Lung Histopathological Changes Research Articles

Hyperbaric oxygen-induced acute lung injury: A mouse model study on pathogenic characteristics and recovery dynamics.

Oxygen is an essential substance for the maintenance of human life. It is also widely used in clinical and diving medicine. Although oxygen is crucial for survival, too much oxygen can be harmful. Excessive oxygen inhalation in a short period of time can lead to injury, and the lung is one of the main target organs. Acute lung injury (ALI) induced by hyperbaric oxygen (HBO) is notably more severe than that caused by normobaric oxygen, yet systematic research on such injury and its regression is scarce. In this study, two independent experiments were designed. In the first experiment, mice were exposed to 2 atmospheres absolute (ATA), ≥95% oxygen for 2, 4, 6, and 8 h. Changes in lung histopathology, inflammation and expression of chemokines, alveolar-capillary barrier, and 8-OHdG were detected before and after the exposure. In the second experiment, these parameters were measured at 0 h, 12 h, and 24 h following 6 h of exposure to 2 ATA of ≥95% oxygen. Research indicates that ALI induced by HBO is characterized histologically by alveolar expansion, atelectasis, inflammatory cell infiltration, and hemorrhage. At 2 ATA, significant changes in the alveolar-capillary barrier were observed after more than 95% oxygen exposure for 4 h, as evidenced by increased Evans blue (EB) extravasation (p = 0.0200). After 6 h of HBO exposure, lung tissue pathology scores, 8-OHdG levels, and inflammatory and chemotactic factors (such as Il6, CCL2, CCL3, CXCL5, and CXCL10), intercellular adhesion molecule 1 (ICAM1), and vascular cell adhesion molecule 1 (VCAM1) were significantly elevated. Compared to lung injury caused by normobaric oxygen, the onset time of injury was significantly shortened. Additionally, it was observed that these markers continued to increase after leaving the HBO environment, peaking at 12 h and starting to recover at 24 h, indicating that the peak of inflammatory lung injury occurs within 12 h post-exposure, with recovery beginning at 24 h. This contradicts the common belief that lung injury is alleviated upon removal from a high-oxygen environment. However, EB levels, which reflect damage to the alveolar-capillary barrier, and VE-Cadherin (VE-Cad), tight junction protein 1 (ZO-1), ICAM1, and VCAM1 remained significantly altered 24 h after leaving the HBO environment. This suggests that the alveolar-capillary barrier is the most sensitive and slowest recovering part of the lung injury induced by HBO. These findings can provide insights into the pathogenesis and progression of lung injury caused by HBO and offer references for identifying corresponding intervention targets.

A Prospective Study Of Histo-Pathological Changes In Lungs, Liver And Kidneys In Burns Cases Autopsied At A Tertiary Care Hospital

Introduction: Medico legal deaths including burns claim a substantial number of lives in central Karnataka.‘A Prospective Study of Histo-Pathological changes in Lungs, Liver and Kidneys in Burns Cases’ was carried out at the Department of Forensic Medicine & Toxicology, SS hospital, SSIMS & RC, Davangere. Material & methods: The present study was carried out for the period of 3 years from January 2021 to December2023. Totally 100 cases with burns and scalds injuries brought to the mortuary for autopsy was the material for study and collection of tissues for histopathological examination. Observations & Results: In the present study, histopathological changes in lungs showed congestion, pulmonary edema, Diffuse alveolar damage or ARDS changes, bronchopneumonia, interstitial pneumonitis, anthracotic pigment, carbon laden macrophages, intravascular thrombi, septic emboli, interstitial & intra alveolar hemorrhage. Histopathological changes in liver showed congestion, fatty change, centrilobular necrosis, cloudy swelling, focal hemorrhage, necrosis, portal inflammation. Histopathological changes in kidneys showed ATN in majority of cases, cloudy degeneration, congestion, tubular casts and acute pyelonephritis in rest of the cases. Conclusion: The effect of burns on vital organs can be assessed through histopathological examination, which helps in determining the post burn complications and which aid in better treatment outcome of the burn’s patients.

