Nicorandil mitigates arsenic trioxide-induced lung injury via modulating vital signalling pathways SIRT1/PGC-1α/TFAM, JAK1/STAT3, and miRNA-132 expression.

BACKGROUND AND PURPOSE: Nicorandil, a selective opener of potassium channels, used to treat angina, has drawn attention for its potential in mitigating lung injury, positioning it as a promising therapeutic approach to treat drug-induced lung toxicity. This study aimed to explore the protective role of nicorandil in arsenic trioxide (ATO)-induced lung injury and to elucidate the underlying mechanistic pathways. EXPERIMENTAL APPROACH: We assessed the effects of nicorandil (15 mg·kg-1, p.o.) in a rat model of pulmonary injury induced by ATO (5 mg·kg-1, i.p.). The assessment included oxidative stress biomarkers, inflammatory cytokine levels, and other biomarkers, including sirtuin-1, sirtuin-3, STAT3, TFAM, and JAK in lung tissue. Histological examination using H&E staining and molecular investigations using western blotting and PCR techniques were conducted. KEY RESULTS: In our model of lung injury, treatment with nicorandil ameliorated pathological changes as seen with H&E staining, reduced tissue levels of toxicity markers, and exerted significant antioxidant and anti-inflammatory actions. On a molecular level, treatment with nicorandil down-regulated JAK, STAT3, PPARγ, Nrf2, VEGF, p53, and micro-RNA 132 while up-regulating Sirt1, 3, TFAM, AMPK, and ERR-α in lung tissue. CONCLUSIONS AND IMPLICATIONS: The results presented here show nicorandil as a significant agent in attenuating lung injury induced by ATO in a rodent model. Nonetheless, further clinical studies are warranted to strengthen these findings.

Low-level PM2.5 induces the occurrence of early pulmonary injury by regulating circ_0092363.

The significant correlation between particulate matter with aerodynamic diameters of ≤ 2.5 µm (PM2.5) and the high morbidity and mortality of respiratory diseases has become the consensus of the research. Epidemiological studies have clearly pointed out that there is no safe concentration of PM2.5, and mechanism studies have also shown that exposure to PM2.5 will first cause pulmonary inflammation. Therefore, the purpose of this study is to explore the mechanism of early lung injury induced by low-level PM2.5 from the perspective of epigenetics. Based on the previous results of population samples, combined with an in vitro/vivo exposure model of PM2.5, it was found that low-level PM2.5 promoted the transport of circ_0092363 from intracellular to extracellular spaces. The decreased expression of intracellular circ_0092363 resulted in reduced absorption of miR-31-5p, leading to inhibition of Rho associated coiled-coil containing protein kinase 1 (ROCK1) and the subsequent abnormal expression of tight junction proteins such as Zonula occludens protein 1 (ZO-1) and Claudin-1, ultimately inducing the occurrence of early pulmonary injury. Furthermore, this study innovatively introduced organoid technology and conducted a preliminary exploration for a study of the relationship among environmental exposure genomics, epigenetics and disease genomics in organoids. The role of circ_0092363 in early pulmonary injury induced by low-level PM2.5 was elucidated, and its value as a potential diagnostic biomarker was confirmed.

In vitro and in vivo protective potential of quercetin-3-glucuronide against lipopolysaccharide-induced pulmonary injury through dual activation of nuclear factor-erythroid 2 related factor 2 and autophagy.

