Morphological Changes In Lungs Research Articles

Long-term pulmonary repair in rat lungs after sublobar resection: electrocautery versus stapler methods.

We investigated and compared the long-term (6-month) histologic changes in a rat model of sublobar resection created using electrocautery or stapler techniques. Nine-week-old male rats were anesthetized and intubated; thoracotomy with sublobar resection was performed in the right middle lobe using electrocautery or stapler techniques. Histological examination was performed at 2, 4, 8, 12, and 24weeks post-surgery to assess long-term effects on lung tissue repair and morphologic changes. Lung expansion and alveolar epithelial cell proliferation were evaluated by measuring the mean linear intercept and counting the number of alveolar type I and II cells. The electrocautery group showed signs of lung self-repair at the resected area over time, with inflammatory cell infiltration followed by growth of vessels and bronchioles. Mesothelial cells covered the resected area by 2weeks; elastic fibers gradually connected from both sides by 24weeks. Lung expansion, measured by mean linear intercept, was initially small below the electrocautery resection area at 2weeks but recovered from 4 to 24weeks. The stapler group showed persistently small mean linear intercept over time. In the electrocautery group, the number of alveolar type II cells was higher just below the resection than in other areas from 2 to 24weeks, followed by alveolar type I cells (4 to 24weeks). The stapler group showed a transient alveolar type II cell increase at 2weeks. Compared to the stapler technique, electrocautery mayprovide advantages for postoperative lung repair by promoting lung expansion and alveolar epithelial cell proliferation.

Longitudinal Magnetic Resonance Imaging of Changes in Lung Morphology and Perfusion in Children with Cystic Fibrosis From Infancy through Adolescence.

The progression of lung changes in cystic fibrosis (CF) from infancy through adolescence remains poorly understood due to limited longitudinal imaging data. To assess changes in lung morphology and perfusion in children with CF through the pediatric age range by longitudinal chest magnetic resonance imaging (MRI). 1112 annual chest MRI were performed in 226 patients with CF aged 0-18yr. MRI was assessed using a validated MRI scoring system. The MRI global score continuously increased from 5.5±4.6 at infancy (0yr) to 17.9±8.4 at adolescence (range 12-18yr), and the MRI morphology score from 5.0±3.9 to 12.4±6.0 (P<0.001). Bronchiectasis/wall thickening prevalence increased from 89.1% at infancy to approx. 100% from preschool age (1-5yr), and the subscore increased from 3.1±1.9 at infancy to 6.6±2.1 at adolescence (P<0.001). Mucus plugging prevalence increased from 55.4% at infancy to 83.5% at adolescence, and the subscore increased from 1.2±1.6 to 3.7±2.5 in the same period (P<0.001). Perfusion abnormalities were found in 44.4% at infancy, and increased to approx. 90% from preschool age (P<0.001). The MRI perfusion score increased from 1.1±1.6 at infancy to 5.6±3.0 at adolescence (P<0.001). Chronic Pseudomonas aeruginosa infection was associated with higher MRI scores from school age (6-11yr, P<0.05-0.001). This is the first study assessing longitudinal changes in lung morphology and perfusion in CF throughout the pediatric age range, providing percentiles as age-specific reference for lung disease severity. Our data may facilitate the use of MRI as an endpoint in clinical trials in children with CF.

Protective Role of Quercetin on Carmustine-induced Lung Toxicity in Adult Male Albino Rats

Background: Carmustine (BCNU) is an alkylating agent used as an antineoplastic agent. A major problem with the clinical use of BCNU is the occurrence of pulmonary toxicity. Quercetin (QUE) is an important polyphenolic flavonoid that exhibits antioxidant, anti-inflammatory and other health-promoting effects. This study aimed to investigate the protective effect of QUE on BCNU-induced lung injury in rats using histologic and biochemical methods. Methods: Forty adult male albino rats were divided into 4 groups: Group I served as the control group. Group ІІ received QUE orally in a dose of 100 mg/kg per day for 7 days. Group ІІI received a single dose (30 mg/kg) of BCNU intraperitoneally (i.p.) on the 7th day of the study. Group ІV received (BCNU + QUE). On the 8th day of the experiment, lung tissues were collected for histopathological examinations. The levels of malondialdehyde (MDA), hydroxyproline (HYP), myeloperoxidase (MPO), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) were also determined in all dissected tissues. Results: Pretreatment with QUE ameliorated lung morphological changes noticed in the BCNU group and the levels of MDA, HYP, and MPO were significantly decreased whereas those of GSH, GSH-Px, and SOD were significantly increased. Conclusions: QUE provides a protective effect against BCNU-induced lung injury by reducing oxidative stress and pulmonary fibrosis.