Hepatoprotective effects of vildagliptin mitigates lung biochemical and histopathological changes in experimental hepatopulmonary syndrome model in rat

Hepatopulmonary syndrome (HPS) is a liver disease-induced pulmonary complication manifested with arterial hypoxemia. Hepatic cholestasis, encountered in several clinical situations, leads to biliary cirrhosis and HPS, both of which are best reproduced by rat common bile duct ligation (CBDL). Experience from liver transplantation suggests hepatoprotective-based therapy would be most effective in HPS treatment Dipeptidyl peptidase-4 (DPP-4) enzyme is involved in different pathogenic mechanisms of liver diseases. Vildagliptin (Vild) is a DPP-4 inhibitor which possesses favorable anti-inflammatory, anti-oxidant and anti-fibrotic effects. The present work explored hepatoprotective mechanisms of Vild and their participation in its prophylactic effectiveness in HPS induced by CBDL in rats. Male Wistar rats weighing 220–280 g were allocated into 4 groups: normal control, sham, CBDL and CBDL + Vild groups. i.p. saline was administered to the first 3 groups and i.p. Vild (10 mg/kg/day) was given to the fourth group for 6 weeks starting 2 week before CBDL. CBDL produced liver fibrosis, arterial hypoxemia and decreased survivability of rats. It altered liver functions and induced oxidative stress, pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)], vasodilatory molecules [endothelin-1 (ET-1), and inducible and endothelial nitric oxide synthases] and angiogenesis-associated protein [vascular endothelial growth factor-A (VEGF-A)] in liver and lung. Vild ameliorated liver fibrosis, and improved hypoxemia and survivability of CBDL rats and reversed these biochemical alterations. Prophylactic Vild administration attenuated CBDL-induced HPS in rats via direct hepatoprotective effects in the form of anti-oxidant, anti-inflammatory, anti-angiogenic and anti-fibrotic effects beside inhibition of pathological intrahepatic vasodilatation.

Virulence and tissue tropism of different epidemiologically significant SARS-CoV-2 variants for golden Syrian hamsters

Introduction. Animal models for SARS-CoV-2 infection, reproducing the clinical features of COVID-19 in humans, are important tools for studying the pathogenesis of the disease, transmission of the pathogen and are indispensable for testing antiviral drugs and vaccines. The aim of the study was to assess the virulence and tissue tropism for golden Syrian hamsters of SARS-CoV-2 strains belonging to different epidemiologically significant variants: Wuhan-like, Delta, Omicron BA.1.1 and Omicron BA.5.2. Materials and methods. Hamsters were intranasally infected with different SARS-CoV-2 strains. Virulence and tissue tropism of SARS-CoV-2 strains were assessed by comparing the dynamics of weight, viral load in organs and histopathological changes in lungs in infected and uninfected animals. Results. The Wuhan-like Dubrovka strain had the greatest virulence for hamsters, which was manifested by the development of severe pneumonia and a delay in weight gain by 14.6%, high virus content in the lungs, nasal passages and brain — 6.2, 5,9 and 3.7 lg TCID50/ml of homogenate, respectively. Presumably, it was the infection of the Wuhan-like virus of the central nervous system that negatively affected the weight and general condition of the animals. When hamsters were infected with viruses belonging to the Delta and Omicron variants, the observed minor weight loss in animals was uninformative, so indicators such as lung histopathology, viral load in the lungs, nasal passages, heart and other organs played a decisive role in assessing the virus pathogenicity. A score assessment of lung histopathology was of particular value in assessing the severity of pneumonia, since it reduced subjectivity in evaluating the results of histological examination and provided a semi-quantitative assessment of the pathological process. Conclusion. Despite the revealed lower virulence for hamsters of viruses belonging to the Delta and Omicron variants compared to the ancestral Wuhan virus, this animal model for COVID-19 retains its value for conducting preclinical trials of antiviral drugs.

The effects of iron deficient and high iron diets on SARS-CoV-2 lung infection and disease.

The severity of Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often dictated by a range of comorbidities. A considerable literature suggests iron deficiency and iron overload may contribute to increased infection, inflammation and disease severity, although direct causal relationships have been difficult to establish. Here we generate iron deficient and iron loaded C57BL/6 J mice by feeding standard low and high iron diets, with mice on a normal iron diet representing controls. All mice were infected with a primary SARS-CoV-2 omicron XBB isolate and lung inflammatory responses were analyzed by histology, immunohistochemistry and RNA-Seq. Compared with controls, iron deficient mice showed no significant changes in lung viral loads or histopathology, whereas, iron loaded mice showed slightly, but significantly, reduced lung viral loads and histopathology. Transcriptional changes were modest, but illustrated widespread dysregulation of inflammation signatures for both iron deficient vs. controls, and iron loaded vs. controls. Some of these changes could be associated with detrimental outcomes, whereas others would be viewed as beneficial. Diet-associated iron deficiency or overload thus induced modest modulations of inflammatory signatures, but no significant histopathologically detectable disease exacerbations.

