Lung Tissue Of Animals Research Articles

Erythropoietin Reduces Inflammation, Oxidative Stress, and Apoptosis in a Rat Model of Bleomycin-Induced Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a lethal interstitial disease with unknown etiology and no effective cure, posing a great health burden to society. Erythropoietin (EPO) has been demonstrated to have protective roles in various tissues such as brain, spinal cord, heart, kidney and lung tissues. In this study, we investigate the specific anti-inflammatory, antioxidant and antiapoptotic effects of erythropoietin on lung tissue in a bleomycin-induced rat model of idiopathic pulmonary fibrosis. Recombinant human EPO or saline was injected, and the animals were monitored for 14 days after bleomycin instillation. Their hematocrit and serum EPO levels were determined. Histological and immunohistochemical analyses were performed. The extent of tissue injury, determined through morphometric analysis, was significantly decreased in size in animals treated with erythropoietin. An immunohistochemical analysis of the expression of cyclooxygenase-2 (COX-2), inducible synthase of nitric oxide (i-NOS), metalloproteinase-9 (MMP-9), erythropoietin receptor (EPO-R), and cytochrome-C (cyt-C) found these enzymes to be decreased in a statistically significant manner in animals treated with erythropoietin when compared to a non-treated group. The reduced expression of COX-2, i-NOS, MMP-9, EPO-R, and i-NOS in the lung tissues of animals treated with EPO indicates the anti-inflammatory, antioxidant and antiapoptotic action of erythropoietin, suggesting its potential therapeutic role in pulmonary fibrosis.

Ssc-miR-101-3p inhibits hypoxia-induced apoptosis and inflammatory response in alveolar type-II epithelial cells of Tibetan pigs via targeting FOXO3

Tibetan pigs are a unique swine strain adapted to the hypoxic environment of the plateau regions in China. The unique mechanisms underlying the adaption by Tibetan pigs, however, are still elusive. Only few studies have investigated hypoxia-associated molecular regulation in the lung tissues of animals living in the plateau region of China. Our previous study reported that ssc-miR-101-3p expression significantly differed in the lung tissues of Tibetan pigs at different altitudes, suggesting that ssc-miR-101-3p plays an important role in the adaptation of Tibetan pigs to high altitude. To understand the underlying molecular mechanism, in this study, the target genes of ssc-miR-101-3p and their functions were analyzed via various methods including qRT-PCR and GO and KEGG pathway enrichment analyses. The action of ssc-miR-101-3p was investigated by culturing alveolar type-II epithelial cells (ATII) of Tibetan pigs under hypoxic conditions and transfecting ATII cells with vectors overexpressing or inhibiting ssc-miR-101-3p. Overexpression of ssc-miR-101-3p significantly increased the proliferation of ATII cells and decreased the expression of inflammatory and apoptotic factors. The target genes of ssc-miR-101-3p were significantly enriched in FOXO and PI3K-AKT signaling pathways required to mitigate lung injury. Further, FOXO3 was identified as a direct target of ssc-miR-101-3p. Interestingly, ssc-miR-101-3p overexpression reversed the damaging effect of FOXO3 in the ATII cells. In conclusion, ssc-miR-101-3p targeting FOXO3 could inhibit hypoxia-induced apoptosis and inflammatory response in ATII cells of Tibetan pigs. These results provided new insights into the molecular mechanisms elucidating the response of lung tissues of Tibetan pigs to hypoxic stress.

Microwave dielectric properties of normal, fibroelastotic, and malignant human lung tissue

Technological development of microwave treatment and detection techniques for lung cancer requires accurate and comprehensive knowledge of the microwave dielectric properties of human lung tissue. We characterize the dielectric properties of room temperature human lung tissue from 0.5 to 10 GHz for three lung tissue groups: normal, fibroelastotic, and malignant. We fit a two-pole Debye model to the measured frequency-dependent complex permittivity and calculate the median Debye parameters for the three groups. We find that malignant lung tissue is approximately 10% higher in relative permittivity and conductivity compared to normal lung tissue; this trend matches previously reported normal versus malignant data for other biological tissues. There is little contrast between benign lung tissue with fibroelastosis and malignant lung tissue. We extrapolate our data from room temperature to 37 °C using a temperature-dependence model for animal lung tissue and use the Maxwell-Garnett dielectric mixing model to predict the dielectric properties of inflation-dynamic human lung tissue; both approximations correspond with previously reported dielectric data of bovine and porcine lung tissue.

