Lung Histopathological Changes Research Articles

Exposure of calcium carbide induces apoptosis in mammalian fibroblast L929 cells

Inspite of various health warnings from Government and health organizations, Calcium carbide (CaC2) is still the most commonly and widely used artificial fruit ripener, probably due to its easy availability, low cost and convenience of usage. Assessment of the hazardous effects of the CaC2 applications for fruit ripening has been a matter of interest since long. Several in vivo studies have reported the toxicological outcomes such as histopathological changes in lungs and kidneys, haematological and immunological responses, upon exposure with CaC2. However, a well-controlled study investigating the effects of CaC2 under in-vitro setup was lacking. Hence, this study has been conducted to explore the toxicity associated cellular events in L929 cells exposed with varying concentrations of CaC2 (0.00312–0.2 μg/μl) for 24 h exposure time. A 23.14% reduction in cell viability was observed at the highest dose of CaC2. A similar trend in cellular stress levels at 0.2 μg/μl dose was observed in terms of rounded cellular morphology and decreased adherence as compared to the control. Furthermore, Annexin V FITC/PI staining and subsequent confocal imaging revealed a similar trend of CaC2 induced apoptosis in a dose dependent manner. A gradual elevation of intracellular ROS has also been observed up to 0.025 μg/μl dose. Thus, the study concludes that short term CaC2 exposure may increase the cellular oxidative stress and disturb the redox balance of the cell which then undergoes apoptosis. The study concludes that the exposure of CaC2 can be associated with severe diseases and suggests to stop the uses of CaC2 as fruit ripening agent.

Prenatal developmental toxicity studies on fumes from bitumen in the rat

The prenatal developmental toxicity of bitumen fume was tested by nose-only inhalation in the rat. The fumes for exposure were collected from the headspace of a storage tank filled with a bitumen corresponding in composition to an anticipated worst-case occupational exposure. The composition of these fumes was compared to actual paving site fumes to ensure its representativeness for workplace exposures. In a dose-range-finding study male and female rats were exposed to 0, 103, 480 or 1043 mg/m3 of fume (as total organic mass), for 6 h/day during 20 days post conception (p.c.). Dose-related effects on body weight and lungs were observed in the mid- and high-dose groups. In the main study, dams were exposed to 0, 52, 151 and 482 mg/m3 of fume, for 6 h/day during 19 days p.c. The maternal NOAEL was 52 mg/m³. In the high-dose group treatment-related effects on body weight (gain), food consumption, lung weights, and histopathological changes in lungs and larynx were observed. In the mid-dose group only histopathological changes in the larynx and lungs were found. The NOAEL for prenatal developmental toxicity was 151 mg/m³ based on reduced fetal weight in the high-dose group (482 mg/m³). However, these changes are most likely a consequence of the maternal toxicity, in particular the reduction of maternal body weight gain by 26 % as compared to control. Nose-only exposure to bitumen fumes in concentrations up to 482 mg/m³ from days 1–19 p.c. did not induce any significant fetal anomalies.

Ferulic acid alleviates lipopolysaccharide-induced acute lung injury through inhibiting TLR4/NF-κB signaling pathway.

Ferulic acid (FA) exhibits anti-inflammatory, antidiabetic, antihyperlipidemic, antioxidant, neuroprotective, and antihypertensive effects. This study aimed to determine whether FA could ameliorate lipopolysaccharide (LPS)-induced inflammatory responses and acute lung injury (ALI) in mice. Mice were challenged with LPS intratracheally to induce ALI 1 h after 3 days of FA (25, 50, and 100 mg/kg) or dexamethasone (DEX; 5 mg/kg) administration. The lung tissues and bronchoalveolar lavage fluid (BALF) were collected 12 h after the LPS challenge. Pretreatment with FA or DEX could attenuate lung histopathological change, complement deposition, and lung wet-to-dry weight ratio of mice injured by LPS. Meanwhile, the influx of neutrophils and macrophages, as well as the production of proinflammatory cytokine (tumor necrosis factor-alpha, interleukin 1 beta [IL-1β], and IL-6), in BALF of ALI mice was significantly decreased. Moreover, FA or DEX markedly reversedthe LPS-induced elevation of myeloperoxidase activity and monocyte chemoattractant protein-1 level in lung tissues of ALI mice. In addition, the Western blot analysis demonstrated that FA or DEX effectively inhibited the LPS-induced activation of the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway in lung tissues. The current study suggested that the alleviating effect of FA against LPS-induced ALI might be partially due to the inhibition of the inflammatory response via inactivation of the TLR4/NF-κB signaling pathway.