Perilla frutescens leaf extracts alleviate acute lung injury in mice by inhibiting KAT2A

Ethnopharmacological relevanceAcute lung injury (ALI) can lead to respiratory failure and even death. KAT2A is a key target to suppress the development of inflammation. A herb, perilla frutescens, is an effective treatment for pulmonary inflammatory diseases with anti-inflammatory effects; however, its mechanism of action remains unclear.Aim of the study: The purpose of this study was to investigate the therapeutic effect and underlying mechanism of perilla frutescens leaf extracts (PLE), in the treatment of ALI by focusing on its ability to treat inflammation. Materials and methodsIn vivo and in vitro models of ALI induced by LPS. Respiratory function, histopathological changes of lung, and BEAS-2B cells damage were assessed upon PLE. This effect is also tested under conditions of KAT2A over expression and KAT2A silencing. ResultsPLE significantly attenuated LPS-induced histopathological changes in the lungs, improved respiratory function, and increased survival rate from LPS stimuation background in mice. PLE remarkably suppressed the phosphorylation of STAT3, AKT, ERK (1/2) and the release of cytokines (IL-6, TNF-α, and IL-1β) induced by LPS via inhibiting the expression of KAT2A. ConclusionsPLE has a dose-dependent anti-inflammatory effect by inhibiting KAT2A expression to suppress LPS-induced ALI n mice. Our study expands the clinical indications of the traditional medicine PLE and provide a theoretical basis for clinical use of acute lung injury.

Changes of lung function and inflammatory factors in rat models of coal workers' pneumoconiosis

Objective: To observe the changes of lung function and inflammatory factors in rat models of coal workers' pneumoconiosis at different time points. Methods: In June 2021, 96 healthy male SD rats with SPF grade were divided into 1, 3, and 6-month control group and dust staining group (coal dust group, coal silica dust group, quartz group) according to random number table method, with 8 rats in each group. After one week of adaptive feeding, a one-time non-exposed tracheal perfusion method (1 ml/ piece) was used. The dust dyeing group was given 50 g/L coal dust, coal silica mixed dust and quartz dust suspension, respectively, and the control group was given 0.9% normal saline solution. At 1, 3 and 6 months after perfusion, lung function was detected by animal lung function apparatus, then all lung tissues and alveolar lavage fluid were killed, and lung histopathological morphological changes were observed by HE staining, and the contents of interleukin (IL-1β), IL-18, IL-4 and IL-10 in alveolar lavage fluid were detected by ELISA. One-way analysis of variance was used to compare groups. Two factors (inter-group treatment factor (4 levels) and observation time factor (3 levels) ) were used in the analysis of the effects of inter-group treatment and treatment time on related indicators. Results: HE staining results showed that coal spot appeared in the lung tissue of coal dust group, coal spot and coal silicon nodule appeared in the lung tissue of coal dust group, and silicon nodule appeared in the lung tissue of quartz group. Compared with the control group, the forced vital capacity (FVC) and forced expiratory volume at 0.2 second (FEV(0.2)) of rats in the dust staining group had interaction between the treatment and treatment time (P<0.05). With the increase of dust dyeing time, FVC and FEV(0.2) decreased significantly at 3-6 months of dust dyeing, and the maximum gas volume per minute (MVV) decreased significantly at 1-3 months of dust dyeing (P<0.05). The lowest lung function index was in quartz group, followed by coal-silica group and coal-dust group. There were statistically significant differences in the main effect and interaction effect of the pro-inflammatory factor IL-18 among all groups in treatment and treatment time (IL-18: F=70.79, 45.97, 5.90, P<0.001), and interaction existed. The highest content of inflammatory factors in alveolar lavage fluid of all dust groups was quartz group, followed by coal silica group and coal dust group. There were significant differences in the main effect and interaction effect of anti-inflammatory factors between groups and treatment time (IL-4: F=41.55, 33.01, 5.23, P<0.001, <0.001, <0.001; IL-10: F=7.46, 20.80, 2.91, P=0.002, <0.001, 0.024), and there was interaction. The highest content of anti-inflammatory factor was in quartz group, followed by coal silica group and coal dust group. Conclusion: Lung function decreased and levels of inflammatory fators increased in rat models of coal workers' pneumoconiosis, with the quartz group being the most severely damaged. Lung function is mainly impaired in thrid-six months, and the content of inflammatory factors begins to change in first-thrid months. MVV are the earliest and most obvious in lung function. IL-18 is suitable for monitoring changes in the pro-inflammatory response of coal workers' pneumoconiosis, and IL-10 is suitable for monitoring changes in anti-inflammatory response.