Comparative Study of Pathomorphological Changes in Animal Lung Tissue when Modeling Infection Caused by the SARS-CoV-2 Virus

Comparative Study of Pathomorphological Changes in Animal Lung Tissue when Modeling Infection Caused by the SARS-CoV-2 Virus

DYNAMIC CHANGES IN HISTOLOGICAL AND MORPHOMETRIC INDICATORS OF THE LUNGS IN SEXUALLY IMMATURE RATS DURING SIMULATION OF PARTIAL TRACHEAL STENOSIS

Introduction. The morphological features of the respiratory system in laryngomalacia remain insufficiently understood, particularly regarding structural, cytological, and functional alterations. The aim of this study is to investigate the morphological characteristics of the respiratory compartment in the lungs of sexually immature rats, conduct a morphometric assessment of lung tissue density, analyze the dynamics of erythrocyte mass and collagen accumulation, and identify correlations between these parameters. Materials and Methods: The study involved sexually immature male Wistar rats aged 25-28 days and weighing 40-55 g. Partial tracheal stenosis was induced in experimental animals using a developed method, restricting the tracheal lumen by 20-25%. The stenosis was maintained for 7 and 21 days in different groups. In one group, tracheal stenosis was relieved after 7 days by removing the compressive ligature. Histological, histochemical, and morphometric methods were employed to study changes in lung tissue. Results. Pathological changes in lung tissue during hypoxia were characterized by an increase in the number of different types of cells and erythrocyte mass, especially on the 21st day of the experiment and the removal of ligatures from the trachea in experimental animals. Disturbances in the microcirculation of the lung acini were manifested by a sharp increase in blood filling of the microvessels and expansion of their lumen. In this case, the process of erythrocyte penetration into the lumen of the alveoli was sometimes noted. The results of histochemical detection of collagen indicate that in the lung tissue of experimental animals there is no activation of fibrogenetic processes, which would be accompanied by a simultaneous increase in the specific density of collagen. Indicators characterizing the lung tissue (number of cells, their specific density) made it possible to evaluate the corresponding correlations. At the same time, they were not associated with the level of collagen or erythrocyte density in the studied loci of the respiratory system of experimental sexually immature rats. A significant increase in the specific density of erythrocyte mass in lung tissue did not depend on the duration of the experiment. Removal of the ligature and restoration of the tracheal lumen did not significantly affect the restoration of alveolar acini and the spectrum of identified cells. In addition, an increase in the specific density of lung tissue was observed. Conclusion. The findings of this study contribute to deeper understanding of lung damage in children with laryngomalacia and associated respiratory system ventilation impairment. The observed reactive changes in lung connective tissue and collagen synthesis during hypoxia do not necessarily indicate the development of respiratory system fibrosis. However, longer exposure to hypoxic conditions may increase the risk of fibrosis in children.

The effect of oral administration of tauroside Sx1 on the accumulation of influenza virus and histological changes in the lungs of mice

The constant threat of a new viral pandemic gives special urgency to the search for new effective means of preventing and treating influenza infection. The article examines the effect of oral administration of saponin tauroside Sx1, obtained from the leaves of Crimean ivy, on the development of infection caused by influenza virus A/WSN/1/33(H1N1), and histological changes in the lungs of infected mice. It was revealed that oral administration of saponin tauroside Sx1 at a dose of 200 mcg/mouse day or 11.8 mg/kg/day for three days after infection led to an almost twofold statistically significant increase in the average life expectancy of infected animals from 6.50±0.67 to 11.10±2.19 days. The protective activity of tauroside Sx1 was established when administered orally in the early stages of influenza infection in mice. The protective effect of saponin is manifested in a significant increase in the average life expectancy and normalization of the structure of lung tissue in infected animals. The results obtained indicate the prospects for further study of saponin tauroside Sx1 as a potential component of anti-influenza drugs.

