We aimed to evaluate the effects of seven weeks of aerobic exercise training and piperine on paraquat-induced lung damage. Forty-eight male Wistar rats (230 g, six-eight weeks old) were randomly divided into six groups (n = 8): sham, paraquat (5 mg/kg three times a week; intraperitoneally), paraquat + piperine (10 mg/kg/day; orally), paraquat + aerobic exercise training, paraquat + piperine + aerobic exercise training; and paraquat + vitamin E (20 mg/kg/day; orally) as a positive control. Rats were sacrificed on day 50, and both lung tissues were isolated to measure oxidative (MDA), anti-oxidative (GSH), inflammatory (TNF-α), anti-inflammatory (IL-10) markers, and histological evaluations (hematoxylin-eosin staining). The results of the present study revealed that paraquat significantly decreased body weight, GSH, GSH/MDA ratio, IL-10, and IL-10/TNF-α ratio while increasing MDA, TNF-α, and histopathological damage in lung tissue (P < 0.01 to 0.001). In contrast, treatment with all four interventions meaningfully diminished oxidative, inflammatory markers, and histopathological damage while propagating body weight, anti-oxidative and anti-inflammatory markers following the paraquat-induced lung damage (P < 0.05 to P < 0.001). Interestingly, piperine and piperine + exercise training possessed stronger protective effects against paraquat-induced lung damage than exercise training alone (P < 0.01 to 0.001). Treatment with piperine, exercise training, piperine + exercise training, and vitamin E significantly ameliorated paraquat-induced lung damage. Interestingly, the piperine and piperine + exercise training had more protective effects than other groups. Therefore, piperine and the combination of piperine and exercise training may be valuable candidates for preventing lung injuries.

Injury to internal organs caused by myocardial infarction (MI), although often neglected, is a very serious condition which damages internal organs especially the lungs. Changes in microcirculation can begin with acute lung injury and result in severe respiratory failure. The aim of this study was to create new approaches that will explain the pathophysiology and treatment of the disease by examining the therapeutic effects of vitamin D (VITD) and Nerolidol (NRD) on the injuries of the lungs caused by MI, and their relationship with asprosin / spexin proteins.
METHODS: Six groups of seven experimental animals each were constituted. Control, VITD (only 50 IU/day during the experiment), NRD (only 100 mg/kg/day during the experiment), MI (200 mg/kg isoproterenol was administered to rats as a single dose subcutaneously), MI+VITD (200 mg/kg isoproterenol +50 IU/day) and MI+NRD (200 mg/kg isoproterenol +100 mg/kg/day) were the six (6) groups constituted. Tissues were analyzed using histopathological and immunohistochemical methods, whereas serum samples were analyzed using ELISA method.
RESULTS: The result of the histopathological study for the MI group showed an observed increase in inflammatory cells, congestion, interalveolar septal thickening, erythrocyteloaded macrophages and fibrosis in the lung tissues. The treatment groups however recorded significant differences with regards to these parameters. In the immunohistochemical analysis, expressions of asprosin and spexin were observed in the smooth muscle structures and interalveolar areas of the vessels and bronchioles of the lung, as well as the bronchiole epithelium. There was no significant difference between the groups in terms of asprosin and spexin expression in the bronchiol epithelium. When immunohistochemical and serum ELISA results were examined, it was observed that asprosin levels increased significantly in the lung tissues of the MI group compared to the control group, decreased significantly in the treatment groups treated with Vitamin D and NRD after MI. While spexin decreased significantly in the MI group compared to the control group, it increased significantly in the MI+VİTD group, but did not change in the MI+NRD group.
CONCLUSIONS: It was observed that serious injuries occurred in the lungs due to myocardial infarction and that, VITD and NRD treatments had a curative effect on those injuries. It was also observed that Asprosin and Speksin proteins can have effect on mechanisms of both injury and therapy of the lung. Furthermore, the curative effects of VITD are dependent on the expression of asprosin and spexin; whereas the observation indicated that nerolidol could be effective through asprosin-dependent mechanisms and specisin by independent mechanisms.