AITC induces MRP1 expression by protecting against CS/CSE-mediated DJ-1 protein degradation via activation of the DJ-1/Nrf2 axis.

The present study aimed to examine the effect of allyl isothiocyanate (AITC) on chronic obstructive pulmonary disease and to investigate whether upregulation of multidrug resistance-associated protein 1 (MRP1) associated with the activation of the PARK7 (DJ-1)/nuclear factor erythroid 2-related factor 2 (Nrf2) axis. Lung function indexes and histopathological changes in mice were assessed by lung function detection and H&E staining. The expression levels of Nrf2, MRP1, heme oxygenase-1 (HO-1), and DJ-1 were determined by immunohistochemistry, Western blotting and reverse transcription-quantitative polymerase chain reaction. Next, the expression of DJ-1 in human bronchial epithelial (16HBE) cells was silenced by siRNA, and the effect of DJ-1 expression level on cigarette smoke extract (CSE)-stimulated protein degradation and AITC-induced protein expression was examined. The expression of DJ-1, Nrf2, HO-1, and MRP1 was significantly decreased in the wild type model group, while the expression of each protein was significantly increased after administration of AITC. Silencing the expression of DJ-1 in 16HBE cells accelerated CSE-induced protein degradation, and significantly attenuated the AITC-induced mRNA and protein expression of Nrf2 and MRP1. The present study describes a novel mechanism by which AITC induces MRP1 expression by protecting against CS/CSE-mediated DJ-1 protein degradation via activation of the DJ-1/Nrf2 axis.

Sequential Co-infection of Heligmosomoides polygyrus and Mycobacterium tuberculosis Determine Lung Macrophage Polarization and Histopathological Changes

BackgroundTuberculosis is a chronic infection caused by Mycobacterium tuberculosis (M.tb), which needs proper macrophage activation for control. It has been debated whether the co-infection with helminth will affect the immune response to mycobacterial infection. ObjectiveTo determine the effect of sequential co-infection of Heligmosomoides polygyrus (H.pg) nematodes and M.tb on T cell responses, macrophages polarization and lung histopathological changes. MethodThis study used 49 mice divided into 7 treatment groups, with different sequence of infection of M.tb via inhalation and H.pg via oral ingestion for 8 and 16 weeks. T cells response in the lung, intestine, and peripheral blood were determined by flow cytometry. Cytokines (IL-4, IFN-γ, TGB-β1, and IL-10) were measured in peripheral blood using ELISA. Lung macrophage polarization were determined by the expression of iNOS (M1) or Arginase 1 (M2). Mycobacterial count were done in lung tissue. Lung histopathology were measured using Dorman’s semiquantitative score assessing peribronchiolitis, perivasculitis, alveolitis, and granuloma formation. ResultM.tb infection induced Th1 response and M1 macrophage polarization, while H.pg infection induced Th2 and M2 polarization. In sequential co-infection, the final polarization of macrophage was dictated by the sequence of co-infection. However, all groups with M.tb infection showed the same degree of mycobacterial count in lung tissues and lung tissue histopathological changes. ConclusionSequential co-infection of H.pg and M.tb induces different T cell response which leads to different macrophage polarization in lung tissue. Helminth infection induced M2 lung macrophage polarization, but did not cause different mycobacterial count nor lung histopathological changes.