In vitro and in vivo models of lipopolysaccharide (LPS)-induced pulmonary injury, quercetin-3-glucuronide (Q3G) has been previously revealed the lung-protective potential via downregulation of inflammation, pyroptotic, and apoptotic cell death. However, the upstream signals mediating anti-pulmonary injury of Q3G have not yet been clarified. It has been reported that concerted dual activation of nuclear factor-erythroid 2 related factor 2 (Nrf2) and autophagy may prove to be a better treatment strategy in pulmonary injury. In this study, the effect of Q3G on antioxidant and autophagy were further investigated. Noncytotoxic doses of Q3G abolished the LPS-caused cell injury, and reactive oxygen species (ROS) generation with inductions in Nrf2-antioxidant signaling. Moreover, Q3G treatment repressed Nrf2 ubiquitination, and enhanced the association of Keap1 and p62 in the LPS-treated cells. Q3G also showed potential in inducing autophagy, as demonstrated by formation of acidic vesicular organelles (AVOs) and upregulation of autophagy factors. Next, the autolysosomes formation and cell survival were decreased by Q3G under pre-treatment with a lysosome inhibitor, chloroquine (CQ). Furthermore, mechanistic assays indicated that anti-pulmonary injury effects of Q3G might be mediated via Nrf2 signaling, as confirmed by the transfection of Nrf2 siRNA. Finally, Q3G significantly alleviated the development of pulmonary injury in vivo, which may result from inhibiting the LPS-induced lung dysfunction and edema. These findings emphasize a toxicological perspective, providing new insights into the mechanisms of Q3G's protective effects on LPS-induced pulmonary injury and highlighting its role in dual activating Nrf2 and autophagy pathways.

Lung-heart toxicity in a randomized clinical trial of hypofractionated image guided radiation therapy for breast cancer.

Background: TomoBreast hypothesized that hypofractionated 15 fractions/3 weeks image-guided radiation therapy (H-IGRT) can reduce lung-heart toxicity, as compared with normofractionated 25-33 fractions/5-7 weeks conventional radiation therapy (CRT). Methods: In a single center 123 women with stage I-II operated breast cancer were randomized to receive CRT (N=64) or H-IGRT (N=59). The primary endpoint used a composite four-items measure of the time to 10% alteration in any of patient-reported outcomes, physician clinical evaluation, echocardiography or lung function tests, analyzed by intention-to-treat. Results: At 12 years median follow-up, overall and disease-free survivals between randomized arms were comparable, while survival time free from alteration significantly improved with H-IGRT which showed a gain of restricted mean survival time of 1.46 years over CRT, P=0.041. Discussion: The finding establishes TomoBreast as a proof-of-concept that hypofractionated image-guided radiation-therapy can improve the sparing of lung-heart function in breast cancer adjuvant therapy without loss in disease-free survival. Hypofractionation is advantageous, conditional on using an advanced radiation technique. Multicenter validation may be warranted. Trial registration: https://clinicaltrials.gov/ct2/show/NCT00459628. Registered 12 April 2007.

Lias overexpression alleviates pulmonary injury induced by fine particulate matter in mice.

Oxidative stress and inflammation are mechanisms underlying toxicity induced by fine particulate matter (PM2.5). The antioxidant baseline of the human body modulates the intensity of oxidative stress in vivo. This present study aimed to evaluate the role of endogenous antioxidants in alleviating PM2.5-induced pulmonary injury using a novel mouse model (LiasH/H) with an endogenous antioxidant capacity of approximately 150% of its wild-type counterpart (Lias+/+). LiasH/H and wild-type (Lias+/+) mice were randomly divided into control and PM2.5 exposure groups (n = 10), respectively. Mice in the PM2.5 group and the control group were intratracheally instilled with PM2.5 suspension and saline, respectively, once a day for 7 consecutive days. The metal content, major pathological changes in the lung, and levels of oxidative stress and inflammation biomarkers were examined. The results showed that PM2.5 exposure induced oxidative stress in mice. Overexpression of the Lias gene significantly increased the antioxidant levels and decreased inflammatory responses induced by PM2.5. Further study found that LiasH/H mice exerted their antioxidant function by activating the ROS-p38MAPK-Nrf2 pathway. Therefore, the novel mouse model is useful for the elucidation of the mechanisms of pulmonary injury induced by PM2.5.

Intratracheally administered iron oxide nanoparticles induced murine lung inflammation depending on T cells and B cells.