Recent studies suggested the potential role of mast cells (MCs) in the pathology of coronavirus disease 2019 (COVID-19). However, the precise description of the MCs\' activation and the engagement of their proteases is still missing. The objective of this study was to further reveal the importance of MCs and their proteases (chymase, tryptase, and carboxypeptidase A3 (CPA3)) in the development of lung damage in patients with COVID-19. This study included 55 patients who died from COVID-19 and 30 controls who died from external causes. A histological analysis of the lung parenchyma was carried out to assess the protease profiles and degranulation activity of MCs. In addition, we have analyzed the general blood test, coagulogram, and C-reactive protein. The content of tryptase-positive MCs (Try-MCs) in the lungs of patients with COVID-19 was higher than in controls, but their degranulation activity was lower. The indicators of chymase-positive MCs (Chy-MCs) were significantly lower than in the controls, while the content of CPA3-positive MCs (CPA3-MCs) and their degranulation activity were higher in patients with COVID-19. In addition, we have demonstrated the existence of correlations (positive/negative) between the content of Try-MCs, Chy-MCs, and CPA3-MCs at different states of their degranulation and presence (co-adjacent/single) and the levels of various immune cells (neutrophils, eosinophils, basophils, and monocytes) and other important markers (blood hemoglobin, activated partial thromboplastin time (aPTT), international normalized ratio (INR), and fibrinogen). Thus, the identified patterns suggest the numerous and diverse mechanisms of the participation of MCs and their proteases in the pathogenesis of COVID-19, and their impact on the inflammatory process and coagulation status. At the same time, the issue requires further study in larger cohorts of patients, which will open up the possibility of using drugs acting on this link of pathogenesis to treat lung damage in patients with COVID-19.

Influenza virus infection is a worldwide challenge that causes heavy burdens on public health. The mortality rate of severe influenza patients is often associated with hyperactive immunological abnormalities characterized by hypercytokinemia. Due to the continuous mutations and the occurrence of drug-resistant influenza virus strains, the development of host-directed immunoregulatory drugs is urgently required. Platycodon grandiflorum is among the top 10 herbs of traditional Chinese medicine used to treat pulmonary diseases. As one of the major terpenoid saponins extracted from Platycodon grandiflorum, Platycodin D (PD) has been reported to play several roles, including anti-inflammation, analgesia, anti-cancer, hepatoprotection, and immunoregulation. However, the therapeutic roles of PD to treat influenza virus infection remains unknown. Here, we show that PD can protect the body weight loss in severely infected influenza mice, alleviate lung damage, and thus improve the survival rate. More specifically, PD protects flu mice via decreasing the immune cell infiltration into lungs and downregulating the overactivated inflammatory response. Western blot and immunofluorescence assays exhibited that PD could inhibit the activation of TAK1/IKK/NF-κB and MAPK pathways. Besides that, CETSA, SPR and immunoprecipitation assays indicated that PD binds with TRAF6 to decrease its K63 ubiquitination after R837 stimulation. Additionally, siRNA interference experiments exhibited that PD could inhibit the secretion of IL-1β and TNF-α in TRAF6-dependent manner. Altogether, our results suggested that PD is a promising drug candidate for treating influenza. Our study also offered a scientific explanation for the commonly used Platycodon grandiflorum in many anti-epidemic classic formulas. Due to its host-directed regulatory role, PD may serve as an adjuvant therapeutic drug in conjunction with other antiviral drugs to treat the flu.