Ganoderic acid B attenuates LPS-induced lung injury

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a serious respiratory disease, the mechanism is unclear. This paper revealed the mechanism of ganoderic acid B (BB) on lipopolysaccharide-induced pneumonia in mice. Pneumonia model was induced by LPS in mice and A549 cells. Lung dry/wet weight (W/D) and myeloperoxidase (MPO) activity in lung were examined. Lung histopathological changes was observed by HE staining. Superoxide dismutase (SOD), malondialdehyde (MDA) and proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in mice and A549 cells were detected. Rho/NF-κB pathway in mice and A549 cells were examined by Western Blot. BB significantly reduced W/D and MPO activity, restored lung histopathological changes. BB also increased SOD, decreased MDA, TNF-α, IL-1β and IL-6 in mice and A549 cells. In addition, BB inhibited Rho/NF-κB pathway in mice and A549 cells. BB has protective effect on LPS-induced pneumonia in mice, and its mechanism is related to the regulation of Rho/NF-κB signaling pathway.

Modulation of bleomycin-induced oxidative stress and pulmonary fibrosis by N-acetylcysteine in rats via AMPK/SIRT1/NF-κβ.

The efficacy of bleomycin (BLM) as an antineoplastic drug is limited to the development of dose and time-dependent pulmonary fibrosis. This study was intended to investigate the effect of N-acetylcysteine (NAC) on BLM-induced pulmonary fibrosis in rats. Twenty rats were randomly divided to the following four groups: Group one served as control; group two received BLM (15mg/kg, intraperitoneal (ip)) for five consecutive days; group three received NAC (200mg/kg, ip) for five consecutive days; and group four received NAC 1hour before BLM for 5days. The expression of connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF), silent information regulator l (SIRT1), AMP-activated protein kinase (AMPK) were determined by qRT-PCR in lung tissues. The changes in transforming growth factor-beta1 (TGF-β1), tumour necrosis factor-α (TNF-α), interleukin-β1 (IL-β1) and nuclear factor kappa-β (NF-κβ) in serum were measured by ELISA. The tissue antioxidant status was determined biochemically. BLM administration caused pulmonary fibrosis as evidenced by increased levels of inflammatory mediators (TGF-β1, TNF-α, IL-β1 and NF-κβ) in serum (P<.05), elevated lipid peroxidation and nitric oxide and depleted endogenous antioxidants in lung tissue (P<.05). The expression levels of SIRT1 and AMPK were significantly decreased (P<.05), while the expression levels of CTGF and PDGF were increased significantly in the BLM group as compared to the control group (P<.05). These alterations were normalized by NAC intervention. NAC markedly attenuated the lung histopathological changes and reduced collagen deposition. These results suggest that NAC exerted an ameliorative effect against BLM-induced oxidative damage and pulmonary fibrosis via SIRT1/ AMPK/ NF-κβ pathways.

A Demographic Study on Cases of Drowning with Special Reference to Histopathological Changes of Lung and Other Tissues in a Tertiary Centre

Introduction:Drowning is the 3rd leading cause of unintentional injury deaths.As drowning is a preventable cause of mortality, our aims for the benefit of society at large is to minimize the events as far as possible. Objective:A clear knowledge about factors which play a major role behind such incidences is important.It has equal forensic importance as determination of cause and manner of death require thorough investigation. Methodology: We conducted one-year study of demographic variables and the histopathological changes in relation to lung and splenic tissues in cases of drowning deaths, in the hot and humid climatic region of Eastern India.Results: The demographic findings were presented in graphs and charts. However, none of the commonly known autopsy findings (histopathological) are found to be individually confirmatory of drowning. Conclusion:Several factors inclusive of autopsy findings, biochemical examination, radiological and molecular technique,are needed to be taken together as complementary methods to conclude drowning as the cause of death when bodies are recovered from water.