High resolution fluorescence imaging of the alveolar scaffold as a novel tool to assess lung injury

Acute lung injury (ALI) represents an aetiologically diverse form of pulmonary damage. Part of the assessment and diagnosis of ALI depends on skilled observer-based scoring of brightfield microscopy tissue sections. Although this readout is sufficient to determine gross alterations in tissue structure, its categorical scores lack the sensitivity to describe more subtle changes in lung morphology. To generate a more sensitive readout of alveolar perturbation we carried out high resolution immunofluorescence imaging on 200 μm lung vibratome sections from baseline and acutely injured porcine lung tissue, stained with a tomato lectin, Lycopersicon Esculentum Dylight-488. With the ability to resolve individual alveoli along with their inner and outer wall we generated continuous readouts of alveolar wall thickness and circularity. From 212 alveoli traced from 10 baseline lung samples we established normal distributions for alveolar wall thickness (27.37; 95% CI [26.48:28.26]) and circularity (0.8609; 95% CI [0.8482:0.8667]) in healthy tissue. Compared to acutely injured lung tissue baseline tissue exhibited a significantly lower wall thickness (26.86 ± 0.4998 vs 50.55 ± 4.468; p = 0.0003) and higher degree of circularityϕ≤ (0.8783 ± 0.01965 vs 0.4133 ± 0.04366; p < 0.0001). These two components were subsequently combined into a single more sensitive variable, termed the morphological quotient (MQ), which exhibited a significant negative correlation (R2 = 0.9919, p < 0.0001) with the gold standard of observer-based scoring. Through the utilisation of advanced light imaging we show it is possible to generate sensitive continuous datasets describing fundamental morphological changes that arise in acute lung injury. These data represent valuable new analytical tools that can be used to precisely benchmark changes in alveolar morphology both in disease/injury as well as in response to treatment/therapy.

Histopathological Analysis of Lung Lesions in Cases of Sudden Death: An Autopsy-based Study

Introduction: Cardiovascular and respiratory causes account for the major chunks in sudden death cases in various Western studies. Overall, a very limited number of studies have been conducted on respiratory system changes in cases investigated as sudden and unknown death in India. Pathological respiratory findings are said to be common in the autopsy population; however, their nature and prevalence are not well documented. Aim: To document the morphologic changes in lungs (both gross and microscopic) in cases of sudden death. Materials and Methods: The present study was a cross- sectional, prospective, and observational study conducted over a period of 12 months from 1st April 2010 to 31st March 2011. It was conducted on autopsy lung specimens received in the Department of Pathology, RG Kar Medical College and Hospital, Kolkata, West Bengal, India. For the purpose of present study, sudden death was defined as death occurring within 24 hours of the onset of the terminal symptoms. Unidentified subjects who were declared “Brought Dead” at the emergency room were also included in the study. The lungs were fixed in 10% formalin, weighed, and dimensions measured. Grossly, the lungs were examined for colour, volume, consistency, presence of any pathological changes, the status of bronchi and pleura, and findings were recorded. After routine processing and paraffin embedding, histological sections were stained with Haematoxylin and Eosin (H&amp;E) stain and special stains as and when necessary. All the histological sections were examined microscopically, and findings were recorded. The obtained data were subjected to appropriate statistical analysis by entering the data in Microsoft (MS) excel 2010. Results: There were 46 males (88.46%) and 6 females (11.54%). The age range was 26-86 years, with a mean age of 51.02 years. Among the 52 cases, significant pulmonary pathology was found in 26 cases (50%), excluding postmortem changes. Extensive fibrocaseous pulmonary Tuberculosis (TB) 15 (28.85%) was the most common pulmonary lesion found, present in all age groups. The other major pathological lesions encountered were lobar pneumonia 4 (7.69%), emphysema 3 (5.77%), bronchopneumonia 2 (3.85%), etc. Conclusion: A significant number of cases with pathological lesions in the lung were detected during the histopathological examination of sudden death cases. All the lesions may or may not have contributed to death in a direct or indirect way. The undetected lung pathologies emphasise the importance of autopsy in cases of sudden death.

Effects of the ACE2-Ang-(1-7)-Mas axis on gut flora diversity and intestinal metabolites in SuHx mice.