Mitigating effects of selenium and zinc on oxidative stress and biochemical and histopathological changes in lung during prenatal and lactational exposure rats to barium chloride.

Selenium (Se) and zinc (Zn) are essential trace elements with antioxidant properties, and their supplementation has been shown to be protective against the toxicity of various environmental and dietary substances. The aim of this study was to investigate the potential protective effect of selenium and zinc as adjuvants against barium (Ba) toxicity in lactating rats and their offspring. The pregnant rats were divided into six groups: the first as control; group 2 received barium (67ppm) in the drinking water; group 3 had combined Ba + Se (0.5mg/kg) in the diet; group 4 received Zn (50mg/kg bw) by gavage together with Ba; groups 5 and 6, positive controls, were treated with selenium (0.5mg/kg) and zinc (50mg/kg bw), respectively. MDA, H2O2, AOPP, CAT, GPx, and SOD levels were measured and lung histopathology was performed. Our results showed that barium administration caused lung damage as evidenced by an increase in MDA, H2O2, and AOPP levels and a decrease in the activities of CAT, GPx, and SOD in mothers and their offspring. A decrease in lung GSH, NPSH, and MT levels was also observed. Supplementation of Ba-treated rats with Se and/or Zn significantly improved the pulmonary antioxidant status of mothers and their offspring. Histopathological examinations were also consistent with the results of biochemical parameters, suggesting the beneficial role of Se and Zn supplementation, as evidenced by less accumulation of collagen fibers as studied by hematoxylin and eosin (H&E) and Masson's trichrome staining. In conclusion, we demonstrate the adverse effects of maternal barium exposure during pregnancy and on neonatal lung health and the protective effects of selenium and zinc in preventing the adverse effects of barium exposure.

Human angiotensin-converting enzyme 2–specific antisense oligonucleotides reduce infection with SARS-CoV-2 variants

BackgroundThe Spike protein mutation of SARS-CoV-2 led to decreased protective effect of various vaccines and monoclonal antibodies, suggesting that blocking SARS-CoV-2 infection by targeting host factors would make the therapy more resilient against virus mutations. Angiotensin converting enzyme 2 (ACE2) is the host receptor of SARS-CoV-2 and its variants, as well as many other coronaviruses. Down-regulation of ACE2 expression in the respiratory tract may prevent viral infection. Antisense oligonucleotides (ASOs) can be rationally designed based on sequence data, require no delivery system, and can be administered locally. ObjectiveWe sought to design ASOs that can block SARS-CoV-2 by down-regulating ACE2 in human airway. MethodsACE2-targeting ASOs were designed using a bioinformatic method and screened in cell lines. Human primary nasal epithelial cells cultured at the air-liquid interface and humanized ACE2 mice were used to detect the ACE2 reduction levels and the safety of ASOs. ASOs pretreated nasal epithelial cells and mice were infected and then used to detect the viral infection levels. ResultsASOs reduced ACE2 expression on mRNA and protein level in cell lines and in human nasal epithelial cells. Furthermore they efficiently suppressed virus replication of three different SARS-CoV-2 variants in human nasal epithelial cells. In vivo, ASOs also down-regulated human ACE2 in humanized ACE2 mice and thereby reduced viral load, histopathological changes in lungs, and they increased survival of mice. ConclusionACE2-targeting ASOs can effectively block SARS-COV-2 infection. Our study provides a new approach for blocking SARS-CoV-2 and other ACE2-targeting virus in high-risk populations.