Iron oxide nanoparticles (Fe2O3 NPs), produced in track traffic system and a wide range of industrial production, poses a great threat to human health. However, there is little research about the mechanism of Fe2O3 NPs toxicity on respiratory system. Rag1-/- mice which lack functional T and B cells were intratracheally challenged with Fe2O3 NPs, and interleukin (IL)-33 as an activator of group 2 innate lymphoid cells (ILC2s) to observe ILC2s changes. The lung inflammatory response to Fe2O3 NPs was alleviated in Rag1-/- mice compared with wild type (WT) mice. Infiltration of inflammatory cells and collagen deposition in tissue, leukocyte numbers (neutrophils, macrophages and lymphocytes), cytokine levels, such as IL-6, IL-13 and thymic stromal lymphopoietin (TSLP), and expression of Toll-like receptor (TLR)2, TLR4, and downstream myeloid differentiation factor (MyD)88, nuclear factor (NF)-κB and tumor necrosis factor (TNF)-α were decreased in lungs. Fe2O3 NPs markedly elevated ILC2s compared with the control, but ILC2s numbers were much lower compared with IL-33 in both WT and Rag1-/- mice. Furthermore, ILC2s amounts were strongly greater in Rag1-/- mice than WT mice. Our results suggested that Fe2O3 NPs induced sub-chronic pulmonary inflammation, which is majorly dependent on T cells and B cells rather than ILC2s.

Alanyl-Glutamine (Ala-Gln) Ameliorates Dextran Sulfate Sodium (DSS)-Induced Acute Colitis by Regulating the Gut Microbiota, PI3K-Akt/NF-κB/STAT3 Signaling, and Associated Pulmonary Injury.

The aim of this study was to investigate the protective effect of alanyl-glutamine (Ala-Gln) on acute colitis complicated by pulmonary injury induced by dextran sulfate sodium (DSS) in C57BL/6 mice. The results showed that Ala-Gln intervention alleviated weight loss, the disease activity index (DAI), colon shortening, and pathological injury and regulated the absolute number of CD4+T-cell subsets in mesenteric lymph nodes (MLNs). In addition, Ala-Gln intervention significantly ameliorated the composition of the gut microbiota in mice with DSS- induced acute colitis, significantly decreasing the relative abundance of Desulfovibrionaceae and increasing the abundances of Gastranaerophilales, Clostridia-vadinBB60, and Alistipes. Moreover, Ala-Gln treatment significantly inhibited the activation of the PI3K-Akt/NF-κB/STAT3 inflammatory signaling pathways in the colon of mice with DSS-induced acute colitis. Notably, Ala-Gln intervention also alleviated the pulmonary injury as well as the imbalance in levels of CD4+T-cell subsets in pulmonary tissue in mice with DSS-induced acute colitis. In conclusion, Ala-Gln alleviates DSS-induced acute colitis by regulating the gut microflora and PI3K-Akt/NF-κB/STAT3 signaling pathways, as well as by alleviating accompanying pulmonary injury.

Beneficial effect of the mitochondrial ATP­sensitive potassium channel­specific opener nicorandil on the collapsed lung via inhibition of apoptosis in clinical thoracic surgery.

With the use of thoracoscopic surgery technology, one­lung ventilation (OLV) is becoming more crucial as a basic requirement for enhanced recovery after surgery; however, it can lead to severe pulmonary injury, which is an issue for anesthesiologists. Therefore, it is important to protect pulmonary function during thoracic surgery anesthesia, particularly to protect the function of the collapsed lung. Our previous study on rabbits reported that nicorandil, a US Food and Drug Administration­approved mitochondrial ATP­sensitive potassium channel­specific opener, can protect against lung injury in the collapsed lung. Therefore, the beneficial effect of nicorandil on OLV­induced pulmonary injury in clinical thoracic surgery was further evaluated in the present study. Nicorandil was infused at 2 mg/h for 2 h from induction to 1 h after OLV in the nicorandil group. Trends in arterial oxygen desaturation (SaO2), arterial partial pressure for oxygen (PaO2) and the lung microstructure were assessed. ELISA was used to assess the levels of TNF­α and malondialdehyde (MDA), and the activity of superoxide dismutase (SOD). A TUNEL assay was performed to evaluate apoptosis. Western blotting was used to analyze the relative expression levels of signaling proteins associated with apoptosis. Western blotting was performed to evaluate the protein expression levels of hypoxia­inducible factor 1α (HIF­1α), PI3K, Akt and NF­κB, and reverse transcription­quantitative PCR was used to detect HIF­1α mRNA expression levels in the lungs of patients infused with nicorandil and nitroglycerin. Nicorandil treatment was associated with higher SaO2 and PaO2 compared with nitroglycerin treatment in OLV. The levels of MDA and TNF­α in the operated lung of the nicorandil group were significantly lower compared with those in the control group. In addition, nicorandil was associated with higher SOD activity compared with nitroglycerin. The nicorandil­treated lung, similar to the sham group, exhibited improved microstructure and less apoptosis in the experimental group. The protein expression levels of PI3K, phosphorylated Akt and HIF­1α were significantly increased, whereas NF­κB was significantly decreased in the nicorandil­treated lung compared with the control group. Overall, nicorandil demonstrated beneficial effects by decreasing apoptosis in the operated lung, which was collapsed and then re­expanded during OLV in thoracic surgery anesthesia. Nicorandil may serve a vital role by decreasing the overloading of calcium in mitochondria, shutting off the mitochondrial membrane permeability transition pore, reducing the release of cytochrome c, simultaneously triggering activation of the PI3K/Akt signaling pathway around the cell membrane, downregulating NF­κB, upregulating HIF­1α, and then reducing Bax/Bcl­2, caspase­3 and apoptosis. The trial registration was ChiCTR­IOR­17014061 (registered on December 20, 2017).