S-allylmercaptocysteine inhibits mucin overexpression and inflammation via MAPKs and PI3K-Akt signaling pathways in acute respiratory distress syndrome

Cytokine storm is an important cause of acute respiratory distress syndrome and multiple organ failure. Excessive secretion and accumulation of mucins on the surface of airway cause airway obstruction and exacerbate lung infections. MUC5AC and MUC5B are the main secreted mucins and overexpressed in various inflammatory responses. S-allylmercaptocysteine, a water-soluble organic sulfur compound extracted from garlic, has anti-inflammatory and anti-oxidative effects for various pulmonary diseases. The aim of this work was to investigate the therapeutic effects of SAMC on mucin overproduction and inflammation in 16HBE cells and LPS-induced ARDS mice. Results show that SAMC treatment ameliorated inflammatory cell infiltration and lung histopathological changes in the LPS-induced ARDS mice. SAMC also inhibited the expressions of MUC5AC and MUC5B, decreased the production of pro-inflammatory markers (IL-6, TNF-α, CD86 and IL-12) and increased the production of anti-inflammatory markers (IL-10, CD206 and TGF-β). These results confirm that SAMC had potential beneficial effects on suppressed hyperinflammation and mucin overexpression. Furthermore, SAMC exerted the therapeutic effects through the inhibition of phosphorylation of MAPKs and PI3K-Akt signaling pathways in the 16HBE cells and mice. Overall, our results demonstrate the effects of SAMC on the LPS-induced mucin overproduction and inflammation both in the 16HBE cells and mice.

Antibacterial efficacy of R-type pyocins against Pseudomonas aeruginosa on biofilms and in a murine model of acute lung infection.

The appearance of MDR strains and the development of biofilms make Pseudomonas aeruginosa infections a therapeutic challenge. To overcome this scenario, bacteriocins have been proposed as a potential adjuvant or alternative to antibiotic treatment. To study the activity of R-pyocins on biofilms and in a murine model of pneumonia using a high-risk clone of P. aeruginosa. The activity of R-pyocins on P. aeruginosa biofilms was tested on bacteria attached to a silicone surface, before and after biofilm formation. The effectiveness of R1-pyocin was studied in a murine model of pneumonia using ST175, a high-risk clone of P. aeruginosa. R-pyocins attacked adherent bacteria, preventing biofilm formation, and penetrated into the biofilm, killing P. aeruginosa within it, resulting in a dramatic reduction in bacterial load. R1-pyocin was active in a murine model of P. aeruginosa lung infection, administered before infection as a preventive treatment, and in acute pneumonia, with efficiency higher than standard colistin treatment. In addition, this work is the first to describe histopathological lung changes after administration of R-pyocins, contributing to the resolution of P. aeruginosa pneumonia in a murine model. This work highlights the potential use of the R-pyocins as therapeutic agents, alone or as adjuvants, due to its effectiveness on biofilms and in a murine model of pneumonia using ST175, a high-risk clone of P. aeruginosa. It may thus be feasible to consider R-pyocins as a possible therapeutic alternative in XDR infections, where treatment alternatives are limited.

Aloin suppresses lipopolysaccharide-induced acute lung injury by inhibiting NLRP3/NF-κB via activation of SIRT1 in mice