Pulmonary artery hypertension (PAH) poses a significant challenge due to its limited therapeutic options and high mortality rates. The ACE2-Ang-(1-7)-Mas axis plays a pivotal role in regulating blood pressure and inhibiting myocardial remodeling. However, the precise mechanistic links between the ACE2-Ang-(1-7)-Mas axis and PAH remain poorly understood. This study aimed to elucidate the involvement of the ACE2-Ang-(1-7)-Mas axis in the development of PAH. PAH was induced in mice using Sugen5416/hypoxia, PAAT/PET ratio and PA were detected using cardiac ultrasound; inflammation related factors such as MCP-1, TNF, IL-10and IL-12p70 were detected in intestines using cytometric bead array (CBA) kits; histopathological and morphological changes in lung and intestinal tissues were assessed via HE staining and Masson staining to evaluate the progression of PAH. Immunohistochemistry and western blotting were employed to determine the expression levels of two tight junction proteins, occludin and ZO-1, in intestinal tissues. Additionally, 16rRNA sequencing and non-targeted metabolomics by LC-MS/MS techniques were utilized to investigate the impact of the ACE2-Ang-(1-7)-Mas axis on microbial diversity and metabolomics of intestinal contents. Activation of the ACE2-Ang-(1-7)-Mas axis improves heart function, reduces intestines inflammatory factors and ameliorates pathological and histological alterations in SuHx mice. This activation notably upregulated the expression of occludin and ZO-1 proteins in intestinal tissues and promoted the proliferation of SCFA-producing bacteria genera, such as g_Candidatus_Saccharimonas. Furthermore, it enhanced the abundance of beneficial metabolites, including tryptophan and butyric acid. The findings suggest that modulation of the ACE2-Ang-(1-7)-Mas axis can alleviate PAH by regulating intestinal microbes and metabolites. These results highlight the potential of the ACE2-Ang-(1-7)-Mas axis as a promising therapeutic target for clinical management of PAH.

Probe-based confocal laser endomicroscopy for evaluating high-altitude pulmonary edema in canines

BackgroundReal-time assessment of high-altitude pulmonary edema (HAPE) remains a challenge. Probe-based confocal laser microscopy (pCLE) allows a real-time in vivo visualization of the alveoli. This study aimed to develop a new non-invasive method for analyzing microscopic images in a canine model of HAPE using pCLE. Materials and methodsThis was a prospective, controlled animal study in adult male beagle dogs randomized to control and HAPE groups. The HAPE group was exposed to a high altitude of 6000 m for 48 h. The blood gas levels, lung morphological changes, infectious factors, and lung wet-to-dry ratio were analyzed in different groups. The pCLE images were described based on the volume air index (VAI), which applies an integral over specific signal intensities. ResultsThe lung wet-to-dry weight ratio and injury scores in the HAPE group were significantly increased compared with those of the control group. The levels of infectious factors interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6 were significantly increased in the HAPE group compared with those in the control group. VAI was significantly decreased in the HAPE group. ConclusionpCLE is a potential adjudicative bronchoscopic imaging technique for assessing HAPE. VAI may be acquired from quantitative parameters in the analysis of images.

Evidence for Wnt signaling’s central involvement in perinatal nicotine exposure-induced offspring lung pathology and its modulation by electroacupuncture