Rationale: Particulate matter (PM) exposure exacerbates health outcomes by causing lung damage. Objectives: To investigate whether prior exposure to particulate matter ⩽10 μm and ⩽2.5 μm in aerodynamic diameter (PM10 and PM2.5) was associated with clinical outcomes among patients with coronavirus disease (COVID-19). Methods: Data from the nationwide registration database of the National Health Insurance and Korea Disease Control and Prevention Agency in South Korea were used. The study included adult patients who were admitted to monitoring centers or hospitals between October 8, 2020 and December 31, 2021, after COVID-19 confirmation. AirKOREA database, which compiles air pollutant data from 642 stations in 162 cities and counties across South Korea, was used to extract data on PM levels. Average values of monthly exposure to PM10 and PM2.5 from the year previous to hospital admission because of COVID-19 to the date of confirmation of COVID-19 were calculated and used to define PM exposures of patients with COVID-19. Results: In total, 322,289 patients with COVID-19 were included, and 4,633 (1.4%) died during hospitalization. After adjusting for covariates, a 1-μg/m3 increase in PM10 and PM2.5 exposure was associated with 4% (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.03-1.05; P < 0.001) and 6% (OR, 1.06; 95% CI, 1.04-1.07; P < 0.001) increase in the risk of in-hospital mortality, respectively. In addition, a 1-μg/m3 increase in PM10 and PM2.5 was associated with 5% (OR, 1.05; 95% CI, 1.04-1.07; P < 0.001) and 8% (OR, 1.08; 95% CI, 1.06-1.10; P < 0.001) increase in the risks of requiring intensive care unit (ICU) admission and mechanical ventilation, respectively. Conclusions: PM10 and PM2.5 exposure was associated with increased in-hospital mortality and the need for ICU admission and mechanical ventilation among patients with COVID-19 in South Korea.

The adverse effects of exposure to fine particulate matter (PM2.5) on body health have attracted global public attention. However, there is limited research on PM2.5 in animal houses. Numerous studies have indicated that long-term exposure to high levels of PM2.5 can cause damage to multiple systems in animals. Poultry houses are one of the primary sources of PM2.5 emissions. However, there is limited research on the effects of PM2.5 exposure on poultry organisms. This study analyzed the histopathological changes in the lung tissue of poultry under PM2.5 exposure conditions. It used the LC-MS method to analyze the alterations in the serum metabolomic profile of poultry. This study confirmed that long-term exposure to high levels of PM2.5 had significantly reduced the growth performance of poultry. Histopathological slides of the lung tissue in chickens exposed to long-term retention of PM2.5 clearly showed significant damage. Furthermore, the serum metabolome analysis revealed significant changes in the serum metabolic profile of chickens exposed to long-term PM2.5 exposure. Specifically, there were notable alterations in the Glycerophospholipid metabolism, Steroid hormone biosynthesis, and Phenylalanine, tyrosine, and tryptophan biosynthesis pathways.

CD4+ T cells are key components of the immune response during lung infections and can mediate protection against tuberculosis (TB) or influenza. However, CD4+ T cells can also promote lung pathology during these infections, making it unclear how these cells control such discrepant effects. Using mouse models of hypervirulent TB and influenza, we observe that exaggerated accumulation of parenchymal CD4+ T cells promotes lung damage. Low numbers of lung CD4+ T cells, in contrast, are sufficient to protect against hypervirulent TB. In both situations, lung CD4+ T cell accumulation is mediated by CD4+ T cell-specific expression of the extracellular ATP (eATP) receptor P2RX7. P2RX7 upregulation in lung CD4+ T cells promotes expression of the chemokine receptor CXCR3, favoring parenchymal CD4+ T cell accumulation. Our findings suggest that direct sensing of lung eATP by CD4+ T cells is critical to induce tissue CD4+ T cell accumulation and pathology during lung infections.

BACKGROUND: Due to the relatively short existence of alternative tobacco products, gaps exist in our current understanding of their long-term respiratory health effects. We therefore undertook the first-ever side-by-side comparison of the impact of chronic inhalation of aerosols emitted from electronic cigarettes (EC) and heated tobacco products (HTP), and combustible cigarettes (CC) smoke.
OBJECTIVE: To evaluate the potential differential effects of alternative tobacco products on lung inflammatory responses and efficacy of vaccination in comparison to CC.
METHODS: Mice were exposed to emissions from EC, HTP, CC, or air for 8 weeks. BAL and lung tissue were analyzed for markers of inflammation, lung damage, and oxidative stress. Another group was exposed for 12 weeks and vaccinated and challenged with a bacterial respiratory infection. Antibody titers in BAL and sera and pulmonary bacterial clearance were assessed.
RESULTS: EC- and HTP-aerosols significantly augmented lung immune cell infiltrates equivalent to that achieved following CC-exposure. HTP and CC significantly increased neutrophil numbers compared to EC. All products augmented numbers of B cells, T cells, and pro-inflammatory IL17A+ T cells in the lungs. Decreased lung antioxidant activity and lung epithelial and endothelial damage was induced by all products. EC and HTP differentially augmented inflammatory cytokines/chemokines in the BAL. Generation of immunity following vaccination was impaired by EC and HTP but to a lesser extent than CC, with a CC > HTP > EC hierarchy of suppression of pulmonary bacterial clearance.
CONCLUSIONS: HTP and EC-aerosols induced a proinflammatory pulmonary microenvironment, lung damage, and suppressed efficacy of vaccination.

