effects of hydrogen-rich saline may be related to suppressing the production of H2S.

Possible protective effect of pomegranate peel powder on lung injury induced by skeletal muscle ischemia-reperfusion

Introduction: Multi-organ failure with life-threatening sequel occurs in a variety of surgical practices as a result of ischemia-reperfusion (I/R) injury.Aim of work: In this study, more light is thrown on the histological lung changes induced by skeletal muscle I/R with reference to their underlying mechanisms and to determine, for the first time, the protective role of pomegranate peel powder on the lung injury induced by skeletal muscle I/R.Materials and Methods: Thirty adult male albino rats were divided equally into three groups: sham control group, I/R group and I/R group pretreated with pomegranate peel powder (500 mg/kg dissolved in distilled water twice daily orally for 10 days). At the end of the experiment, blood samples were obtained to assess serum malondialdehyde (MDA) then lung specimens were processed for routine histological examination and detection of collagen deposition. Myeloperoxidase (MPO), a marker of neutrophils infiltration, transforming growth factor-β (TGF-β), an inflammatory and pro-fibrotic mediator and Bcl2, an anti-apoptotic marker, were detected immunohistochemically.Results: Loss of general architecture of the lung tissues, massive inflammatory infiltrate, emphysema, edema, congested blood vessels, thickened inter-alveolar septa, destruction of some alveoli, disorganization and focal sloughing of the bronchial epithelium in addition to increased collagen deposition were detected in I/R group. Oxidative stress in the form of significant increase of MDA level in addition to up-regulation of both MPO and TGF-β and down-regulation of Bcl2 were implicated in the pathogenesis of acute lung injury induced by skeletal muscle I/R. Pomegranate peel powder significantly ameliorated these damaging effects through its antioxidant, anti-inflammatory, anti-fibrotic and anti-apoptotic effects.Conclusion: Pretreatment of rats with pomegranate peel protected the lungs against skeletal muscle I/R injury.

Histopathological changes and expression of transforming growth factor beta (TGF-β3) in mice exposed to gliotoxin

BackgroundGliotoxin (GT) is the prototype of a class of epipolythiodioxopiperazines (ETPs) which are secondary metabolites made by fungi organisms only e.g., Aspergillus fumigatus, characterized by a disulfide bridge across a piperazine ring with low molecular weight (326 Da),and its sulphur bridge imparts all known toxicity of these molecules. Its name was derived from its identification as a metabolite of Gliocladium fimbriatum as it is previously isolated. It had histopathological effects of human and animals tissues and thus may alter the immune response. ObjectivesThe current study aimed to evaluate the effect of GT on immunological and histological changes in lung, liver, and kidney in addition to morphological changes in colon using animal models. MethodologyMature male BALB/c mice were used in this study, animals were provided by Biotechnology researches center of Al-Nahrain University. To study the histological changes and expression of Transforming growth factor beta (TGF-β3) in mice, animals were injected intraperitoneally (i.p.) with acute dose of both sample and standard gliotoxin with control group (received i.p. one dose of methanol 10%) and the mice of each group were sacrificed at day seven, each mouse was dissected and the organs lung, liver and kidney were collected then sectioned. Mice of another groups were administrated with one dose of sample gliotoxin through the lumen of the colon using a vinyl catheter positioned 5 cm from the anus, and the control group received methanol 10%, the mice were killed on day seven of administration to study the morphological changes in the colon. ResultsGross-examination showed clear pathological changes in examined organs of mice treated intraperitoneally with gliotoxin (i.p.) injection during seven days, lesions were seen in examined organs with groups of all concentrations of both sample and standard gliotoxin in comparing with control. After intrarectal administration, many signs for mycotoxicosis were observed, like shivering, redness around the anus and bristling of hair. Although of the aggressive behavior of mice and loss of activity at the day 6 of treatment was also reduced. In both sample and standard GT groups, the elevation at the high concentrations of the gliotoxin gave over TGF-β3 expression in liver, lung, and kidney. ConclusionsIt can be concluded that both of sample and standard gliotoxin showed the same effectiveness in vivo to induce histopathological changes and the immunohistochemical studies revealed that the increasing of TGF-β3 expression was in a significant relationship between the immunoreactive cell and its intensity with number and size of lesion in the same tissue at probability (P value) < 0.05 level, so further investigations are required to evaluate the acute and /or chronic effect of gliotoxin on other cytokines and further histopathological studies of acute and/or chronic effect of gliotoxin on other organs such as muscles, heart, brain, spleen and intestine are required.