Fermented Codonopsis lanceolata root extract exhibits anti-viral effects against influenza A infection by inhibiting neuraminidase activity and inflammatory responses

Codonopsis lanceolata, traditionally used in Asian herbal medicine to treat respiratory inflammation, contains various bioactive compounds, including saponins. The influenza A virus (IAV) is notorious for causing pandemics due to its ability to undergo antigenic shifts and drifts, complicating vaccine effectiveness and treatment approaches. This study investigates the protective and therapeutic effects of fermented C. lanceolata root extracts (FCLE) against IAV, comparing its efficacy with that of the original C. lanceolata root extracts (CLE) in both in vitro and in vivo models. FCLE demonstrated significantly higher antioxidant activity and an increased content of total polyphenols, saponins, and reducing sugars compared to CLE, although the content of lancemaside A was decreased in FCLE. FCLE also showed superior efficacy in reducing IAV-induced cytopathic effects and nucleocapsid protein expression in A549 cells, and virus titer in MDCK cells, particularly in post-treatment mode. However, CLE did not exhibit any protective effects against IAV infection. FCLE effectively inhibited neuraminidase (NA) activity and also tended to inhibit hemagglutinin. Furthermore, oral administration of FCLE at 100 mg/kg dramatically protected against lethal IAV infection, achieving a 100% survival rate, reducing virus titer, and ameliorating lung histopathological changes, with specific reductions in KC and IL-1β levels in bronchoalveolar lavage fluid (BALF). These results suggest that FCLE has considerable antiviral efficacy against IAV by both directly inhibiting viral replication via NA activity and orchestrating an antiviral immune response. Collectively, our findings indicate that FCLE could be a promising nutraceutical ingredient for respiratory health.

Histopathological study of lungs, kidney and spleen in death due to burns

Burn injuries occur universally and have plagued mankind ever since antiquity till the present day. As burns continue to be a major problem, a prospective study of demographic and pathological profile in deaths due to burns was conducted at the Department of Pathology Karnataka Institute of Medical Sciences Hubballi. To study the demographic profile, histopathological changes in lungs, kidney and spleen and to find the cause of death in cases due to burns. : The present study was carried out in the Department of Pathology, Karnataka institute of medical sciences, Hubballi, during the period of one year from 1-11-2014 to 31-10-2015. Total of 44 cases with burn injuries were used as material for study purpose and the collection of tissues were done for histopathology examination. This study includes 44 autopsy cases of death due to burn, of which majority were females. The age of the subjects ranged from 13 years to 65 years. Maximum numbers of victims were found in the age group of 21-30 years were 22 cases (50.00%).Most of the female victims were married and housewives. Most common manner of the burn were said accidental burns in 27 cases (61.36%) and 13 cases (29.54%) were due to suicidal burns, 4 cases (9.09%) were homicidal burns.Burns were more common in females most were married. Age group most commonly found was between 21-30 years of age probably related to dowry related issues, inexperience in cooking styles, house hold works, and inability to bear stress. Most common place of burns were kitchen. Most common manner of burns were said accidental. Most common cause of burns was due to said kerosene spill over or self pouring. TBSA involved more than 76%, in maximum number of cases. Maximum finding were seen in lung. Most common findings were diffuse alveolar damage, acute tubular injury and congested splenomegaly.

Histomorphological Spectrum of Lung Lesions in Medico- legal Autopsy in a Tertiary Care Centre

Background: Organ specific pathological changes seen during autopsy give a clear idea of the cause of death. Lungs are one of the most important vital organs in the human body. They are almost always involved in terminal events of cardiovascular diseases.Autopsy is important not only to know the state of lungs but also to study the morphology of various diseases.Various studies have demonstrated that,20-30% of sudden deaths are due to underlying pulmonary pathology. Aims and objectives: The significance of this study is to highlight the spectrum of histomorphological features of lung lesions in medico-legal autopsies irrespective of cause of death. Material and Methods:This was a retrospectivestudy Medico legal autopsies over a period of 5 years carried out in the Department of Pathology in coordination with the Department of Forensic Medicine, Gulbarga Institute of Medical Sciences. Standard protocols are used for gross and histopathology processing. Results: After thorough histopathological examination, of total 100 cases, various lesions were identified in 93 cases, in 7 cases tissue was autolyzed. Majority cases seen in the age group of 20-40yrs with male predominance. The most common cause of death was Road Traffic Accident (RTA) and majority victims were males. The commonly observed pathological features congestion and oedema(44.4%), Pneumonia(26.8%),CVC(22.2%) tuberculosis(9.6%) and ARDS(6.6%). Conclusion: The present study observed and documented histomorphological spectrum of lung lesions in medico-legal autopsies and highlighted various pathological conditions which are either direct or indirect cause of death. This study emphasizes that spectrum of histopathological changes in lungs of autopsy cases irrespective of cause of death and highlights some incidental interesting findings in lungs.