The objective of this study was to explore the effects of antioxidant treatments, specifically N-acetylcysteine (NAC) and N-acetylcysteine amide (NACA), in a mouse model of chlorine (Cl2)-induced lung injury. Additionally, the study aimed to investigate the utility of pig precision-cut lung slices (PCLS) as an ex vivo alternative for studying the short-term effects of Cl2 exposure and evaluating antioxidant treatments. The toxicological responses were analyzed in Cl2-exposed mice (inflammation, airway hyperresponsiveness (AHR)) and PCLS (viability, cytotoxicity, inflammatory mediators). Airways contractions were assessed using a small ventilator for mice and electric-field stimulation (EFS) for PCLS. Antioxidant treatments were administered to evaluate their effects. In Cl2-exposed mice, NAC treatment did not alleviate AHR, but it did reduce the number of neutrophils in bronchoalveolar lavage fluid and inflammatory mediators in lung tissue. In PCLS, exposure to Cl2 resulted in concentration-dependent toxicity, impairing the lung tissue\'s ability to respond to EFS-stimulation. NAC treatment increased viability, mitigated the toxic responses caused by Cl2 exposure, and maintained contractility comparable to unexposed controls. Interestingly, NACA did not provide any additional treatment effect beyond NAC in both models. In conclusion, the establishment of a pig model for Cl2-induced lung damage supports further investigation of NAC as a potential treatment. However, the lack of protective effects on AHR after NAC treatment in mice suggests that NAC alone may not be sufficient as a complete treatment for Cl2 injuries. Optimization of existing medications with a polypharmacy approach may be more successful in addressing the complex sequelae of Cl2-induced lung injury.

UNASSIGNED: Smoking is the leading cause of death in worldwide and is known as one of the risk factors in the development and pathogenesis of several diseases and most are respiratory and cardiovascular diseases. Secondhand smoke (SHS) exposure is associated with negative health consequences including respiratory tract infection, asthma, and cancer. One of the pathogenesis that has known to cause these diseases is inflammation. Garlic (Allium sativum) is a medicinal herb that contains Allicin and other active constituents that are known to have anti-inflammatory ability by suppressing the expression and production of proinflammatory cytokines that will cause inflammation.
UNASSIGNED: The aim of this study is; to analyze the anti-inflammatory action of Allium sativum ethanol extract to prevent lung damage in the smoker rat model.
UNASSIGNED: This is a case-control study with five groups of rats each group contains of three rats. The five groups were negative control (KN), 10 days (10d) smoker (K1), 20 days (20d) smoker (K2), 20d smoker treated with Allium sativum for 10 days (K3) and 20d smoker treated with Allium sativum for 20 days (K4). After 20 days all animals were sacrificed and histological preparation of lung organs was observed under a microscope with 100 dan 400 times magnification and then captured by photomicrograph for analyzed.
UNASSIGNED: There were improvements in lung structure both in group K3 and K4 . there was a decrease of leucocytes and inflammatory cells infiltration that covered almost all alveolar surface to 10-20% surface area and the dilated alveoli decrease from more than 50% to less than 30% area. The bronchus was clean in both two groups compared to the groups that were not treated with Allium sativum.
UNASSIGNED: This study shows that Allium sativum ethanol extract has the ability to prevent lung damage in the smoker rat model.