Molecular markers of M. tuberculosis virulence in lung tissue (experimental study)

To use a biological model, in order to determine significant molecular immunohistochemical markers characterizing the virulence of the "Buryat" and "Omsk" subtypes of the M. tuberculosis Beijing genotype in lung tissue. Lung samples of the C57BL/6 male mice were obtained during experimental infection with M. tuberculosis strains: the reference laboratory strain H37Rv, multidrug-resistant clinical strains 396 (highly lethal and hypervirulent «Buryat» genotype Beijing 14717-15) and 6691 (low-lethal and low-virulent "Omsk" genotype Beijing 1071-32) on days 14, 21, 60 and 120. They were studied by histological and immunohistochemical methods. The relative areas of expression of IL-6, IL-12A, iNOS, and TNF-α in the lung tissue of model animals were established. A study of strain 396 showed that both disease progression and damage to lung tissue are associated with a highly reactive immune response and increased synthesis of iNOS and strain characteristics that block the production of TNF-α. On the contrary, for strain 6691 a low reactivity of the immune response was revealed, with statistically significantly lower values of the relative area of expression of NOS and TNF-α during all observation periods (days 14-120). All animals that survived to day 120 showed a similar morphological picture with differences in cytokine levels, indicating a nonlinear relationship between proinflammatory factors and the damage substratum. The progression of the disease and damage of lung tissue were associated with a highly reactive immune response and increased synthesis of iNOS, strain properties that block the TNF-α production. Thus, iNOS and TNF-α can act as molecular markers characterizing the virulence of the "Buryat" and "Omsk" subtypes of M. tuberculosis in lung tissue.

Regulation of miRNA-155-5p ameliorates NETosis in pulmonary fibrosis rat model via inhibiting its target cytokines IL-1β, TNF-α and TGF-β1

Idiopathic pulmonary fibrosis (IPF) is an age-related inflammatory disease with no cure up till now.It is accompanied by neutrophils infiltration as the main responders to inflammation and fibrosis. Importantly, neutrophils release neutrophil extracellular traps (NETs) through NETosis process. The function of microRNAs during inflammation became of great biological attention. Owing to microRNAs’ central role in immune system, microRNA-155-5p (miR-155-5p) is intensely involved in the inflammatory response. Capsaicin (Cap) is a bioactive compound that exhibits antioxidative and anti-inflammatory functions. Recent studies have shown its role in regulation of certain microRNAs’ expressions. Accordingly, the present study aims to investigate the effect of miR-155-5p regulation in suppressing NETs production via ameliorating its target inflammatory cytokines, IL-1ß, TNF-α and TGF-ß1, in bleomycin (BLM)-induced pulmonary fibrosis rat model treated by Cap. The obtained results demonstrated that miR-155-5p downregulation was associated with significant decrease in IL-1ß, TNF-α, TGF-β1, which consequently, reduced hydroxyproline (HYP), NETs activity markers as NE and PAD-4, and alleviated CTGF levels in lung tissues of animals treated by Cap. Furthermore, NETosis ultrastructure examination by transmission electron microscope (TEM), MPO immunohistochemical staining and histopathological studies confirmed an abolishment in NETs formation and an improvement in lung tissue architecture in Cap-treated rats. This study concluded that Cap quenched the inflammatory response through interrupting IL-1β, TNF-α and TGF-β1 pathway via modulating miR-155-5p expression. In addition, Cap was able to alleviate pulmonary NETosis markers by restraining NETs activity markers. These findings provide novel insight into the application of Cap-based treatment in ameliorating pulmonary damage in IPF.