ObjectiveMany factors during pregnancy can induce intrauterine growth restriction (IUGR), resulting in various adverse perinatal outcomes such as low birth weight and multiple organ disorders. Among these factors, prenatal smoke/nicotine exposure is a common cause of IUGR, often associated with altered fetal lung development. The classical Wnt signaling pathway plays a vital role in lung development, and its alterations are commonly associated with developmental lung pathologies. The purpose of this study was to determine whether electroacupuncture (EA) at "Zusanli" (ST 36) points protects perinatal nicotine exposure (PNE)-induced offspring lung dysplasia through Wnt/β-catenin signaling pathway and to identify specific Wnt signaling pathway targets of EA. MethodsFollowing a well-established protocol, nicotine (1 mg/kg/ body weight) was administered subcutaneously to pregnant Sprague Dawley rat dams from gestational day 6 to postnatal day 21. In the EA group, dams were treated with EA at both ST 36 acupoints, while in another experimental group, Wnt/β-catenin signaling pathway agonist was injected subcutaneously (2 mg/kg/ body weight). Offspring body weight (PND 1, 7, 14, and 21), lung weight, Wnt signaling markers, pulmonary function, and lung morphology were determined at sacrifice on PND 21. Specifically, Western blotting and Real-time PCR were used to detect the protein and mRNA levels of critical Wnt signaling markers Wnt2, Wnt7b, FZD4, FZD7, LRP5, and LRP6 in the offspring lung. The protein levels of β-catenin in lung tissue of offspring rats were detected by ELISA that of LEF-1 by Western blotting. ResultsCompared to the control group, the body and lung weights of the offspring rats were significantly decreased in the nicotine-only exposed group. The pulmonary function determined as FVC, PEF, TV, and Cdyn was also significantly decreased, while PIF was significantly increased. The protein levels and mRNA expression of Wnt2, Wnt7b, FZD4, FZD7, LRP5, and LRP6 in the lung tissue of the PNE offspring rats were significantly increased. With EA administration at ST 36 acupoints concomitant with nicotine administration, the body and lung weights, pulmonary function (FVC, PEF, PIF, TV, and Cdyn), protein and mRNA levels Wnt signaling pathway markers (Wnt2, Wnt7b, FZD4, FZD7, LRP5, LRP6, β-catenin, and LEF-1) normalized and were not different from the control group. Notably, Wnt agonists agonist administration blocked the protective effects of EA against PNE-induced lung morphological, molecular, and function changes, highlighting the central significance of Wnt pathway signaling in PNE-induced offspring pulmonary pathology and its modulation by EA at ST 36 acupoints. ConclusionConcomitant maternal EA at ST 36 acupoints from gestational day 6 to PND 21 protects against offspring PNE-induced lung phenotype. The protective effect is achieved by regulating the expression of Wnt ligand proteins (Wnt2 and Wnt7b) and receptor proteins (FZD4, FZD7, LRP5, and LRP6) upstream of the Wnt/β-catenin signaling pathway intermediates β-catenin, and LEF-1.

Structural changes in lung morphology detected by MRI after modulating therapy with elexacaftor/tezacaftor/ivacaftor in adolescent and adult patients with cystic fibrosis

IntroductionElexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) improves CFTR function in cystic fibrosis (CF) patients homozygous or heterozygous for F508del mutation. The aim of the study was to evaluate the response to ELX/TEZ/IVA treatment both clinically and morphologically in terms of bronchiectasis, bronchial wall thickening, mucus plugging, abscess and consolidations. MethodsWe retrospectively collected data from CF patients followed at Parma CF Centre (Italy) treated by ELX/TEZ/IVA between March and November 2021. Post-treatment changes in respiratory function, quality of life, sweat chloride concentration, body mass index, pulmonary exacerbations and lung structure by chest magnetic resonance imaging (MRI) were assessed. T2-and T1-weighted sequences were acquired with a 20 min-long scanning protocol on a 1.5T MRI scanner (Philips Ingenia) without administration of intravenous contrast media. Results19 patients (32.5 ± 10.2 years) were included in the study. After 6 months of treatment with ELX/TEZ/IVA, MRI showed significant improvements in the morphological score (p < 0.001), with a reduction in bronchial wall thickening (p < 0.001) and mucus plugging (p 0.01). Respiratory function showed significant improvement in predicted FEV1% (58.5 ± 17.5 vs 71.4 ± 20.1, p < 0.001), FVC% (79.0 ± 11.1 vs 88.3 ± 14.4, p < 0.001), FEV1/FVC (0.61 ± 0.16 vs 0.67 ± 0.15, <0.001) and LCI2.5% (17.8 ± 4.3 vs 15.8 ± 4.1 p < 0.005). Significant improvement was found in body mass index (20.6 ± 2.7 vs 21.9 ± 2.4, p < 0.001), pulmonary exacerbations (2.3 ± 1.3 vs 1.4 ± 1.3 p 0.018) and sweat chloride concentration (96.5 ± 36.6 vs 41.1 ± 16.9, p < 0.001). ConclusionsOur study confirms the efficacy of ELX/TEZ/IVA in CF patients not only from a clinical point of view but also in terms of morphological changes of the lungs.

A multiple comorbidities mouse lung infection model in ApoE‑deficient mice.