Insights into the mechanism of action of pterostilbene against influenza A virus-induced acute lung injury

BackgroundSevere respiratory system illness caused by influenza A virus infection is associated with excessive inflammation and abnormal apoptosis in alveolar epithelial cells (AEC). However, there are limited therapeutic options for influenza-associated lung inflammation and apoptosis. Pterostilbene (PTE, trans-3,5-dimethoxy-4-hydroxystilbene) is a dimethylated analog of resveratrol that has been reported to limit influenza A virus infection by promoting antiviral innate immunity, but has not been studied for its protective effects on virus-associated inflammation and injury in AEC. PurposeOur study aimed to investigate the protective effects and underlying mechanisms of PTE in modulating inflammation and apoptosis in AEC, as well as its effects on macrophage polarization during influenza virus infection. Study design and methodsA murine model of influenza A virus-mediated acute lung injury was established by intranasal inoculation with 5LD50 of mouse-adapted H1N1 viruses. Hematoxylin and eosin staining, immunofluorescence, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, western blotting, Luminex and flow cytometry were performed. ResultsPTE effectively mitigated lung histopathological changes and injury induced by H1N1 viruses in vivo. These beneficial effects of PTE were attributed to the suppression of inflammation and apoptosis in AEC, as well as the modulation of M1 macrophage polarization. Mechanistic investigations revealed that PTE activated the phosphorylated AMP-activated protein kinase alpha (P-AMPKα)/sirtui1 (Sirt1)/PPARγ coactivator 1-alpha (PGC1α) signal axis, leading to the inhibition of nuclear factor kappa-B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signaling induced by H1N1 viruses, thereby attenuating inflammation and apoptosis in AEC. PTE also forced activation of the P-AMPKα/Sirt1/PGC1α signal axis in RAW264.7 cells, counteracting the activation of phosphorylated signal transducer and activator of transcription 1 (P-STAT1) induced by H1N1 viruses and the augment of P-STAT1 activation in RAW264.7 cells with interferon-gamma (IFN-γ) pretreatment before viral infection, thereby reducing H1N1 virus-mediated M1 macrophage polarization as well as the enhancement of macrophages into M1 phenotypes elicited by IFN-γ pretreatment. Additionally, the promotion of the transition of macrophages towards the M2 phenotype by PTE was also related to activation of the P-AMPKα/Sirt1/PGC1α signal axis. Moreover, co-culturing non-infected AEC with H1N1 virus-infected RAW264.7 cells in the presence of PTE inhibited apoptosis and tight junction disruption, which was attributed to the suppression of pro-inflammatory mediators and pro-apoptotic factors in an AMPKα-dependent manner. ConclusionIn conclusion, our findings suggest that PTE may serve as a promising novel therapeutic option for treating influenza-associated lung injury. Its ability to suppress inflammation and apoptosis in AEC, modulate macrophage polarization, and preserve alveolar epithelial cell integrity highlights its potential as a therapeutic agent in influenza diseases.

Bone Marrow-Derived C-Kit+ Cells Improved Inflammatory IL-33/ST-2/ILC2 Axis in the Lung Tissue of Type 2 Diabetic Rats.

Inflammation is an essential factor in pulmonary complications of diabetes. Bone marrow (BM)-derived C-kit+ cells have immunomodulatory properties and their transplantation is suggested as a promising strategy for ameliorating diabetes complications. This study evaluated the effect of BM-derived C-kit+ cells on the inflammation signaling pathway in lung tissue of type 2 diabetic male rats. Ten rats were used to extract C-kit cells, and 48 male Wistar rats weighing 180 ± 20 g were randomly divided into four equal groups: (1) Control (Cont), (2) Diabetic (D), (3) Diabetic + C-kit+ cells (D + C-kit pos) intravenously injected 50-µl phosphate buffer saline (PBS) containing 300,000C-kit+ cells, and (4) Diabetic + C-kit- cells (D + C-kit neg), intravenously injected C-kit- cells. Diabetes induction increased IL-33, ST-2, CD127, and IL-2 levels and decreased IL-10. C-kit+ cell therapy significantly decreased IL-33 and CD127 and increased IL-10. In addition, lung histopathological changes significantly improved in the C-kit+ group compared to the diabetic group. These findings suggest that C-kit+ cells may have a potential therapeutic role in mitigating diabetes-induced respiratory complications via ameliorating the inflammation and histopathological changes in lung tissue.