EXPERIMENTAL AND MORPHOLOGICAL JUSTIFICATION OF THE ENTERAL INSUFFICIENCY DEVELOPMENT IN ABDOMINAL SEPSIS

Abstract. Abdominal sepsis continues to remain the most frequent and formidable complication that complicates the course of acute surgical diseases of the abdominal cavity in 15-25 % of cases, and the mortality rate in various forms of peritonitis, depending on the form and its spread, is from 4 % to 60 %, reaching 90 % in postoperative peritonitis.The aim of the study. To study the dynamics of morphological changes of internal organs in animals with simulated acute diff use peritonitis, depending on the stage of the infl ammatory process of the peritoneum.Material and methods. The object of experimental research was 54 white sexually mature non-linear rats weighing 0.18-0.20 kg, kept in the vivarium of the Bukovinian State Medical University, which were divided into two groups. The main group consisted of 28 animals that were simulated with abdominal sepsis. Control group – 26 intact rats. All animals had free access to food and water. Abdominal sepsis in rats was modeled according to our proposed method, which consisted in infecting the peritoneal cavity with the contents of the hollow organs of the abdominal cavity. Animals were removed from the experiment on 1, 3, and 7 days of simulated peritonitis by decapitation under thiopental anesthesia.The results. On the fi rst day of simulation of peritonitis in the animals of the main group, a histological examination of the peritoneum revealed focal purulent peritonitis with damage to the parietal peritoneum. Diff use hyperemia, focal edema of the connective tissue, which is most developed in the submesothelial layers, was observed. Areas of swollen connective tissue contain a slight but diff use mononuclear infl ammatory infi ltrate. We did not detect morphofunctional changes in the liver and kidneys of animals of the main group on the fi rst day of experimental peritonitis. However, already on the third day of the study, the structure of the liver lobe was only partially preserved. The central veins were well visualized, slightly dilated, and contained a small number of erythrocytes. Changes were also found in the lung tissue of animals with peritonitis: enlarged alveoli and congestion of small vessels and hemorrhages. Hemorrhagic syndrome is not excluded as an early manifestation of acute pulmonary insu ffi ciency. On the seventh day, the structure of the liver lobe was signifi cantly disturbed in the animals. The central veins were well visualized, slightly dilated and contained a large number of erythrocytes. Sinusoids were not visualized in the vast majority of fi elds of view, sometimes they were detected only centrilobularly. The beam organization of hepatocytes was disturbed throughout the size of the lobule. During the histological examination of the kidney tissue of the animals on the 7th day of Клінічна анатомія та оперативна хірургія – Т. 22, № 4 – 2023 27 the experiment, we observed that in the cortical layer of the kidney, the glomeruli were somewhat enlarged and dilated, their vessels were fi lled with blood, serous exudate was observed in the lumens, and individual glomeruli were shrunken and collapsed. The vessels of the venous bed were somewhat dilated, full of blood, and small perivascular spot hemorrhages were visualized.Conclusion. Morphological changes occur already during the reactive phase of abdominal sepsis and indicate the stages of multiple organ failure syndrome.

Interleukin-41 diminishes cigarette smoke-induced lung inflammation in mice

BackgroundChronic obstructive pulmonary disease (COPD) and other inflammatory lung illnesses are markedly exacerbated by cigarette smoke (CS). The novel cytokine interleukin (IL)-41 has immunoregulatory effects, but data on its function in lung inflammation caused by CS are limited and inconclusive. Our study aimed to investigate the ability of IL-41 to protect against CS-induced lung inflammation in vivo. MethodsIn this model, mice were exposed to six cigarettes three times daily for 1 h, with 4-hour intervals between exposures, for 5 consecutive days. Mice received an intraperitoneal dose of IL-41 or a negative control 1 day prior to their initial exposure to CS. On day 6, mice were sacrificed to assess the impact of IL-41 on CS-induced lung inflammation. ResultsWe found that IL-41 pre-treatment alleviated pulmonary inflammatory infiltration and lung tissue lesions. IL-41 pre-treatment also limited CS-induced weight loss, and resulted in lower numbers of macrophages in the bronchoalveolar lavage fluid and lower percentages of neutrophils and monocytes in the blood. Furthermore, it promoted the polarization of M2 macrophages rather than M1 macrophages, as determined by immunohistochemistry. Consistent with its effects on M2 polarization, pre-treatment with IL-41 was associated with higher levels of IL-10 in the bronchoalveolar lavage fluid and lung tissues of CS-exposed animals and lower production of tumor necrosis factor-α, IL-6 and IL-1β in the serum and lung tissues. ConclusionsThese findings suggest that IL-41 could be used therapeutically to treat CS-induced lung inflammatory disorders as it inhibits CS-induced pulmonary inflammation when administered in vivo in mice.