Acute pneumonia is characterised by a period of intense inflammation. Inflammation is now considered to be a key step in atherosclerosis progression. In addition, pre-existing atherosclerotic inflammation is considered to play a role in pneumonia progression and risk. In the present study, a multiple comorbidities murine model was used to study respiratory and systemic inflammation that results from pneumonia in the setting of atherosclerosis. Firstly, a minimal infectious dose of Streptococcus pneumoniae (TIGR4 strain) to produce clinical pneumonia with a low mortality rate (20%) was established. C57Bl/6 ApoE -/- mice were fed a high-fat diet prior to administering intranasally 105 colony forming units of TIGR4 or phosphate-buffered saline (PBS). At days 2, 7 and 28 post inoculation (PI), the lungs of mice were imaged by magnetic resonance imaging (MRI) and positron emission tomography (PET). Mice were euthanised and investigated for changes in lung morphology and changes in systemic inflammation using ELISA, Luminex assay and real-time PCR. TIGR4-inoculated mice presented with varying degrees of lung infiltrate, pleural effusion and consolidation on MRI at all time points up to 28 days PI. Moreover, PET scans identified significantly higher FDG uptake in the lungs of TIGR4-inoculated mice up to 28 days PI. The majority (90%) TIGR4-inoculated mice developed pneumococcal-specific IgG antibody response at 28 days PI. Consistent with these observations, TIGR4-inoculated mice displayed significantly increased inflammatory gene expression [interleukin (IL)-1β and IL-6] in the lungs and significantly increased levels of circulating inflammatory protein (CCL3) at 7 and 28 days PI respectively. The mouse model developed by the authors presents a discovery tool to understand the link between inflammation related to acute infection such as pneumonia and increased risk of cardiovascular disease observed in humans.

β-Sitosterol inhibits ovalbumin-induced asthma-related inflammation by regulating dendritic cells

Aim To investigate the effects of β-sitosterol (B-SIT) and the underlying mechanisms of action in an ovalbumin-induced rat model of asthma. Methods The pathological and morphological changes in lung and tracheal tissues were observed by H&E, PAS, and Masson’s staining. The levels of IgE, TNF-α, and IFN-γ in the bronchoalveolar lavage fluid (BALF) and those of IL-6, TGF-β1, and IL-10 in serum were measured by ELISA. The relative expression levels of IL-5, IL-13, IL-21, CD11c, CD80, and CD86 mRNA in lung tissue were examined by RT-qPCR. Flow cytometry was performed to assess the levels of immune cells, including macrophages and neutrophils in spleen tissue and Th cells, Tc cells, NK cells, and DCs in peripheral blood. The protein expression levels of CD68, MPO, CD11c, CD80, and CD86 were detected by western blotting or immunohistochemistry. Results B-SIT improved the injury in OVA-induced pathology, decreased the levels of inflammatory factors of IgE, TNF-α, IL-6, TGF-β1, IL-5, IL-13, and IL-21 and increased the levels of IFN-γ and IL-10. In addition, B-SIT decreased the number of macrophages and neutrophils and the relative expression levels of CD68 and MPO in the spleen. Moreover, B-SIT increased the number of Th cells, Tc cells, NK cells, and DCs in peripheral blood and upregulated the levels of CD11c, CD80, and CD86 in the spleen and lung. Conclusion B-SIT improved symptoms in a rat model of asthma likely via the inhibition of inflammation by regulating dendritic cells.

Pathologic Changes in Lung Morphology in Experimental Klebsiella pneumoniae and Trypanosoma brucei co-Infection in West African Dwarf

The bacteria Klebsiella pneumoniae easily takes advantage of compromised immune status to induce pathologies on their hosts. This study investigated pulmonary pathomorphologies associated with experimental co-infection of Klebsiella pneumoniae and Trypanosoma brucei in West African Dwarf goats. Fifteen clinically healthy male goats of about six months of age were used in this study. They were randomly assigned into five groups of three each. Group I was the uninfected/negative control; Group II was infected with K. pneumoniae only as positive control I; Group III with T. brucei followed by acute K. pneumoniae infection at day 7 post T. brucei infection; Group IV with T. brucei followed by sub-acute K. pneumoniae at day 14 post T. brucei and Group V with T. brucei only, as positive control II. Throughout the study period, K. pneumoniae was only re-isolated from goats in Grp IV. Grossly, no lesions were observed in the lungs of goats in Grp II, while lungs of goats in Grp III showed mild consolidation in the cardiac lobes. Lungs of Grp IV goats showed multifocal abscessation and red hepatisation, and Grp V had widespread hyperaemia in all lobes. The histology showed mild intra-alveolar exudations and alveolar collapse in Grp II, mild to moderate cellular infiltrations and sero-fibrinous exudations in Grp III, and severe bronchopneumonia with fibrino-purulent exudations in Grp IV. Grp V had generalised oedema and hyperaemia. This study has shown that Trypanosoma brucei immunosuppresses infected goats, making them vulnerable to pneumopathies from Klebsiella pneumoniae.

Ischemic preconditioning does not prevent placental dysfunction induced by fetal cardiac bypass.

