scholarly journals Bixin protects against particle-induced long-term lung injury in an NRF2-dependent manner

2018 ◽  
Vol 7 (2) ◽  
pp. 258-270 ◽  
Author(s):  
Lian Xue ◽  
Hong Zhang ◽  
Jie Zhang ◽  
Bingyan Li ◽  
Zengli Zhang ◽  
...  
Keyword(s):  
Lung Injury ◽  
Pulmonary Disease ◽  
Dependent Manner

Scope: Particle-induced lung injury is a kind of comprehensive pulmonary disease with not only inflammation but also fibrosis.

scholarly journals What is a Therapeutic Potential of N-Acetylcysteine in Lung Silicosis?

2021 ◽  
Vol 21 (3) ◽  
pp. 80-89
Author(s):  
Adamcakova Jana ◽  
Mokra Daniela
Keyword(s):  
Oxidative Stress ◽  
Lung Injury ◽  
Silicon Dioxide ◽  
Pulmonary Disease ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Clinical Use ◽  
Fundamental Factor ◽  
Long Term Experience

Abstract Lung silicosis is a serious pulmonary disease caused by an exposure of lung to inhaled silicon dioxide (SiO2) or silica. Although pathomechanisms of the disease have not been fully elucidated, oxidative stress has been recognized as a fundamental factor triggering a fibrotizing inflammation leading to irreversible changes in lung tissue. Based on this knowledge, therapeutic potential of various antioxidants has been intensively discussed. Among them, N-acetylcysteine with its multiple anti-inflammatory and antioxidant actions and a long-term experience with its clinical use in various diseases appears as a very promising choice. The purpose of this article is to review the therapeutic effects of N-acetylcysteine particularly in relation to a lung injury and to point out a potential of N-acetylcysteine in the treatment of lung silicosis.

17 Long-Term Pulmonary Sequelae After Inhalation Injury: A Retrospective Cohort Study

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S17-S17
Author(s):  
Julian Wier ◽  
Ian F Hulsebos ◽  
Haig A Yenikomshian ◽  
Justin Gillenwater
Keyword(s):  
Pulmonary Disease ◽  
Multinomial Logistic Regression ◽  
Smoking Status ◽  
Group Versus ◽  
Inhalation Injury ◽  
Primary Study ◽  
Burn Patients ◽  
Post Discharge ◽  
Ventilated Patients

Abstract Introduction Inhalation injury (INHI) has strong associations with increased rates of in-patient mortality and pneumonia. Data describing long-term health outcomes after inhalation injury are scarce and the true sequelae are largely unknown. The aim of the study is to review long-term pulmonary outcomes in inhalation injury patients. We hypothesize that INHI patients are at greater risk of developing long-term pulmonary sequelae. Methods We present a retrospective case-control of burn patients admitted to an ABA certified facility. We included burn patients with or without medically confirmed INHI who were admitted between 06/2016 to 11/2019 and were part of the regional Department of Health Services (DHS) system. The experimental group was patients with bronchoscopy confirmed INHI. The control groups were ventilated patients with confirmed non-inhalation injury (V) and non-ventilated patients with confirmed non-inhalation injury (NV). These were matched for age, TBSA, sex, previous comorbid pulmonary disease, and smoking status. Primary study outcomes were rates of post-discharge pulmonary sequelae, including ineffective airway clearance, infections, shortness of breath, and malignancy. Secondary outcomes included rates of post-discharge surgeries and readmission, post-discharge non-pulmonary sequelae, and post-discharge days to pulmonary/non-pulmonary sequelae. Results The study population included 33 INHI, 45 V, and 50 NV patients. There were no significant differences in age (P=.98), sex (P=.68), TBSA (P=.18), pulmonary comorbidity (P=.5), or smoking status (P=.92). Outpatient pulmonary sequelae were significantly higher for both INHI and V groups as compared to NV (21% and 17% vs 4%, P=.023, .043). The number of days from discharge to pulmonary sequelae was significantly shorter in the INHI group versus the V group (162±139 days vs 513±314 days, P=.024). Multinomial logistic regression for both INHI and V groups using the variables comorbid pulmonary disease, smoking status, and inpatient course and complications, indicated no effect on post-discharge pulmonary sequelae (all P >.05). All other measures were not significant when comparing INHI to V or NV (all P >.05). Conclusions Both INHI and V groups resulted in higher rates of outpatient pulmonary sequelae independent of inpatient course as compared to NV. While outpatient pulmonary sequelae were not significantly different between INHI and V, the INHI patients presented with complaints earlier. Thus one can conclude that ventilation alone is a significant contributing factor for the long-term pulmonary sequelae reported in this patient population.