Limosilactobacillus fermentum modulates the gut-airway axis by improving the immune response through FOXP3 activation on combined allergic rhinitis and asthma syndrome (CARAS)

Combined allergic rhinitis and asthma syndrome (CARAS) is an allergic airway inflammatory disorder orchestrated by the type 2 immune response. The close gut-lung relationship has been described, however, the effect of gut-modulating agents such as probiotics in allergic airway disorder is unclear. Thus, the goal of this study was to evaluate theLimosilactobacillus fermentumsupplementation in animals with CARAS. Therefore, BALB/c mice were ovalbumin (OVA) -sensitized and -challenged after being supplemented withL. fermentum. Animals, previously probiotic supplemented, showed a decrease (p < 0.05) of inflammatory cell migration, mainly eosinophil, into the nasal (NALF) and the bronchoalveolar (BALF) fluids as well as reduction of the allergic signs such as sneezing, nasal rubbings, and nasal hyperreactivity induced by histamine as compared with non-supplemented animals. In the systemic context,L. fermentumreduced eosinophilia and the serum levels of OVA-specific IgE. The altered histological aspects of nasal and lung tissues of animals with CARAS were effectively ameliorated byL. fermentum. In the BALF, the immunomodulatory effect was due to the decreasing of type 2 and 3 cytokines (IL-4, IL-13, IL-5 and IL-17A) dependent on type 1 (IFN-γ) and Treg (IL-10) cytokine increasing. Indeed,L. fermentumimproved the FOXP3 activation. Additionally, these effects correlate with the amplification of the gut response as increasing short-chain fatty acids (SCFAs) levels, gut epithelium barrier (ZO-1) maintenance, and colon tissue integrity. These data pointed out that animals’ probiotic supplemented presented immunomodulatory responses in CARAS experimental model by activating the intracellular transduction signal underlying the IL-10 gene transcription.

Structural and functional characteristics of the pulmonary hemomicrocirculatory bed in induced systemic sclerosis: an experimental study.

The objective of this study was to investigate the effects of prolonged exposure to the oxidative agent NaClO on histopathological changes in the lung tissues of laboratory animals. Specifically, the study aimed to examine morphological changes in the pulmonary microcirculation and the level of vascular cell adhesion molecule-1 (VCAM-1) as a functional activity indicator of endothelial cells in animals with induced systemic sclerosis (SSc). A laboratory animal model was used to assess the impact of long-term exposure to NaClO on lung tissues. The animals were divided into three groups: the experimental group (25 rats) was exposed to NaClO, while the control group (20 rats) received an isotonic solution, and the intact group (15 animals) was without any exposure. The concentration of VCAM-1 in the serum of the animals was measured using an enzyme-linked immunosorbent assay. Histopathological analysis of lung tissue specimens was performed using both light and electron microscopy. The concentration of VCAM-1 in the serum of the animals in the experimental group was significantly higher than that of the control group (91.25 [85.63-143.75] vs 19.50 [13.53-22.20], p < 0.05). The histopathological analysis revealed significant abnormalities in the lung tissue specimens from the experimental group, including disruption in the structure of the hemocapillaries of the lungs, narrowing of the microvessel lumen, and perivascular infiltration by polymorphonuclear cells. The electron microscopic analysis showed several ultrastructural changes in the endotheliocytes of the hemocapillaries, including uneven expansion of the perinuclear space, swollen mitochondria, and fragmentation of the membranes of the granular endoplasmic reticulum. Additionally, the basement membrane of hemocapillaries showed uneven thickening with indistinct contours, and the peripheral parts of endotheliocytes were marked by numerous micropinocytotic vesicles and vacuoles. Erythrocyte aggregates and leukocyte adhesion were identified in the lumen of many hemocapillaries, while adhesion and aggregation of platelets were also observed in several hemocapillaries. Long-term exposure to NaClO can cause significant histopathological changes in lung tissues, including damage to the hemocapillaries and disruption in the structure of endotheliocytes.