Remote ischemic preconditioning (rIPC) has been applied to attenuate tissue injury. We tested the hypothesis that rIPC applied to fetal lambs undergoing cardiac bypass (CB) reduces fetal systemic inflammation and placental dysfunction. Eighteen fetal lambs were divided into three groups: sham, CB control, and CB rIPC. CB rIPC fetuses had a hindlimb tourniquet applied to occlude blood flow for four cycles of a 5-minperiod, followed by a 2-minreperfusion period. Both study groups underwent 30 min of normothermic CB. Fetal inflammatory markers, gas exchange, and placental and fetal lung morphological changes were assessed. The CB rIPC group achieved higher bypass flow rates (p < .001). After CB start, both study groups developed significant decreases in PaO2 , mixed acidosis, and increased lactate levels (p < .0004). No significant differences in tissular edema were observed on fetal lungs and placenta (p > .391). Expression of Toll-like receptor 4 and intercellular adhesion molecule-1in the placenta and fetal lungs did not differ among the three groups, as well as with vascular cell adhesion molecule-1(VCAM-1) of fetal lungs (p > .225). Placental VCAM-1 expression was lower in the rIPC group (p < .05). Fetal interleukin-1 (IL-1) and thromboxane A2 (TXA2) levels were lower at 60 min post-CB in the CB rIPC group (p < .05). There were no significant differences in tumor necrosis factor-α, prostaglandin E2, IL-6, and IL-10 plasma levels of the three groups at 60-minpost-bypass (p > .133). Although rIPC allowed increased blood flow during fetal CB and decreasedIL-1 and TXA2 levels and placental VCAM-1, it did not prevent placental dysfunction in fetal lambs undergoing CB.

Клинико-морфологические особенности немелкоклеточного рака легкого у больных с разными вариантами гистологических изменений бронхиального эпителия

Lung cancer occupies the leading position in the global structure of oncological diseases. Despite significant advances in its treatment, the survival remains low. Morphological changes to the bronchial epithelium outside the tumor may provide important cues on progression of the disease in patients with lung cancer. This study aimed to identify associations between morphological and clinical features of non-small cell lung cancer and morphological changes to the epithelium in small bronchi outside the tumor. The study encompassed tumor specimens collected from 90 patients, 75 (83%) men and 15 (17%) women, diagnosed with non-small cell lung cancer. The average age of the patients was 67.8 ± 7.4 years. The results indicate higher frequency of lymphogenous metastasis in patients with combined basal cell hyperplasia and squamous metaplasia (BCH+SM+ group) compared to patients with isolated basal cell hyperplasia (BCH+SM– group, p = 0.05). The BCH+SM– group presented with higher rates of hematogenous metastasis compared to BCH+SM+ and BCH–SM– groups (p = 0.004 and p = 0.0019, respectively), as well as increased representation of low-differentiated structures in the primary tumors. The results suggest a commonality of parenchymal-stromal interactions in non-small cell lung cancers and their surroundings and a significant impact of these interactions on differentiation status and progression of the tumors.

The protective effect of \u03b2-cryptoxanthin against cyclophosphamide-induced lung injury in adult male albino rats

BackgroundCyclophosphamide (CYP) is an anticancer agent widely used in chemotherapy. It has been suggested that CYP causes toxicity in many organs, including the lungs and testes. Many studies have indicated that some antioxidants have possible protective effects against CYP’s side effects. β-cryptoxanthin (BCX), a major carotenoid of potential interest for health, is known for its antioxidant activities. This study aimed to investigate the protective effect of BCX on CYP-induced lung injury in rats using histologic and biochemical methods.MethodsForty adult male albino rats were divided into 4 groups: Group I served as the control group. Group II received BCX orally in a dose of 4 mg/kg per day for 7 days. Group III received a single dose (200 mg/kg) of CYP intraperitoneally (i.p.) on the 7th day of the study. Group IV received (CYP + BCX). On the 8th day of the experiment, lung tissues were collected for histopathological examinations. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), reduced glutathione (GSH), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were also determined in all dissected tissues.ResultsPretreatment with BCX ameliorated lung morphological changes noticed in CYP group and the levels of MDA and MPO were significantly decreased whereas those of GSH, GSH-Px and SOD were significantly increased.ConclusionsBCX provides a protective effect against CYP-induced lung injury by reducing oxidative stress and pulmonary fibrosis.