scholarly journals NF-κB and FosB mediate inflammation and oxidative stress in the blast lung injury of rats exposed to shock waves

2021 ◽  
Author(s):  
Hong Wang ◽  
Wenjuan Zhang ◽  
Jinren Liu ◽  
Junhong Gao ◽  
Le Fang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Injury ◽  
Shock Waves ◽  
Time Dependent ◽  
Inflammatory Factors ◽  
Control Group ◽  
Dependent Manner ◽  
Total Antioxidant ◽  
Blast Lung Injury ◽  
And Oxidative Stress

Abstract Blast lung injury (BLI) is the major cause of death in explosion-derived shock waves; however, the mechanisms of BLI are not well understood. To identify the time-dependent manner of BLI, a model of lung injury of rats induced by shock waves was established by a fuel air explosive. The model was evaluated by hematoxylin and eosin staining and pathological score. The inflammation and oxidative stress of lung injury were also investigated. The pathological scores of rats’ lung injury at 2 h, 24 h, 3 days, and 7 days post-blast were 9.75±2.96, 13.00±1.85, 8.50±1.51, and 4.00±1.41, respectively, which were significantly increased compared with those in the control group (1.13±0.64; P<0.05). The respiratory frequency and pause were increased significantly, while minute expiratory volume, inspiratory time, and inspiratory peak flow rate were decreased in a time-dependent manner at 2 and 24 h post-blast compared with those in the control group. In addition, the expressions of inflammatory factors such as interleukin (IL)-6, IL-8, FosB, and NF-κB were increased significantly at 2 h and peaked at 24 h, which gradually decreased after 3 days and returned to normal in 2 weeks. The levels of total antioxidant capacity, total superoxide dismutase, and glutathione peroxidase were significantly decreased 24 h after the shock wave blast. Conversely, the malondialdehyde level reached the peak at 24 h. These results indicated that inflammatory and oxidative stress induced by shock waves changed significantly in a time-dependent manner, which may be the important factors and novel therapeutic targets for the treatment of BLI.

scholarly journals First line treatment selection modifies disease course and long-term clinical outcomes in Mycobacterium avium complex pulmonary disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kiyoharu Fukushima ◽  
Seigo Kitada ◽  
Sho Komukai ◽  
Tomoki Kuge ◽  
Takanori Matsuki ◽  
...  
Keyword(s):  
Pulmonary Disease ◽  
Mycobacterium Avium ◽  
Propensity Scores ◽  
Cox Regression ◽  
Line Treatment ◽  
First Line ◽  
Standard Regimen ◽  
Cox Regression Analysis ◽  
First Line Treatment

AbstractThe combination of rifamycin (RFP), ethambutol (EB), and macrolides is currently the standard regimen for treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). However, poor adherence to the standardized regimens recommended by current guidelines have been reported. We undertook a single-centred retrospective cohort study to evaluate the long-term outcomes in 295 patients with MAC-PD following first line treatment with standard (RFP, EB, clarithromycin [CAM]) or alternative (EB and CAM with or without fluoroquinolones (FQs) or RFP, CAM, and FQs) regimens. In this cohort, 80.7% were treated with standard regimens and 19.3% were treated with alternative regimens. After heterogeneity was statistically corrected using propensity scores, outcomes were superior in patients treated with standard regimens. Furthermore, alternative regimens were significantly and independently associated with sputum non-conversion, treatment failure and emergence of CAM resistance. Multivariate cox regression analysis revealed that older age, male, old tuberculosis, diabetes mellitus, higher C-reactive protein, and cavity were positively associated with mortality, while higher body mass index and M. avium infection were negatively associated with mortality. These data suggest that, although different combination regimens are not associated with mortality, first line administration of a standard RFP + EB + macrolide regimen offers the best chance of preventing disease progression in MAC-PD patients.