Lung ultrasonography versus chest CT for assessing peripheric pulmonary lesions in hemorrhagic fever with renal syndrome: a prospective comparative study in China.

OBJECTIVES: To compare the performances of lung ultrasonography (LUS) versus chest CT for assessing peripheric pulmonary lesions in hemorrhagic fever with renal syndrome (HFRS). METHODS: Paired LUS and chest CT scan were prospectively performed and compared when in diagnosing five pathologies including region with alveolar-interstitial pattern (RAIP), alveolar-interstitial syndrome (AIS), lung consolidation, pleural effusion (PE), and pericardial effusion, in each patient with HFRS. RESULTS: Forty-four patients (aged 39.9 ± 15.0 years, 35 males) were included, from which 68 paired LUS and chest CT imaging data of 816 lung regions were obtained and analyzed. Compared with chest CT, LUS showed high sensitivity (92.19-100%) and negative predictive value (95.9-100%), but relatively low specificity (39.47-97.21%) and positive predictive value (37.5-76.47%) for diagnosing the above pathologies. McNemer's test showed LUS detected more positive findings than chest CT (all p ≤ 0.002). There was a strong correlation between LUS and chest CT scores (rs = 0.7141, p < 0.0001) and both scores correlated with the disease severity, hospital days, and partial laboratory profiles in HFRS patients. CONCLUSIONS: LUS was comparable with chest CT for diagnosing peripheric pulmonary lesions and clinical assessment in patients with HFRS. Given the high sensitivity and negative predictive value compared with chest CT, LUS can be used as an excellent rule-out tool in HFRS, while its use in rule-in still requires more evidence. Considering the obvious advantages of LUS being a bedside, less expansive, and non-radiating exam, future multi-center randomized LUS versus chest CT studies may help to guide the preferred method. KEY POINTS: • LUS could detect more positive findings than chest CT in assessing peripheric pulmonary lesions in patients with hemorrhagic fever with renal syndrome (HFRS). • Compared with chest CT, LUS showed high sensitivity but relatively low specificity when diagnosing the peripheric pulmonary lesions caused by HFRS. • Both LUS and chest CT scores correlated with the disease severity, hospital days, and partial laboratory profiles in HFRS.

Pulmonary inflammation, oxidative stress, and fibrosis in a mouse model of cholestasis: the potential protective properties of the dipeptide carnosine.