Interleukin-3 plays a vital role in hyperoxic acute lung injury in mice via mediating inflammation

BackgroundInterleukin (IL)-3 amplifies inflammation. However, the effect of IL-3 in acute lung injury (ALI), an acute inflammatory disease, is unclear. The aim of this study was to test the hypothesis that IL-3 plays an important role in hyperoxia-induced ALI.MethodsHyperoxic ALI was induced in wild-type (WT) and IL-3 gene disrupted (IL-3−/−) mice by exposure to 100% O2 for 72 h.ResultsHyperoxia increased IL-3 levels in plasma and lung tissues in WT mice. Pulmonary inflammation and edema were detected by histological assay in WT mice exposed to 100% O2 for 72 h. However, the hyperoxia-induced lung histological changes were improved in IL-3−/− mice. The hyperoxia-induced elevation of neutrophils in bronchoalveolar lavage fluids and circulation were reduced in IL-3−/− mice. Meanwhile, the levels of tumor necrosis factor-α and IL-6 were suppressed in IL-3−/− mice compared with WT mice. Moreover, the hyperoxia-induced the activation of IκBα kinase (IKK) β, IκBα phosphorylation, and nuclear factor-κB translocation were inhibited in IL-3−/− mice compared with WT mice.ConclusionsOur results suggest IL-3 is a potential therapeutic target for hyperoxia-induced ALI.

Pathomorphological changes in lungs of deceased with obesity: review of literature and analysis of own observations.

Background. Obesity is a disease that is characterized by excessive significant harmful effects on the functioning of almost all major systems of the human body. Pathological transformations of the lungs deserve particular attention, given the controversy of literary data relating to pathogenesis and morphological manifestations. The analysis of modern literature shows insufficient quantity and proof of the conducted researches. Objective. To find the morphological changes of the lungs and to establish the dependence of their genesis with the overall obesity by means of a retrospective analysis of protocols of autopsies and necropsy of deceased persons with obesity with the definition of pathomorphological changes of the pulmonary tissue. Methods. The authors analyzed 993 autopsy cases during the year of 2017 on the basis of the Lviv Regional Pathology Bureau. Obesity was detected in 67 death cases, of which 25 cases were randomly selected in order to objectify the detected changes in the lungs. The purposeful study of histological changes in lungs of 25 deceased with obesity has been carried out. Pulmonary tissue has been studied using standard histological techniques – hematoxylin-eosin staining. Results. Among the deceased patients there were 16 (64%) women and 9 (36%) men. The age of the patients ranged from 29 to 90 years. The average age of men was 60.88 ± 5.90; the average age of women was 67.31 ± 3.68. In 5 cases of the general investigation group no pulmonary pathology was detected. Among the 20 cases, the most commonly encountered pathology was pneumosclerosis (17 cases, 68% ). The second, most frequently detected pathology, was chronic bronchitis in the stage of exacerbation or remission (12 cases, 48%). Three cases (12%) were diagnosed with pulmonary thromboembolism: acute - 2 cases and one diagnosed case of recurrent pulmonary thromboembolism. Among other cases, there were pneumonias (3 cases), idiomatic pulmonary fibrosis and squamous cell carcinoma of the lungs. Conclusion. In investigation group of obese deceased, lung diseases were found in 80% of cases. Typical pathomorphological changes of the lungs in obese deceased were diffuse pneumosclerosis (whose correlation with sex and age is not detected) of varying degrees of generalization and chronic bronchitis.