The miR-15b-Smurf2-HSP27 axis promotes pulmonary fibrosis

BackgroundHeat shock protein 27 (HSP27) is overexpressed during pulmonary fibrosis (PF) and exacerbates PF; however, the upregulation of HSP27 during PF and the therapeutic strategy of HSP27 inhibition is not well elucidated.MethodsWe have developed a mouse model simulating clinical stereotactic body radiotherapy (SBRT) with focal irradiation and validated the induction of RIPF. HSP25 (murine form of HSP27) transgenic (TG) and LLC1-derived orthotropic lung tumor models were also used. Lung tissues of patients with RIPF and idiopathic pulmonary fibrosis, and lung tissues from various fibrotic mouse models, as well as appropriated cell line systems were used. Public available gene expression datasets were used for therapeutic response rate analysis. A synthetic small molecule HSP27 inhibitor, J2 was also used.ResultsHSP27 expression with its phosphorylated form (pHSP27) increased during PF. Decreased mRNA expression of SMAD-specific E3 ubiquitin-protein ligase 2 (Smurf2), which is involved in ubiquitin degradation of HSP27, was responsible for the increased expression of pHSP27. In addition, increased expression of miRNA15b was identified with decreased expression of Smurf2 mRNA in PF models. Inverse correlation between pHSP27 and Smurf2 was observed in the lung tissues of PF animals, an irradiated orthotropic lung cancer models, and PF tissues from patients. Moreover, a HSP27 inhibitor cross-linked with HSP27 protein to ameliorate PF, which was more effective when targeting the epithelial to mesenchymal transition (EMT) stage of PF.ConclusionsOur findings identify upregulation mechanisms of HSP27 during PF and provide a therapeutic strategy for HSP27 inhibition for overcoming PF.

Age-related changes in lung function in National Center for Geriatrics and Gerontology Aging Farm C57BL/6N mice.

Aging is an extremely complex biological process, and various models, from unicellular organisms to mammals, have been used in its research. The mouse is the most widely used model for studying human aging and diseases due to its high homology and well-established strategies for genetic manipulation. Despite these advantages, the maximum lifespan of laboratory mice is nearly three years, which makes it time-consuming to obtain animals of the desired age. To avoid this issue and efficiently conduct aging research, the National Center for Geriatrics and Gerontology operates its "Aging Farm", a system that supplies aged animals in response to researchers' requests. In the present study, as part of the Aging Farm project, we examined changes in the physiological functions of the lungs and gene expression in lung tissues of Aging Farm animals as they aged. A decline in the physiological function of the lungs was already apparent before 6 months of age, and it continued until at least 1 year of age. On the other hand, gene expression profiling by RNA sequencing showed small changes in the early stages of aging but more pronounced changes at 12 and 24 months of age than at 3 months of age. Age-related lung tissue changes are considered to be involved in the pathogenesis of various chronic respiratory diseases, and the characterization of animals as they age will ensure the quality of the Aging Farm as a resource for aging research.

МОРФОЛОГІЧНА ОЦІНКА ПОШКОДЖЕННЯ ЛЕГЕНЬ У МОЛОДИХ ЩУРІВ, ВИКЛИКАНЕ ЧАСТКОВОЮ ОКЛЮЗІЄЮ ТРАХЕЇ

A decrease in the lumen of the upper respiratory tract (the trachea) in newborn infants is the main cause of impaired development of lungs during postnatal ontogenesis. Aim. To study the histological changes in the lung tissue of young sexually immature animals when modeling partial tracheal stenosis. Materials and methods. Young male Wistar rats aged 25-28 days and weighing 42-54 g were divided into 4 groups: 1) control (intact); 2) animals with tracheal stenosis (7 days); 3) animals with tracheal stenosis (21 days); 4) animals with tracheal stenosis (7 days after surgery followed by observation for 2 weeks). Modeling of stenosis was reproduced by applying a ligature at the level of the upper quarter of the trachea. This caused a narrowing of the tracheal lumen by 25-30%. The histological changes of the lungs in animals of all experimental groups were studied. Results. A significant structural damage to the alveoli and swelling of the alveolar acini were revealed on the 7th day of the development of tracheal stenosis. A partial reduction of pathomorphological changes was observed on day 21. The removal of the ligature from the trachea was accompanied by a gradual restoration of the normal histological structure of the animal lung tissue, while maintaining individual zones of hypoxic damage. At the same time, intra-alveolar edema, wedening of the alveolar lumen, a decrease in the thickness of their walls, structural disorders of the alveolar-capillary membrane, the accumulation of hemorrhagic contents, and destructive changes in the cells of the pulmonary acini were observed in the lung tissue. Long-term hypoxia (21 days) was accompanied by a partial regression of these damages with a simultaneous increase in the number of macrophages and massive death of pulmonary acini cells. In group 4 animals, after removing the ligature, in addition to the trachea damage the preservation of separate dystrophic changes was observed. Conclusions. In tracheal stenosis model and acute hypoxic-respiratory hypoxia, dystrophic changes in the lung tissue were revealed. With an increase in the duration of hypoxic exposure, a gradual adaptation of the cellular elements and metabolic processes to the conditions of impaired oxygenation was observed. Restoration of lung ventilation accelerates the development of compensatory and regenerative processes in lung cells against the background of the preservation of pronounced structural and morphological disorders. Keywords: hypoxia, lungs, tracheal stenosis, histological changes, acini.