Cholestasis is a clinical complication that primarily influences the liver. However, it is well known that many other organs could be affected by cholestasis. Lung tissue is a major organ influenced during cholestasis. Cholestasis-induced lung injury could induce severe complications such as respiratory distress, serious pulmonary infections, and tissue fibrosis. Unfortunately, there is no specific pharmacological intervention against this complication. Several studies revealed that oxidative stress and inflammatory response play a role in cholestasis-induced lung injury. Carnosine (CARN) is a dipeptide found at high concentrations in different tissues of humans. CARN's antioxidant and antiinflammatory properties are repeatedly mentioned in various experimental models. This study aimed to assess the role of CARN on cholestasis-induced lung injury. Rats underwent bile duct ligation (BDL) to induce cholestasis. Broncho-alveolar lavage fluid (BALF) levels of inflammatory cells, pro-inflammatory cytokines, and immunoglobulin were monitored at scheduled intervals (7, 14, and 28 days after BDL). Moreover, lung tissue histopathological alterations and biomarkers of oxidative stress were evaluated. A significant increase in BALF inflammatory cells, TNF-α, IL-1ß, IL-6, and immunoglobulin-G (IgG) was detected in the BALF of BDL rats. Moreover, lung tissue histopathological changes, collagen deposition, increased TGF-ß, and elevated levels of oxidative stress biomarkers were evident in cholestatic animals. It was found that CARN (100 and 500 mg/kg, i.p.) significantly alleviated lung oxidative stress biomarkers, inflammatory response, tissue fibrosis, and histopathological alterations. These data indicate the potential protective properties of CARN in the management of cholestasis-induced pulmonary damage. The effects of CARN on inflammatory response and oxidative stress biomarkers seems to play a crucial role in its protective properties in the lung of cholestatic animals.

Age-related exacerbation of lung damage after trauma is associated with increased expression of inflammasome components.

Background: Trauma, a significant global cause of mortality and disability, often leads to fractures and hemorrhagic shock, initiating an exaggerated inflammatory response, which harms distant organs, particularly the lungs. Elderly individuals are more vulnerable to immune dysregulation post-trauma, leading to heightened organ damage, infections, and poor health outcomes. This study investigates the role of NF-κB and inflammasomes in lung damage among aged mice post-trauma. Methods: Twelve male C57BL/6J mice underwent hemorrhagic shock and a femoral fracture (osteotomy) with external fixation (Fx) (trauma/hemorrhage, THFx), while another 12 underwent sham procedures. Mice from young (17-26 weeks) and aged (64-72 weeks) groups (n=6) were included. After 24h, lung injury was assessed by hematoxylin-eosin staining, prosurfactant protein C (SPC) levels, HMGB1, and Muc5ac qRT-PCR. Gene expression of Nlrp3 and Il-1ß, and protein levels of IL-6 and IL-1ß in lung tissue and bronchoalveolar lavage fluid were determined. Levels of lung-infiltrating polymorphonuclear leukocytes (PMNL) and activated caspase-3 expression to assess apoptosis, as well as NLRP3, ASC, and Gasdermin D (GSDMD) to assess the expression of inflammasome components were analyzed via immunostaining. To investigate the role of NF-κB signaling, protein expression of phosphorylated and non-phosphorylated p50 were determined by western blot. Results: Muc5ac, and SPC as lung protective proteins, significantly declined in THFx versus sham. THFx-aged exhibited significantly lower SPC and higher HMGB1 levels versus THFx-young. THFx significantly increased activated caspase-3 versus both sham groups, and THFx-aged had significantly more caspase-3 positive cells versus THFx-young. IL-6 significantly increased in both sham and THFx-aged groups versus corresponding young groups. THFx significantly enhanced PMNL in both groups versus corresponding sham groups. This increase was further heightened in THFx-aged versus THFx-young. Expression of p50 and phosphorylated p50 increased in all aged groups, and THFx-induced p50 phosphorylation significantly increased in THFx-aged versus THFx-young. THFx increased the expression of inflammasome markers IL-1ß, NLRP3, ASC and GSDMD versus sham, and aging further amplified these changes significantly. Conclusion: This study's findings suggest that the aging process exacerbates the excessive inflammatory response and damage to the lung following trauma. The underlying mechanisms are associated with enhanced activation of NF-κB and increased expression of inflammasome components.

Health effects and known pathology associated with the use of E-cigarettes.