A novel Gallic acid derivative attenuates BLM-induced pulmonary fibrosis in mice

Idiopathic Pulmonary fibrosis is a disease with high morbidity and mortality. Therefore, the development of new drugs is imperative. Gallic acid derivative is a derivative of Gallic acid that can be extracted from Chinese herbal medicine. In previous experiments, we found that Gallic acid derivative played dual roles in inflammatory and antioxidant activities. Meanwhile, Gallic acid derivative could inhibit the proliferation of lung fibroblast. In the present study, we investigated the function of Gallic acid derivative in inhibiting lung fibrosis. 5 mg/kg of bleomycin was administered to mice by a single intratracheal instillation. Three dosages of Gallic acid derivative (75 mg/kg, 150 mg/kg, 300 mg/kg) and Pirfenidone (80 mg/kg) were given to mice for 21 day. Gallic acid derivative treatment significantly reduced lung histological changes and decreased inflammatory cell infiltration. The content of collagen decreased with the decrease of hydroxyproline level. Analogously, the expression of alpha smooth muscle actin was reduced. Gallic acid derivative enhanced the antioxidant status, but reduced the expression of interleukin 6, NADPH oxidase-4. Our study proved that Gallic acid derivative reduced inflammation activation to some extent and could exert its effects through transforming growth factor β1/Smad2 signaling pathway and balancing NOX4/Nrf2.

“POSSIBLE” OR “PROBABLE”. THE NEW APPROACH IN IDIOPATHIC PULMONARY FIBROSIS DIAGNOSIS

The absence of any specific symptoms, variety of radiologic and histologic changes in lungs and often poor physicians experience are the reasons for difficulties in diagnostics of idiopathic pulmonary fibrosis. The diagnostic criteria are constantly being discussed. The basis of this article is The White paper of Fleischner Society (published in “The Lancet Respiratory Medicine” 2017).

The anti-inflammatory and anti-oxidative actions of eugenol improve lipopolysaccharide-induced lung injury

Acute lung injury (ALI) remains a major cause of mortality. In lipopolysaccharide (LPS)-stimulated macrophages, eugenol reduces cyclooxygenase-2 expression, NF-κB activation, and inflammatory mediators. We examined the anti-inflammatory and anti-oxidative action of eugenol in an in vivo model of LPS-induced lung injury. Lung mechanics and histology were analyzed in mice 24 h after LPS exposure, with and without eugenol treatment at different doses. Additional animals, submited to the same protocol, were treated with eugenol at 150 mg/kg to determine its effect on inflammatory cytokines (ELISA) and oxidative markers. LPS-induced lung functional and histological changes were significantly improved by eugenol, in a dose-dependent way. Furthermore, eugenol (150 mg/kg) was able to inhibit the release of inflammatory cytokines (TNF-α, IL-1β and IL-6), NADPH oxidase activity, as well as antioxidant enzymes activity (superoxide dismutase, catalase and glutathione peroxidase). Finally, eugenol reduced LPS-induced protein oxidation. In conclusion, eugenol improved in vivo LPS-induced ALI through both anti-inflammatory and anti-oxidative effects, avoiding damage to lung structure.

Quercetin prevents rhinovirus-induced progression of lung disease in mice with COPD phenotype.

Acute exacerbations are the major cause of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). Rhinovirus, which causes acute exacerbations may also accelerate progression of lung disease in these patients. Current therapies reduces the respiratory symptoms and does not treat the root cause of exacerbations effectively. We hypothesized that quercetin, a potent antioxidant and anti-inflammatory agent with antiviral properties may be useful in treating rhinovirus-induced changes in COPD. Mice with COPD phenotype maintained on control or quercetin diet and normal mice were infected with sham or rhinovirus, and after 14 days mice were examined for changes in lung mechanics and lung inflammation. Rhinovirus-infected normal mice showed no changes in lung mechanics or histology. In contrast, rhinovirus-infected mice with COPD phenotype showed reduction in elastic recoiling and increase in lung inflammation, goblet cell metaplasia, and airways cholinergic responsiveness compared to sham-infected mice. Interestingly, rhinovirus-infected mice with COPD phenotype also showed accumulation of neutrophils, CD11b+/CD11c+ macrophages and CD8+ T cells in the lungs. Quercetin supplementation attenuated rhinovirus-induced all the pathologic changes in mice with COPD phenotype. Together these results indicate that quercetin effectively mitigates rhinovirus-induced progression of lung disease in a mouse model of COPD. Therefore, quercetin may be beneficial in the treatment of rhinovirus-associated exacerbations and preventing progression of lung disease in COPD.