Objective The purpose of this study was to explore the protective effects and potential mechanisms of aloin on lipopolysaccharide (LPS)-induced acute lung injury (ALI). Methods Mice were pretreatment with aloin 1 h before LPS administration. The number of inflammatory cells and the levels of TNF-α and IL-1β was detected. The lung histopathological changes, wet/dry ratio, MPO activity, GSH, MDA, SOD, and the expression of NF-κB and NLRP3 inflammasome were measured. Results The results showed that aloin significantly inhibited the number of total cells, neutrophils, and macrophages, as well as the levels of TNF-α and IL-1β in BALF induced by LPS. In addition, pretreatment with aloin also inhibited LPS-induced lung histopathological injuries, lung wet/dry ratio, MPO activity, and MDA content. The levels of GSH and SOD were decreased by LPS and treatment of aloin could increase the levels of GSH and SOD. To study the protective mechanisms of alion on LPS-induced ALI, the expression of SIRT1, NF-κB and NLRP3 inflammasome were tested. We found that aloin significantly inhibited the activation of NF-κB and NLRP3 inflammasome in ALI induced by LPS. Meanwhile, aloin was found to increase the expression of SIRT1 and inhibition of SIRT1 by EX-527 reversed the protective effects of aloin. Conclusions These results suggest that aloin exerts its protective effects on LPS-induced ALI by activation SIRT1, which subsequently results in the suppression of NF-κB and NLRP3 inflammasome.

Oral administration of polyphenol-rich Sargassum horneri suppresses particulate matter exacerbated airway inflammation in murine allergic asthma: Relevance to the TLR mediated NF-κB pathway inhibition

• Polyphenol rich Sargassum horneri extract (SHE) attenuates inflammatory responses in asthmatic mice. • SHE attenuates particulate matter (PM)-induced histopathological changes in lung. • SHE suppresses PM-induced TLR2/4/7 activation and downstream signaling cascade along the NF-κB pathway in lung. Particulate matter (PM) is known to exacerbate airway inflammatory responses in asthma patients and to worsen asthma symptoms. Hypothesizing that attenuating airway inflammation might delay the exacerbation of PM-induced asthma symptoms, we investigated polyphenol-containing Sargassum horneri extract’s (SHE’s) anti-inflammatory efficacy and its underlying mechanism against PM–exacerbated inflammatory response using an asthma mouse model. SHE attenuated the PM–aggravated granulocytes infiltration into the airway and suppressed the PM-exacerbated mRNA expression of TLRs (TLR2/4/7), leading to the reduction of MyD88 dependent NF-κB activation in lungs of asthmatic mice. This resulted in attenuated PM-exacerbated mRNA expression of pro-inflammatory cytokines (IL-1β, TNF-α, TGF-β, IL-6), pro-allergic cytokines (TSLP, IL-25, IL-33), and a chemokine (IL-8) in lungs of asthmatic mice. Taken together, we conclude that SHE mitigates the PM-exacerbated airway inflammatory response of asthmatic mice via modulating TLR2/4/7 mediated MyD88 dependent NF-κB pathway and might make a natural candidate against the PM exacerbated severe asthma.

Exposure to Air Pollution Exacerbates Inflammation in Rats with Preexisting COPD.

Particulate matter with an aerodynamic diameter equal or less than 2.5 micrometers (PM2.5) is associated with the development of chronic obstructive pulmonary disease (COPD). The mechanisms by which PM2.5 accelerates disease progression in COPD are poorly understood. In this study, we aimed to investigate the effect of PM2.5 on lung injury in rats with hallmark features of COPD. Cardinal features of human COPD were induced in a rat model by repeated cigarette smoke inhalation and bacterial infection for 8 weeks. Then, from week 9 to week 16, some of these rats with COPD were subjected to real-time concentrated atmospheric PM2.5. Lung function, pathology, inflammatory cytokines, oxidative stress, and mucus and collagen production were measured. As expected, the COPD rats had developed emphysema, inflammation, and deterioration in lung function. PM2.5 exposure resulted in greater lung function decline and histopathological changes, as reflected by increased Mucin (MUC) 5ac, MUC5b, Collagen I, Collagen III, and the profibrotic cytokine α-smooth muscle-actin (SMA), transforming growth factor- (TGF-) β1 in lung tissues. PM2.5 also aggravated inflammation, increasing neutrophils and eosinophils in bronchoalveolar lavage fluid (BALF) and cytokines including Interleukin- (IL-) 1β, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-4. The likely mechanism is through oxidative stress as antioxidants levels were decreased, whereas oxidants were increased, indicating a detrimental shift in the oxidant-antioxidant balance. Altogether, these results suggest that PM2.5 exposure could promote the development of COPD by impairing lung function and exacerbating pulmonary injury, and the potential mechanisms are related to inflammatory response and oxidative stress.