In recent years, new nicotine delivery methods have emerged, and many users are choosing electronic cigarettes (e-cigarettes) over traditional tobacco cigarettes. E-cigarette use is very popular among adolescents, with more than 3.5 million currently using these products in the US. Despite the increased prevalence of e-cigarette use, there is limited knowledge regarding the health impact of e-cigarettes on the general population. Based on published findings by others, E-cigarette is associated with lung injury outbreak, which increased health and safety concerns related to consuming this product. Different components of e-cigarettes, including food-safe liquid solvents and flavorings, can cause health issues related to pneumonia, pulmonary injury, and bronchiolitis. In addition, e-cigarettes contain alarmingly high levels of carcinogens and toxicants that may have long-lasting effects on other organ systems, including the development of neurological manifestations, lung cancer, cardiovascular disorders, and tooth decay. Despite the well- documented potential for harm, e-cigarettes do not appear to increase susceptibility to SARS-CoV- 2 infection. Furthermore, some studies have found that e-cigarette users experience improvements in lung health and minimal adverse effects. Therefore, more studies are needed to provide a definitive conclusion on the long-term safety of e-cigarettes. The purpose of this review is to inform the readers about the possible health-risks associated with the use of e-cigarettes, especially among the group of young and young-adults, from a molecular biology point of view.

Angiotensin converting enzyme (ACE) inhibitors as radiation countermeasures for long-duration space flights.

Angiotensin converting enzyme (ACE) inhibitors are effective countermeasures to chronic radiation injuries in rodent models, and there is evidence for similar effects in humans. In rodent models ACE inhibitors are effective mitigators of radiation injury to kidney, lung, central nervous system (CNS) and skin, even when started weeks after irradiation. In humans, the best data for their efficacy as radiation countermeasures comes from retrospective studies of injuries in radiotherapy patients. We propose that ACE inhibitors, at doses approved for human use for other indications, could be used to reduce the risk of chronic radiation injuries from deep-space exploration. Because of the potential interaction of ACE inhibitors and microgravity (due to effects of ACE inhibitors on fluid balance) use might be restricted to post-exposure when/if radiation exposures reached a danger level. A major unresolved issue for this approach is the sparse evidence for the efficacy of ACE inhibitors after low-dose-rate exposure and/or for high-LET radiations (as would occur on long-duration space flights). A second issue is that the lack of a clear mechanism of action of the ACE inhibitors as mitigators makes obtaining an appropriate label under the Food and Drug Administration Animal Rule difficult.

Taurine mitigates the development of pulmonary inflammation, oxidative stress, and histopathological alterations in a rat model of bile duct ligation.

Lung injury is a significant complication associated with cholestasis/cirrhosis. This problem significantly increases the risk of cirrhosis-related morbidity and mortality. Hence, finding effective therapeutic options in this field has significant clinical value. Severe inflammation and oxidative stress are involved in the mechanism of cirrhosis-induced lung injury. Taurine (TAU) is an abundant amino acid with substantial anti-inflammatory and antioxidative properties. The current study was designed to evaluate the role of TAU in cholestasis-related lung injury. For this purpose, bile duct ligated (BDL) rats were treated with TAU (0.5 and 1% w: v in drinking water). Significant increases in the broncho-alveolar lavage fluid (BALF) level of inflammatory cells (lymphocytes, neutrophils, basophils, monocytes, and eosinophils), increased IgG, and TNF-α were detected in the BDL animals (14 and 28 days after the BDL surgery). Alveolar congestion, hemorrhage, and fibrosis were the dominant pulmonary histopathological changes in the BDL group. Significant increases in the pulmonary tissue biomarkers of oxidative stress, including reactive oxygen species formation, lipid peroxidation, increased oxidized glutathione levels, and decreased reduced glutathione, were also detected in the BDL rats. Moreover, significant myeloperoxidase activity and nitric oxide levels were seen in the lung of BDL rats. It was found that TAU significantly blunted inflammation, alleviated oxidative stress, and mitigated lung histopathological changes in BDL animals. These data suggest TAU as a potential protective agent against cholestasis/cirrhosis-related lung injury.

Multi-omics analysis unravels dysregulated lysosomal function and lipid metabolism involved in sub-chronic particulate matter-induced pulmonary injury.