Mechanistic insights into the amelioration effects of lipopolysaccharide-induced acute lung injury by baicalein: An integrated systems pharmacology study and experimental validation

BackgroundAcute lung injury is an acute progressive respiratory failure caused by several of non-cardiogenic factors which involves in excessive amplification or uncontrolled inflammatory response. ObjectivesIn this study, we investigated the protective effect of baicalein against acute lung injury induced by LPS and explored the underlying mechanisms. MethodsForty-eight SPF male C57BL/6 mice were randomly divided into normal group, model group, dexamethasone group and baicalein low-dose, medium-dose and high-dose groups. After 5 days of adaptive feeding, the mice were intraperitoneally injected with LPS and dissected after 12 h. Hematoxylin-eosin staining, ELISA assay, immunofluorescence assay and Western-Blot were applied to appraise microstructural changes and protein expressions of lung tissues. Systems pharmacology study was used to evaluate the protection of baicalein on acute lung injury. FindingsThe results showed that baicalein administration could significantly inhibit LPS-induced lung morphological changes, inhibit inflammatory response and pyroptosis. A total of forty-three potential targets of baicalein and acute lung injury were obtained. And PI3K-Akt, TNF and NF-κB were mainly signaling pathways. It is worth mentioning that this experiment also confirmed that NLRP3, caspase-1 and other inflammasome are involved in pyroptosis. ConclusionBaicalein has protected against LPS-induced lung tissues injury via inhibiting inflammatory response and pyroptosis.

Патоморфологические изменения некоторых органов и тканей в периоде реконвалесценции коронавирусной инфекции COVID-19

New coronavirus infection (COVID-19) is highly contagious viral disease caused by SARS-CoV-2 leading to the pandemic. The autopsy of COVID-19 patients often showed features of previous brain diseases including neurodegeneration, previous strokes, demyelinating diseases and atherosclerosis. Patients with acute cerebrovascular accidents and severe COVID-19 had higher numbers of lethality in comparison to non-severe course of infection without cerebrovascular accidents. A comparative analysis of morphological changes in lungs of deceased patients who died in different periods of first clinical symptoms is to be conducted. Objective. Description of pathomorphological changes in deceased patients during the period of reconvalescence. Patients and methods. The analysis of 15 fatal cases which took place in Botkin Hospital with the diagnosis of ischemic stroke and new coronavirus infection in the previous 2-4 months has been held. Macro and microscope examination of brain, lungs, brachiocephalic arteries, kidneys and liver has been carried out. Results. All patients had morphological features of ischemic damage of grey matter in the brain. Beside necrosis of neurocytes with diffuse infiltration in the grey matter, hematoxylin cycles were found, in some cases they were placed in a perivascular way in choroid plexus. Also 5 patients suffered a myocardial infarction up to 3 days. 10 patients had structures disorganisation in areas of lung parenchyma with hystoacrchitectonic changes because of the fibrosis. Alveoli in some places collaborated mostly with single airway clearance. The fact that most patients had lung hemosiderosis can prove coronavirus infection suffered earlier with microcirculatory bed damage. Conclusion. Thus, morphological changes seen in the period of reconvalescence of COVID-19 is a result of pathomorphosis of changes described earlier for acute period of coronavirus infection and affect not only lungs, but also other organs and tissues. This proves systematic characteristic of the infection. Key words: COVID-19, acute cerebrovascular accidents, stroke, pathomorphological changes in the brain

КОМП’ЮТЕРНА ТОМОГРАФІЧНА ДЕНСИТОМЕТРІЯ ЛЕГЕНЬ В АЛГОРИТМІ ДІАГНОСТИКИ ІНТЕРСТИЦІАЛЬНИХ ЗАХВОРЮВАНЬ ЛЕГЕНЬ, В ТОМУ ЧИСЛІ ПРОФЕСІЙНОЇ ЕТІОЛОГІЇ ТА ЕКОЛОГІЧНО ОБУМОВЛЕНИХ