Metabolomics combined with network pharmacology reveals anti-asthmatic effects of Nepeta bracteata on allergic asthma rats

ObjectiveTo investigate the mechanisms that underlie the anti-asthmatic effects of Nepeta bracteata (DBJJ, Dabao Jingjie in Chinese) in rats by integrating metabolomics and network pharmacology. MethodsIn this study, the rat model of asthma was induced by using ovalbumin (OVA), and subsequently, the rats were treated with a decoction of N. bracteata. Pathological changes in lung tissue were observed, and the quantification of eosinophils (EOS) and white blood cells (WBC) in bronchoalveolar lavage fluid (BALF) was performed. Furthermore, the serum levels of asthma-related factors induced by OVA were assessed. The proton nuclear magnetic resonance (1H NMR) spectroscopy serum metabolomics method was utilized to identify differential metabolites and their associated metabolic pathways. Moreover, UPLC-QE-MS/MS combined with network pharmacology was employed to predict the core targets and pathways of DBJJ in its action against asthma. Furthermore, the anti-asthmatic properties of DBJJ were investigated using an integrated approach of metabolomics and network pharmacology. Subsequently, the findings were validated through molecular docking and Western blotting analysis of the key targets. ResultsThe findings indicated that the administration of DBJJ effectively alleviated OVA-induced lung histopathological changes and decreased the number of EOS and WBC in BALF. Additionally, DBJJ inhibited the OVA-induced elevation of TNF-α, IL-18, Ig-E, EOS, IL-1β, MDA, VEGF-A, and TGF-β1. A total of 21 biomarkers and 10 pathways were found by metabolomics analysis. The 29 compounds were identified by UPLC-QE-MS/MS and 13 active components were screened by oral availability and Caco-2 cell permeability, the 120 targets and 173 KEGG pathways were predicted. The integration of metabolomics and network pharmacological analysis revealed that DBJJ's primary constituents, including ferulic acid and ursolic acid, exerted their effects on four targets, namely DAO and NOS2, as well as their associated metabolites and pathways. The active constituents of DBJJ demonstrated a high binding affinity towards DAO and NOS2. Furthermore, DBJJ was observed to decrease the protein expression and phosphorylation levels of NOS2, MAPK, and STAT3. ConclusionThe administration of DBJJ demonstrates notable anti-asthma properties in rats with allergic asthma. This effect can be attributed to the modulation of various targets, including NOS2, MAPK, and STAT3, by primary constituents such as ferulic acid and ursolic acid.

Akebia saponin D attenuates allergic airway inflammation through AMPK activation.

Akebia saponin D (ASD) is a bioactive triterpenoid saponin extracted from Dipsacus asper Wall. ex DC.. This study aimed to investigate the effects of ASD on allergic airway inflammation. Human lung epithelial BEAS-2B cells and bone marrow-derived mast cells (BMMCs) were pretreated with ASD (50, 100 and 200μΜ) and AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) (1mM), and then stimulated with lipopolysaccharide (LPS) or IL-33. Pretreatment with ASD and AICAR significantly inhibited TNF-α and IL-6 production from BEAS-2B cells, and IL-13 production from BMMCs. Moreover, pretreatment with ASD and AICAR significantly increased p-AMPK expression in BEAS-2B cells. Inhibition of AMPK by siRNA and compound C partly abrogated the suppression effect of ASD on TNF-α, IL-6, and IL-13 production. Asthma murine model was induced by ovalbumin (OVA) challenge and treated with ASD (150 and 300mg/kg) or AICAR (100mg/kg). Infiltration of eosinophils, neutrophils, monocytes, and lymphocytes, and production of TNF-α, IL-6, IL-4, and IL-13 were attenuated in ASD and AICAR treated mice. Lung histopathological changes were also ameliorated after ASD and AICAR treatment. Additionally, it showed that treatment with ASD and AICAR increased p-AMPK expression in the lung tissues. In conclusion, ASD exhibited protective effects on allergic airway inflammation through the induction of AMPK activation.

Crocin from saffron ameliorates allergic airway inflammation through NF-κB, IL-17, and Nrf2/HO-1 signaling pathways in mice.