Particulate matter (PM) is a huge environmental threat and is of major public concern. Oxidative stress and systemic inflammation are known factors that contribute to PM- related damage; however, a systematic understanding of the deleterious pulmonary effects of PM using multi-omics analysis is lacking. In this study, we performed transcriptomic, proteomic, and metabolomic analyses in a mouse model exposed to PM for three months to identify molecular changes in lung tissues. We identified 1690 genes, 326 proteins, and 67 metabolites exhibiting significant differences between PM-challenged and control mice (p < 0.05). Differentially expressed genes and proteins regulated in PM-challenged mice were involved in lipid metabolism and in the immune and inflammatory response processes. Moreover, a comprehensive analysis of transcript, protein, and metabolite datasets revealed that the genes, proteins, and metabolites in the PM-treated group were involved in lysosomal function and lipid metabolism. Specifically, Cathepsin D (Ctsd), Ferritin light chain (Ftl), Lactotransferrin (Ltf), Lipocalin 2 (Lcn2), and Prosaposin (Psap) were major proteins/genes associated with PM-induced pulmonary damage, while two lipid molecules PC (18:1(11Z)/16:0) and PA (16:0/18:1(11Z)) were major metabolites related to PM-induced pulmonary injury. In summary, lipid metabolism might be used as successful precautions and therapeutic targets in PM-induced pulmonary injury to maintain the stability of cellular lysosomal function.

Successful treatment of pulmonary injury due to nitrogen oxide exposure with extracorporeal membrane oxygenation: a report of two cases and literature review.

Background: Severe nitrogen oxide poisoning can lead to life-threatening pulmonary injury.Methods: we report two cases of severe nitrogen-oxide-induced hypoxia treated with veno-venous extracorporeal membrane oxygenation (ECMO). After exposure, the conditions of both patients continued to deteriorate despite maximal mechanical ventilation with a fraction of inspired oxygen of 100%; therefore, we started veno-venous ECMO. The times from presentation to the initiation of ECMO in the two patients were 1 and 2 days. The hypoxemia and respiratory failure improved quickly after ECMO support.Results: The patients were discharged without complications. The durations of ECMO for the two patients were 5 and 6 days. Conclusion: This report describes how early ECMO support was used to treat potentially fatal pulmonary injury after exposure to nitrogen oxide. The duration of the ECMO run is a critical determinant of patient survival.

A Comprehensive Review of Vaping Use in Pediatric Patients and Recent Changes in Regulatory Laws.

The use of electronic cigarettes (e-cigarettes), also known as vapes, by adolescents and young adults has dramatically increased over the past several years. E-cigarettes continue to be the most used form of tobacco among youth. As a result of this concerning trend, policies at both the state and federal levels have been implemented to limit availability in this population. Additionally, the coronavirus disease 2019 (COVID-19) pandemic has had some positive and negative effects on the youth vaping epidemic with adolescent consumers reporting limited access to retail sites during the stay-at-home executive orders, but easier access with online purchasing because age verification was often not required. Complications resulting from vaping have been reported and include e-cigarette or vaping product use-associated lung injury (EVALI) and thrombotic events. Data suggest that the use of vaping devices can lead to both short- and long-term respiratory morbidity in the pediatric population. This review serves to provide a comprehensive examination of vaping use in pediatric patients and recent changes in regulatory laws to equip pharmacists with the knowledge to be aware of the different devices and products available, ask their pediatric patients regularly about use, and counsel and educate on the potential harmful effects.

Characteristics of Adults Who Use Both Marijuana and E-Cigarette, or Vaping, Products: A Cross-Sectional Study, Utah, 2018.

OBJECTIVES: Among young people, dual use of marijuana and e-cigarette, or vaping, products (EVPs) is linked with using more inhalant substances and other substances, and poorer mental health. To understand antecedents and potential risks of dual use in adults, we analyzed a representative adult population in Utah. METHODS: We used data from the 2018 Utah Behavioral Risk Factor Surveillance System (n = 10 380) and multivariable logistic regression to evaluate differences in sociodemographic characteristics, comorbidities, and risk factors among adults aged ≥18 who reported currently using both EVPs (any substance) and marijuana (any intake mode), compared with a referent group of adults who used either or neither. RESULTS: Compared with the referent group, adults using EVPs and marijuana had greater odds of being aged 18-29 (adjusted odds ratio [aOR] = 12.44; 95% CI, 6.15-25.14) or 30-39 (aOR = 3.75; 95% CI, 1.73-8.12) versus ≥40, being male (aOR = 3.29; 95% CI, 1.82-5.96) versus female, reporting ≥14 days of poor mental health in previous 30 days (aOR = 2.30; 95% CI, 1.23-4.32) versus <14 days, and reporting asthma (aOR = 2.09; 95% CI, 1.02-4.31), chronic obstructive pulmonary disorder (aOR = 2.94; 95% CI, 1.19-7.93), currently smoking cigarettes (aOR = 4.56; 95% CI, 2.63-7.93), or past-year use of prescribed chronic pain medications (aOR = 2.13; 95% CI, 1.06-4.30), all versus not. CONCLUSIONS: Clinicians and health promotion specialists working with adults using both EVPs and marijuana should assess risk factors and comorbidities that could contribute to dual use or associated outcomes and tailor prevention messaging accordingly.