Establishment of a novel mouse mode of elastase-induced chronic obstructive pulmonary disease related osteoporosis

To establish and evaluate the model of chronic obstructive pulmonary disease (COPD) with osteoporosis induced by elastase in mice. Twenty four healthy female 8-week-old C57BL / 6 mice (weighing about 18 g) were randomly divided into three groups. The control group was given intratracheal drip of normal saline, the experimental group 1 and the experimental group 2 were given intratracheal drip of elastase, the control group and the experimental group 1 were kept for 8 weeks and then killed, the experimental group 2 was kept for 12 weeks and then killed. HE staining was used to evaluate the histopathological changes of lung and tibia in the control and experimental groups. The levels of serum inflammatory factors and broncho alveolar lavage factors (BALF) were detected by ELISA. Micro CT was used to detect the bone mass related parameters of mouse femur. The expression of osteoclastic and osteogenic genes was detected by real-time fluorescence quantitative PCR. Lung histopathology showed that the structure of alveoli in the experimental group was disordered, the walls of alveoli became thin or broken, and the alveoli cavity expanded. IL-6 and TNF-α in BALF were significantly higher than those in control group (P<0.001), while IL-1β and TNF-α in serum inflammatory factors were significantly higher than those in control group (P<0.001). BV / TV(bone volume fraction), TB.Th(average bone trabecular thickness) and TB.N(average bone trabecular number) in the experimental group were significantly lower than those in the control group (P<0.05), TB.Sp (average bone trabecular separation) and BS / BV (bone surface area fraction) in the experimental group were significantly higher than those in the control group (P<0.01). Compared with the control group, the expression of osteoclast related marker genes increased in the experimental group (P<0.05), but decreased in the experimental group(P<0.05). The results of experiment 1 and experiment 2 were time-dependent. In this study, elastase was used to construct a COPD model with osteoporosis successfully, which provides a suitable animal model for the future study of the pathogenesis of COPD with osteoporosis.

Inhibition of Rb phosphorylation leads to H2S-mediated inhibition of NF-kB in acute pancreatitis and associated lung injury in mice

BackgroundAcute pancreatitis (AP), an inflammatory condition of pancreas, destructs the exocrine cells by releasing various pro-inflammatory cytokines that activates the stellate cells. However, the underlying molecular mechanism remains unclear. The present study investigated the role of retinoblastoma (Rb), hydrogen sulphide and nuclear factor-κB (NF-κB) in the regulation of exocrine cell proliferation under inflammatory condition. MethodsThe randomly grouped male swiss mice were administered with 6 consecutive hourly i.p injections of caerulein to induce AP. Palbociclib (PD) (25 mg/kg body weight), a CDK4/6 inhibitor, was administered 1 h after the first cerulein injection intraperitoneally to block the RB pathway by inhibiting the activity of the CDK4/6 complexes and DL propargylglycine (PAG) which blocks the endogenous H2S production. ResultsPharmacological inhibition of CDK4/6 and H2S significantly improved pancreas and lung histopathological changes, decreased serum amylase level, both lung and pancreas myeloperoxidase (MPO) activity, TNFα expression and elevated IL10 expression. Furthermore, inhibition of RB pathway reduced cerulein-induced H2S level by reducing the expression of cystathionine gamma lyase (CSE) and NF-κB activation in pancreas and lungs. Also, blocking the RB signalling reduced the α-SMA expression in pancreas preventing the risk for pancreatic fibrosis. Whereas administration of H2S inhibitor PAG resulted in a decrease in CDK4/6-Rb expression in cerulein-induced AP. ConclusionThese results reveal a novel link between H2S/RB/NF-κB pathways, in AP and provide insight into possible mechanism that can be targeted in prevention of inflammation to cancer development.