Asthma is a complex inflammatory disorder with the infiltration of inflammatory cells in the lung airways. Saffron's active component, crocin, has been proven to possess anti-inflammatory and anti-oxidant effects. The objective of this current study was to explore the impact of crocin on NF-kB and nuclear erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) signaling pathways in ovalbumin (OVA)-sensitized mice, aiming to understand its mechanism. Four different groups were formed by dividing forty male BALB/C mice: control group, OVA-sensitized group (OVA), OVA combined with crocin 30 mg/kg (OVA-Cr30), and the OVA combined with crocin 60 mg/kg (OVA-Cr60). In order to determine the total number of WBC and inflammatory cells infiltrating the lung, we utilized the bronchoalveolar lavage fluid for counting purposes. The mRNA and protein levels of Nrf2, HO-1, IL-17, and NF-κB in lung tissue were assessed through real-time PCR and western blot techniques. Crocin significantly prevented the increase of total WBC and inflammatory cells in the lung tissue (P<0.001 for all) and histopathological changes in OVA-sensitized mice. Furthermore, crocin displayed suppressive effects on the enhancement of NF-kB (P<0.01) and IL-17 (P<0.05) mRNA and protein levels in OVA-sensitized mice while preserving Nrf2 (P<0.01) and HO-1 (P<0.05) expression levels. Crocin effects became increasingly apparent when utilized at high concentrations. Crocin decreased airway inflammation, partially by inhibiting NF-κB and IL-17 and up-regulating Nrf2/HO-1 mRNA and protein expression levels.

Exploring Lung Histopathology in White Rats After Cigarette Smoke Exposure

Smoking-induced respiratory epithelium changes, driven by nicotine and smoke components, can lead to severe lung alterations with prolonged exposure. However, until now, no one has examined the histopathological appearance of bronchioles and alveoli in Wistar rats following exposure to cigarette smoke. This study aimed to assessed lung histopathological changes in white rats (Rattus norvegicus) exposed to cigarette smoke. A descriptive study used a post-test group control design, exposing Rattus norvegicus to cigarette smoke and dividing them into control, 1-week, 2-week, and 4-week groups. Histopathological findings revealed that the control group had intact bronchioles; the one-week group showed lymphocyte infiltration and typical alveolar structure; the two-week group had increased respiratory epithelial cells; the four-week group displayed dominant bronchiole changes; the one-week group had varying alveolar septal thickness; the two-week group had narrowed alveolar lumens; four-week group showed thickened septa and pronounced pigmented macrophages. Cigarette smoke exposure affects changes to Rattus norvegicus lung histology. Prolonged exposure to cigarette smoke induces damage to the structure of the bronchioles and alveoli.

Protective Effects of Danmu Extract Syrup on Acute Lung Injury Induced by Lipopolysaccharide in Mice through Endothelial Barrier Repair.

To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.

Adipose tissue-derived mesenchymal stromal cells attenuate acute lung injury induced by trauma and haemorrhagic shock

BackgroundMesenchymal stromal cells (MSCs) have shown promising therapeutic options for acute lung injury (ALI) caused by multiple factors. Here, we evaluated the therapeutic potential of adipose tissue-derived mesenchymal stromal cells (ADSCs) in trauma and hemorrhagic shock (THS)-induced ALI. MethodsALI model induced by THS was constructed by fractures plus abdominal trauma plus acute hemorrhage plus fluid resuscitation. The ADSCs group rats were generated by injecting 2 × 106 ADSCs at 0 and 1 h after THS. The sham, ALI, and ADSCs group rats were sacrificed at 24 h after resuscitation. The changes in lung histopathology, total protein in bronchoalveolar lavage fluid (BALF), mRNA expression of pro-inflammatory/anti-inflammatory cytokines, antioxidant, and anti-apoptotic indicator, and the activity of Toll-like receptor 4 (TLR4) signaling in lung tissues were evaluated. ResultsAdministration of the ADSCs reversed ALI induced by THS, including lung histopathological changes/scores, and BALF total protein concentration. Additionally, ADSCs therapy also significantly down-regulated mRNA expression of pro-inflammatory TNF-α, IL-1β, and IL-6, up-regulated mRNA expression of anti-inflammatory IL-10, anti-apoptotic molecule Bcl-2, and anti-oxidative molecule HO-1 in THS rats. Furthermore, ADSCs suppressed the expression of TLR4 in lung tissue. ConclusionOur data show that ADSCs administration can exert therapeutic effects on THS-induced ALI in rats and may provide beneficial in preventative strategies for ALI.