Long‐term ABA promotes GLK1 degradation through COP1 in a light intensity‐dependent manner to suppress chloroplast development

2021 ◽  
Author(s):  
Juhun Lee ◽  
Bongsoo Choi ◽  
Areum Yun ◽  
Namil Son ◽  
Gyeongik Ahn ◽  
...  
Keyword(s):  
Light Intensity ◽  
Chloroplast Development ◽  
Dependent Manner

scholarly journals Soluble Spike DNA Vaccine Provides Long-Term Protective Immunity against SARS-CoV-2 in Mice and Nonhuman Primates

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 307
Author(s):  
Yong Bok Seo ◽  
You Suk Suh ◽  
Ji In Ryu ◽  
Hwanhee Jang ◽  
Hanseul Oh ◽  
...  
Keyword(s):  
T Cell ◽  
Nonhuman Primates ◽  
Vaccine Candidate ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Dependent Manner ◽  
Viral Loads ◽  
Cell Responses ◽  
Rapid Spread

The unprecedented and rapid spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) has motivated the need for a rapidly producible and scalable vaccine. Here, we developed a synthetic soluble SARS-CoV-2 spike (S) DNA-based vaccine candidate, GX-19. In mice, immunization with GX-19 elicited not only S-specific systemic and pulmonary antibody responses but also Th1-biased T cell responses in a dose-dependent manner. GX-19-vaccinated nonhuman primates seroconverted rapidly and exhibited a detectable neutralizing antibody response as well as multifunctional CD4+ and CD8+ T cell responses. Notably, when the immunized nonhuman primates were challenged at 10 weeks after the last vaccination with GX-19, they had reduced viral loads in contrast to non-vaccinated primates as a control. These findings indicate that GX-19 vaccination provides a durable protective immune response and also support further development of GX-19 as a vaccine candidate for SARS-CoV-2.

scholarly journals Temozolomide Induces the Acquisition of Invasive Phenotype by O6-Methylguanine-DNA Methyltransferase (MGMT)+ Glioblastoma Cells in a Snail-1/Cx43-Dependent Manner

2021 ◽  
Vol 22 (8) ◽  
pp. 4150
Author(s):  
Paweł Kochanowski ◽  
Jessica Catapano ◽  
Maciej Pudełek ◽  
Tomasz Wróbel ◽  
Zbigniew Madeja ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
Treatment Result ◽  
Dependent Manner ◽  
Down Regulation ◽  
Cx43 Expression ◽  
Cell Lineages ◽  
Methylguanine Dna Methyltransferase ◽  
U87 Cells ◽  
Invasive Cell

Glioblastoma multiforme (GBM) recurrences after temozolomide (TMZ) treatment result from the expansion of drug-resistant and potentially invasive GBM cells. This process is facilitated by O6-Methylguanine-DNA Methyltransferase (MGMT), which counteracts alkylating TMZ activity. We traced the expansion of invasive cell lineages under persistent chemotherapeutic stress in MGMTlow (U87) and MGMThigh (T98G) GBM populations to look into the mechanisms of TMZ-induced microevolution of GBM invasiveness. TMZ treatment induced short-term, pro-invasive phenotypic shifts of U87 cells, in the absence of Snail-1 activation. They were illustrated by a transient induction of their motility and followed by the hypertrophy and the signs of senescence in scarce U87 sub-populations that survived long-term TMZ stress. In turn, MGMThigh T98G cells reacted to the long-term TMZ treatment with the permanent induction of invasiveness. Ectopic Snail-1 down-regulation attenuated this effect, whereas its up-regulation augmented T98G invasiveness. MGMTlow and MGMThigh cells both reacted to the long-term TMZ stress with the induction of Cx43 expression. However, only in MGMThigh T98G populations, Cx43 was directly involved in the induction of invasiveness, as manifested by the induction of T98G invasiveness after ectopic Cx43 up-regulation and by the opposite effect after Cx43 down-regulation. Collectively, Snail-1/Cx43-dependent signaling participates in the long-term TMZ-induced microevolution of the invasive GBM front. High MGMT activity remains a prerequisite for this process, even though MGMT-related GBM chemoresistance is not necessary for its initiation.

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