Differential expression of caveolin-1 during pathogenesis of combined pulmonary fibrosis and emphysema: Effect of phosphodiesterase-5 inhibitor

IntroductionCombined pulmonary fibrosis and emphysema (CPFE) is a relatively new entity within the spectrum of cigarette smoke induced lung disorders. Currently there is no consensus about its treatment. We hypothesized that caveolin-1 critically determines the parenchymal and vascular remodeling leading to the development of CPFE. We assessed the effect of therapeutic targeting of caveolin-1 in mesenchymal and endothelial cells by the phosphodiesterase-5 inhibitor, sildenafil. MethodsMale Wistar rats (n = 168) were exposed to; room air (control); bleomycin (7 U/kg), bleomycin+sildenafil (50 mg/kg/day P.O.), cigarette smoke (CS) (4 Gold Flake 69 mm/day), CS + sildenafil, CS + bleomycin, CS + bleomycin+sildenafil. Animals were euthanized at 8, 9, 11, 12 weeks and lung histopathological changes, collagen deposition, ROS, Xanthine oxidase, caveolin-1 determined. ResultsCigarette smoke causes progressive ROS accumulation, caveolin-1 up-regulation in alveolar epithelial cells, alveolar macrophages, peribronchiolar fibroblasts, endothelial and vascular smooth muscle cells, interstitial inflammation and emphysema. Sildenafil reduces oxidative stress, parenchymal caveolin-1 and attenuates emphysema caused by CS. Bleomycin increases lung ROS and downregulates caveolin-1 leading to fibroblast proliferation and fibrosis. Combined cigarette smoke and bleomycin exposure, results in differential caveolin-1 expression and heterogeneous parenchymal remodeling with alternating areas of emphysema and fibrosis. Increased caveolin-1 induces premature senescence of lung fibroblasts and emphysema. Decreased caveolin-1 is associated with propagation of EMT and fibrosis. Sildenafil attenuates the parenchymal remodeling however it is not effective in reducing VSMC hypertrophy in combined group. ConclusionCPFE is characterized by heterogenous parenchymal remodeling and differential caveolin-1 expression. Sildenafil therapy attenuates parenchymal pathologies in CPFE. Additional therapy is however needed for attenuating VSMC remodeling.

STAT3 decoy oligodeoxynucleotides improve end‐organ tissue injury and survival in septic mice

STAT3 serves as a key transcription factor in both immunity and inflammatory pathways. We examined whether in vivo introduction of STAT3 decoy oligodeoxynucleotides (ODNs) is beneficial in reducing septic end‐organ injury. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in mice. STAT3 was rapidly activated in major end‐organ tissues following CLP, which was accompanied by activation of the upstream kinase JAK2. Transfection of STAT3 decoy ODNs significantly improved histopathological changes in lung, liver, kidney, and heart tissues. STAT3 decoy ODN transfection downregulated pro‐inflammatory cytokine/chemokine overproduction and reduced the increases in tissue and serum levels of HMGB1 in CLP mice. These beneficial effects of STAT3 decoy ODNs led to s significant survival advantage in mice after CLP. Our results indicate a detrimental role of STAT3 in the sepsis pathophysiology and the potential usefulness of STAT3 decoy ODNs for sepsis therapy.Support or Funding InformationGrants‐in‐Aid for Scientific Research from Japan Society for Promotion of Science (17K08586, 19H03757)

Naringin Attenuated Acute Lung Injury in Rat Model with Acute Pancreatitis in Pregnancy through Inactivation of p38 MAPK Pathway