Application of Precision-Cut Lung Slices as an In Vitro Model for Research of Inflammatory Respiratory Diseases.

The leading cause of many respiratory diseases is an ongoing and progressive inflammatory response. Traditionally, inflammatory lung diseases were studied primarily through animal models, cell cultures, and organoids. These technologies have certain limitations, despite their great contributions to the study of respiratory diseases. Precision-cut lung slices (PCLS) are thin, uniform tissue slices made from human or animal lung tissue and are widely used extensively both nationally and internationally as an in vitro organotypic model. Human lung slices bridge the gap between in vivo and in vitro models, and they can replicate the living lung environment well while preserving the lungs' basic structures, such as their primitive cells and trachea. However, there is no perfect model that can completely replace the structure of the human lung, and there is still a long way to go in the research of lung slice technology. This review details and analyzes the strengths and weaknesses of precision lung slices as an in vitro model for exploring respiratory diseases associated with inflammation, as well as recent advances in this field.

Benzo(A)Pyrene-Induced Lung Cancer: Chemo Protective Effect of Coronarin D in Swiss Albino Mice.

Lung cancer is considered one of the most prevalent cancers worldwide and also has a high death rate. The prevalence of lung cancer is high in developed countries than in developing countries due to the lifestyle changes and quality of air. Coronarin D is a diterpene, which is isolated from the Hedychium coronarium. It demonstrated several pharmacological properties such as anti-allergic, anti-inflammatory, antimicrobial, and anticancer activities. In the current investigation, the potential of Coronarin D on the B(a)P-induced lung cancer was studied in the experimental mice model. The B(a)P-administrated animals exhibited a reduced level of immune cells, IgG, IgM, immune complexes, SOD, and CAT. The B(a)P-administrated animals expressed high levels of IgA, LPO, xenobiotic markers, tissue marker, tumor marker, and proinflammatory cytokines. On treatment with Coronarin D, the level of neutrophils, lymphocytes, leucocytes, and absolute neutrophils was elevated in the B(a)P-administered mice. The immune complex was augmented in the Coronarin D-treated animals in comparison with B(a)P-treated mice. The level of IgG and IgM was increased, whereas the level of IgA was reduced in the Coronarin D-treated animals. The level of LPO was downregulated, whereas the level of SOD and CAT was upregulated in Coronarin D-treated animals. The expression level of xenobiotic markers, tissue marker, tumor marker, and proinflammatory cytokines was reduced in the Coronarin D-treated animals. The histopathological results revealed that lung tissues of Coronarin D-treated animals had less alveolar damage with decreased hyperplasia. These findings suggest that the Coronarin D can be utilized as a potent chemopreventive agent for treating lung cancer in the future.