Lycopene hampers lung injury due to skeletal muscle ischemia-reperfusion in rat model.

This study investigates lycopene's preventive efficacy in skeletal muscle ischemia-reperfusion (I/R) induced lung injury. Thirty-two rats were randomly assigned to control group, lycopene group, I/R group and I/R + lycopene group. In the lycopene and I/R + lycopene groups, the rats initially received 10 mg/kg/day lycopene orally for 15 days. Then, dissection around the abdominal aorta was performed in all rats under general anesthesia. The aorta was clamped at the infrarenal level in the I/R group and I/R + lycopene group for two hours before two hours of reperfusion. The mean serum levels of malondialdehyde (53.0 ± 20.14 nmol/mL) and superoxide dismutase (1.03 ± 0.16 U/mL) were higher and lower in the I/R group than the other three groups, respectively (p < 0.001). The mean serum IMA level of I/R + lycopene group (0.42 ± 0.04 abs/u) was lower than the I/R group (0.47 ± 0.04 abs/u) (p = 0.015). The mean tissue malondialdehyde levels of I/R group (69.10 ± 11.55 nmol/mL) and I/R + lycopene group (68.36 ± 21.17 nmol/mL) were high compared to the control group (49.87 ± 6.52 nmol/mL) and lycopene group (47.82 ± 4.44 nmol/mL) (p = 0.002). The mean tissue glutathione peroxidase (p < 0.001) and superoxide dismutase (p = 0.001) levels of I/R group (121.81 ± 43.59 nmol/mL and 25.17 ± 8.69 U/mL) were low compared to the control group (236.12 ± 18.01 nmol/mL and 46.30 ± 5.17 U/mL), lycopene group (227.52 ± 16.92 nmol/mL and 45.82 ± 4.02 U/mL), and I/R + lycopene group (176.02 ± 24.27 nmol/mL and 35.20 ± 4.85 U/mL). The histopathological analyses of I/R + lycopene group indicated less significant changes than the control group. Tissue damage in the I/R + lycopene group was less prominent than the I/R group. These findings suggest oral lycopene supplementation as a promising prevention against skeletal muscle I/R caused lung injury.

Exploring the potential neurotoxicity of vaping vitamin E or vitamin E acetate.

Serious adverse health effects have been reported with the use of vaping products, including neurologic disorders and e-cigarette or vaping product use-associated lung injury (EVALI). Vitamin E acetate, likely added as a diluent to cannabis-containing products, was linked to EVALI. Literature searches were performed on vitamin E and vitamin E acetate-associated neurotoxicity. Blood brain barrier (BBB) penetration potential of vitamin E and vitamin E acetate were evaluated using cheminformatic techniques. Review of the literature showed that the neurotoxic potential of inhalation exposures to these compounds in humans is unknown. Physico-chemical properties demonstrate these compounds are lipophilic, and molecular weights indicate vitamin E and vitamin E acetate have the potential for BBB permeability. Computational models also predict both compounds may cross the BBB via passive diffusion. Based on literature search, no experimental nonclinical studies and clinical information on the neurotoxic potential of vitamin E via inhalation. Neurotoxic effects from pyrolysis by-product, phenyl acetate, structurally analogous to vitamin E acetate, suggests vitamin E acetate has potential for central nervous system (CNS) impairment. Cheminformatic model predictions provide a theoretical basis for potential CNS permeability of these inhaled dietary ingredients suggesting prioritization to evaluate for potential hazard to the CNS.