Acute pancreatitis in pregnancy can cause fetal lung injury. Naringin exhibits ant-inflammation effect against pulmonary injuries. However, whether naringin can alleviate lung injury associated with acute pancreatitis in pregnancy has not been elucidated. Establishment of acute pancreatitis in pregnancy model by sodium taurocholate showed that sodium taurocholate induced obvious pathological changes in pancreas. Histopathological changes in lungs were also aggravated post sodium taurocholate treatment with enhanced inflammation of neutrophils, thickened alveolar walls and alveolus collapse. Diagnostic blood tests for acute pancreatitis in pregnancy indicated that serum amylase and lipase were increased post sodium taurocholate treatment. Sodium taurocholate-induced rats were intragastrically administered with naringin to investigate the protective effect of naringin on acute lung injury induced by acute pancreatitis in pregnancy. Results revealed that administration of naringin could attenuate pathological changes in pancreas and lungs and decrease amylase and lipase. Moreover, naringin treatment attenuated sodium taurocholate-induced increase in inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6/1β in lungs. Sodium taurocholate-induced increase in phosphorylation of p38 was also reduced post naringin treatment. In conclusion, naringin could ameliorate acute lung injury and inflammation induced by acute pancreatitis in pregnancy by inhibiting the p38 pathway.

Histopathological basis of COVID-19: A short review

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the global pandemic in 2020 resulting a massive morbidity &amp; mortality. The lung is the predominant organ involved in symptomatic patients with Coronavirus disease-2019 (COVID-19) along with involvement of other organs. Understanding the histopathological changes of lung and other organs in COVID-19 become essential for not only formulating future management protocols but also for determing prognosis. The collection of potentially contaminated tissues during the autopsy and further processing of them in histopathology laboratory with proper maintenance of safety protocol is of immense importance. A review of the available scientific articles shows the diffuse alveolar damage and microvascular thrombi are common observation found in lung tissue in patients who died due to COVID-19.

The Mechanisms Involved in Mesenchymal Stem Cell Alleviation of Sepsis-Induced Acute Lung Injury in Mice: A Pilot Study

BackgroundAcute lung injury is a common complication of sepsis in intensive care unit patients. Inflammation is among the main mechanisms of sepsis. Therefore, suppression of inflammation is an important mechanism for sepsis treatment. Mesenchymal stem cells (MSCs) have been reported to exhibit antimicrobial properties.ObjectiveThe present study investigated the effects of MSCs on sepsis-induced acute lung injury.MethodsMale C57BL/6 mice underwent a cecal ligation and puncture (CLP) operation to induce sepsis and then received either normal saline or MSCs (1 × 106 cells intravenously) at 3 hours after surgery. Survival after surgery was assessed. Lung injury was assessed by histology score, the presence of lung edema, vascular permeability, inflammatory cell infiltration, and cytokine levels in bronchoalveolar lavage fluid. Finally, we tested nuclear factor kappa-light-chain-enhancer of activated B cells activation in lung tissue.ResultsAs expected, CLP caused lung injury as indicated by significant increases in the histopathology score, lung wet to dry weight ratio, and total protein concentration. However, mice treated with MSCs had amelioration of the lung histopathologic changes, lung wet to dry weight ratio, and total protein concentration. The levels of cytokines tumor necrosis factor alpha, interleukin 6, interleukin 1β, and interleukin 17 in bronchoalveolar lavage fluid were dramatically decreased after MSCs treatment. In contrast, expression of interleukin 10 was increased after MSCs treatment. Moreover, mice treated with MSCs had a higher survival rate than the CLP group. Neutrophil infiltration into bronchoalveolar lavage fluid was attenuated after MSCs injection, but the amounts of macrophages observed in the MSC group showed no significant differences compared with the CLP group. In addition, MSCs treatment significantly reduced nuclear factor kappa-light-chain-enhancer of activated B cells activation in lung tissue.ConclusionsBased on the above findings, treatment with MSCs dampened the inflammatory response and inhibited nuclear factor kappa-light-chain-enhancer of activated B cells activation in the mouse CLP model. Thus, MSCs may be a potential new agent for the treatment of sepsis-induced acute lung injury. (Curr Ther Res Clin Exp. 2020; 81:XXX–XXX)