Impact of immunization against OxLDL on the pulmonary response to cigarette smoke exposure in mice

BackgroundCigarette smoke exposure can affect pulmonary lipid homeostasis and cause a progressive increase in pulmonary antibodies against oxidized low-density lipoproteins (OxLDL). Similarly, increased anti-OxLDL antibodies are observed in atherosclerosis, a pathology also tightly associated with smoking and lipid homeostasis disruption. Several immunization strategies against oxidized lipid species to help with their clearance have been shown to reduce the formation of atherosclerotic lesions. Since oxidized lipids are generated during cigarette smoke exposure, we investigated the impact of a prophylactic immunization protocol against OxLDL on the pulmonary effects of cigarette smoke exposure in mice.MethodsMice were immunized systemically with a mixture of human OxLDL (antigen source) and AddaVax (adjuvant) or PBS alone prior to the initiation of acute (2 week) or sub-chronic (8 weeks) cigarette smoke exposure protocols. Anti-OxLDL antibodies were measured in the bronchoalveolar lavage (BAL) fluid and serum by direct ELISA. Pulmonary impacts of cigarette smoke exposure and OxLDL immunization were assessed by measuring BAL inflammatory cells, lung functions, and changes in lung structure and gene levels of matrix/matrix-related genes.ResultsImmunization to OxLDL led to a marked increase in circulating and pulmonary antibodies against OxLDL that persisted during cigarette smoke exposure. OxLDL immunization did not exacerbate or reduce the inflammatory response following acute or sub-chronic exposure to cigarette smoke. OxLDL immunization alone had effects similar to cigarette smoke exposure on lung functions but OxLDL immunization and cigarette smoke exposure had no additive effects on these parameters. No obvious changes in lung histology, airspace or levels of matrix and matrix-related genes were caused by OxLDL immunization compared to vehicle treatment.ConclusionsOverall, this study shows for the first time that a prophylactic immunization protocol against OxLDL can potentially have detrimental effects lung functions, without having additive effects over cigarette smoke exposure. This work sheds light on a complex dynamic between anti-OxLDL antibodies and the pulmonary response to cigarette smoke exposure.

Protocatechuic acid methyl ester modulates fluoride induced pulmonary toxicity in rats

We have found that protocatechuic acid methyl ester (PCAME) attenuates fluoride (F−) toxicity in lung epithelial cells (A549). However, this finding has to be confirmed with in vivo studies. Further, the effect of PCAME on F− induced pulmonary fibrosis and inflammation remains limited. Hence, the present study is aimed to determine the protective effect of PCAME against F− induced pulmonary toxicity in female albino Wistar rats. The animals were treated with sodium fluoride (NaF, 300 ppm in drinking water ad libitum) alone or in combination with PCAME (25 or 50 mg/kg bw/day by oral intubation) for 60 days and analyzed for changes in lung histology, oxidative stress, inflammation, apoptosis and fibrosis markers. PCAME supplementation prevented the F− induced changes in the above markers. Also, altered serum and bronchoalveolar lavage fluid markers and lung histoarchitecture were also restored by PCAME. F− induced modulations in oxidative stress markers, TUNEL positive cells and mRNA levels of inflammatory genes further normalized by PCAME in lung tissues. These results revealed that PCAME effectively attenuated the F− induced changes in the rat lungs by reducing cellular F− accumulation and enhancing antioxidants level. Thus PCAME can be used as a nutraceutical agent for F− toxicity.