Involvement of Cu-containing amine oxidases in the development of lung pathology in ovalbumin-induced bronchial asthma in guinea pigs

Bronchial asthma is developed as an immune response to allergen challenges accompanied by inflammation and fibrosis implicated in airway remodeling. To reveal the causative implication of Cu-containing amino oxidases semicarbazide-sensitive amine oxidase (SSAO), DAO and lysyl oxidase (LOX) in BA development we used their irreversible inhibitor semicarbazide and guinea pig model of BA induced by ovalbumin. Semicarbazide was introduced to asthmatic animals via drink or inhalation. At the 16th week after disease induction, the increase in the activity of pro-inflammatory SSAO and DAO in plasma (1.6 and 2 times, respectively) was observed. The introduction of semicarbazide to asthmatic animals via drink or inhalation significantly decreased activities of these enzymes compared to the untreated asthmatic animals. A considerable­ increase in IL-13 content and LOX activity in the lung tissue of asthmatic animals were observed that evidenced airway inflammation and pulmonary fibrosis development. The uptake of semicarbazide by guinea pigs with bronchial asthma led to normalization of LOX activity. Histological studies confirmed that semicarbazide attenuated morphopathological changes in the lungs of asthmatic animals. Thus, the data obtained indicate the direct participation of the studied enzymes in the progression of pathological processes in atopic bronchial asthma as well as the potential use of semicarbazide as a drug in complex anti-asthmatic therapy. Keywords: atopic bronchial asthma, histaminase/diamine oxidase, IL-13, lysyl oxidase, nitric oxide, semicarbazide, semicarbazide sensitive amine oxidase

Size characteristics of asbestiform fibers in lung tissue of animals that grazed in areas rich in ophiolitic outcrops in Central Calabria (Southern Italy)

In Calabria (Southern Italy) naturally occurring asbestos (NOA) mainly occurs in the ophiolitic sequences cropping in the Mount Reventino area. The most common type of asbestos detected was the amphibole tremolite; fibrous antigorite and minor chrysotile were also found. The development of asbestos-related diseases depends on, among other things, the morphological characteristics of fibers, length and width, affecting the durability of asbestos fibers in the lung.In this work fifteen lung samples of sheep, goats and wild boars, grazing around the Mount Reventino area were collected and asbestos fibers analysed. Observed fibers (357), of which 97 % were tremolite and 3 % antigorite fibers, were grouped according to species, grazing area and age of the animals. The aim of this work was to highlight any differences among the groupings and to compare our size results with data in literature related to exposed populations.Principal Component Analysis (PCA) highlighted a positive correlation between tremolite fiber length and width and revealed groupings in terms of animal age. The Kruskal-Wallis test showed statistically significant differences between fiber mean widths in young and old animals. 63 % observed asbestiform fibers were longer than 5 μm and 7 % of the fibers were longer than 20 μm (critical fiber length connected to the frustrated phagocytosis by the macrophage). Fibers conforming to the Stanton Hypothesis size (predictor of the carcinogenic potency of fibers) were 1 %.Our size parameters of fibers detected in the animal lungs were in fairly good agreement with literature data for human asbestos exposure to tremolite.These results confirmed that an animal-sentinel system could be used to monitor the natural background of the airborne breathable fibers exposure. In addition, the size correlation of animal-human breathed fibers could be useful to study their potential toxicity.Additional data are necessary for improving the agreement with human exposure data.

Regulation of PARP-1 deficiency on epidermal growth factor receptor during lung injury of mice induced by benzo [a] pyrene inhalation exposure

To investigate the regulation of PARP-1 deficiency on epidermal growth factor receptor(EGFR) during lung injury of mice induced by benzo[a]pyrene(B[a]P) inhalation exposure. PARP-1 knockout mice(PARP-1~(-/-)) and WT mice were selected as the object, and which were randomly assigned into either an intervention or a control group(n=40, half male and half female). The intervention group were individually treated with 10.0 μg/m~(3 )B[a]P for 180 days by dynamic inhalation exposure(6 h per day and 5 days per week), and the control group was given the solvent dimethyl sulfoxide(DMSO) during the same period. The expression of EGFR in lung tissues of animals were examined by RT-PCR, Western blot and immunofluorescence. In WT mice, the intervention manifested significant increase expression of EGFR in lung tissue, but no changes were found in the control. In PARP-1~(-/-) mice, the intervention manifested significant inhibition expression of EGFR, but the control group exhibited no changes. PARP-1 deficiency suppresses the abnormal activation of EGFR during lung injury of mice induced by B[a]P inhalation exposure.