DENSITOMETRY OF THE LUNGS IN THE ALGORITHM FOR THE DIAGNOSIS OF INTERSTITIAL LUNG DISEASES, INCLUDING OCCUPATIONAL AND ECOLOGICAL DISEASES A. V. Basanets, N. V. Kurdil Abstract Interstitial lung diseases are among the most common diseases of the respiratory system. A significant proportion of them are occupational diseases with pneumoconiosis as the most prevalent condition. Determination of lung density by computed densitometry (CD) allows to quantify the degree of density of lung tissue in a different lung diseases. This review focuses on world and domestic literature on the application of CD for the diagnosis and monitoring of management of interstitial lung diseases such as pulmonary sarcoidosis, pulmonary tuberculosis, idiopathic pulmonary fibrosis, pulmonary embolism, systemic sclerosis, pneumoconiosis, etc. The method of determining of lung density index, its effectiveness depending on the method of CT and the algorithm of examination of the patients are described. Peculiarities of changes in lung density index depending on the form and pathogenesis of the disease, its correlation with lung function and morphological changes have been analyzed. The most reproducible and perfect indicators of CD are those determined by inspiratory CT, which should be taken into account in the further improvement of research protocols. The standardization of the CT imaging protocol should be implemented taking into account the need for possible reduction of the radiation dose. Conclusions. The technique of CD is recognized as a revolutionary diagnostic tool for quantifying the density of the lung parenchyma, which can be effectively used to diagnose and verify the diagnosis of interstitial lung diseases, including occupational diseases. Improving methods of occupational and environmental interstitial lung diseases diagnosing, preventing their progression and development of complications will improve the quality of healthcare service for workers, decrease morbidity, reduce treatment and disability reimbursement costs. Key words: interstitial lung diseases, occupational diseases, computed lung densitometry, computed tomography

The therapeutic promises of Lianhuaqingke in the mice model of coronavirus pneumonia (HCoV-229E and SARS-CoV-2)

BackgroundLianhuaqingke (LHQK) has been approved for the treatment of acute tracheobronchitis and exerts a broad-spectrum antiviral effect in our previous study.MethodsAcute pneumonia caused by HCoV-229E was modeled in BALB/c mice. The anti-viral effect of LHQK was assessed by measuring the lung index and virus titer of lung tissues. The expression levels of pro-inflammatory cytokines in lung tissues and peripheral blood were measured by ELISA. The morphological changes of lung tissues were observed by H&E staining. The subsets of Th cells were assayed by the flow cytometry, including Th0, Th1, Th2, Treg, and Th17. The expression level of MUC5AC in 16HBE cells treated with TNFα was measured by ELISA. Immunofluorescence staining for β-IV tubulin was used to identify the airway epithelial ciliary in the condition-cultured RTE cells treated with TNFα. The direct antiviral effect of LHQK was assessed in vitro in Vero E6 infected by SARS-CoV-2, validated in vivo in the COVID-19 model of hACE2 transgenic mouse by detecting the lung index, the SARS-CoV-2 virus load, and the morphological changes of lung tissues.ResultsLHQK reduced the weight loss and the lung index by inhibiting the HCoV-229E replication and reducing the expression of pro-inflammatory cytokines in lung tissues. An assay for the Th cell subsets in peripheral blood revealed that LHQK could reduce the ratio of Th1/Th2 and increase the Treg/Th17 ratio in a dose-dependent way, which indicated that LHQK could coordinate the Th-mediated immune responses against the virus. In in vitro injury by TNFα, LHQK inhibited MUC5AC expression in 16HBE cells and increased the number of β-IV tubulin positive staining cells in the condition-cultured RTE cells. In the SARS-CoV-2-infected mice, LHQK could reduce weight loss, inhibit viral replication, and alleviate lung tissue damage.ConclusionsOur results demonstrate that LHQK exerts therapeutic effects on pneumonia caused by HCoVs (HCoV-229E and SARS-CoV-2) in mice, and that the anti-HCoV effects might depend on its immunomodulatory capacities. All these results suggest that LHQK serves as a potential adjuvant for anti-HCoV therapies.

Effect of electro-acupuncture at ST 36 on maternal food restriction-induced lung phenotype in rat offspring.

Maternal food restriction (MFR) during pregnancy leads to pulmonary dysplasia in the newborn period and increases susceptibility to diseases, such as asthma and chronic lung disease, later in life. Previous studies have shown that maternal electro-acupuncture (EA) applied to "Zusanli" (ST 36) could prevent the abnormal expression of key lung developmental signaling pathways and improve the lung morphology and function in perinatal nicotine exposed offspring. There is a significant overlap in lung developmental signaling pathways affected by perinatal nicotine exposure and MFR during pregnancy; however, whether maternal EA at ST 36 also blocks the MFR-induced lung phenotype is unknown. Here, we examined the effects of EA applied to maternal ST 36 on lung morphology and function and the expression of key lung developmental signaling pathways, and the hypercorticoid state associated with MFR during pregnancy. These effects were compared with those of metyrapone, an intervention known to block MFR-induced offspring hypercorticoid state and the resultant pulmonary pathology. Like metyrapone, maternal EA at ST 36 blocked the MFR-induced changes in key developmental signaling pathways and protected the MFR-induced changes in lung morphology and function. These results offer a novel and safe, nonpharmacologic approach to prevent MFR-induced pulmonary dysplasia in offspring.