Pulmonary fibrosis, which influences lung function and exacerbates a patient's condition, is the ultimate stage of many lung diseases. Vitamin D deficiency is associated with pulmonary fibrosis and ...impaired lung function, but the underlying mechanism has not yet been fully elucidated. Moreover, vitamin D deficiency may cause over-activation of the renin-angiotensin system (RAS), which aggravates extracellular matrix (ECM) deposition and lung fibrosis. This study aims to investigate the effect of chronic vitamin D deficiency on lung fibrosis in otherwise healthy mice and to explore the role of RAS in this process. Mice were depleted of vitamin D through diet control and were compared with healthy subjects. Chronic vitamin D deficiency destructs lung structures, impairs lung development and stimulates ECM deposition. RAS components are also found to increase. These effects seem to worsen with prolonged vitamin D deficiency. By giving RAS blockers, these changes can be largely rescued. However, a smooth muscle relaxant whose regulatory effect on blood pressure is independent of RAS does not show similar effects. This study demonstrated that chronic vitamin D deficiency may induce RAS activation, which subsequently stimulates the expression of profibrotic factors and activates the fibrotic cascade. This profibrotic effect of RAS is independent of elevated blood pressure.
In all domains of life, elongating RNA polymerases require the assistance of accessory factors to maintain their processivity and regulate their rate. Among these elongation factors, the Spt5/NusG ...factors stand out. Members of this protein family appear to be the only transcription accessory proteins that are universally conserved across all domains of life. In archaea and eukaryotes, Spt5 associates with a second protein, Spt4. In addition to regulating elongation, the eukaryotic Spt4–Spt5 complex appears to couple chromatin modification states and RNA processing to transcription elongation. This review discusses the experimental bases for our current understanding of Spt4–Spt5 function and recent studies that are beginning to elucidate the structure of Spt4–Spt5/RNA polymerase complexes and mechanism of Spt4–Spt5 action. This article is part of a Special Issue entitled: RNA polymerase II Transcript Elongation.
► Spt4–Spt5 is a positive and negative regulator of transcription elongation. ► Spt5/NusG proteins are found in all organisms and are essential for life. ► Spt4–Spt5 links transcription elongation to chromatin remodeling and RNA processing. ► Structural studies are beginning to provide insights into Spt4–Spt5 function.
The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and ...bronchopulmonary dysplasia (BPD) has not been clarified. In this study, we evaluated if these effects ultimately led to functional damage in hyperoxia-induced alveolar cells.
We treated RLE-6TN cells at 85% hyperoxia for 0, 24 and 48 h with Thiamet G (TG), an OGA inhibitor; OSMI-1 (OS), an OGT inhibitor; or with UDP-GlcNAc, which is involved in synthesis of O-GlcNAc as a donor. The metabolic rerouting, cell viability and apoptosis resulting from the changes in O-GlcNAc glycosyltransferase levels were evaluated in RLE-6TN cells after hyperoxia exposure. We constructed rat Park2 overexpression and knockdown plasmmids for in vitro verification and Co-immunoprecipitation corroborated the binding of Parkin and O-GlcNAc. Finally, we assessed morphological detection in neonatal BPD rats with TG and OS treatment.
We found a decrease in O-GlcNAc content and levels of its metabolic enzymes in RLE-6TN cells under hyperoxia. However, the inhibition of OGT function with OSMI-1 ameliorated hyperoxia-induced lung epithelial cell injury, enhanced cell metabolism and viability, reduced apoptosis, and accelerated the cell proliferation. Mitochondrial homeostasis was affected by O-GlcNAc and regulated Parkin.
The results revealed that the decreased O-GlcNAc levels and increased O-GlcNAcylation of Parkin might cause hyperoxia-induced alveolar type II cells injurys.
To understand the effects of thermal shock on microcrack propagation and permeability in coal, thermal shock tests were conducted on coal specimens by using a constant temperature drying oven (105 ...°C) and a SLX program controlled cryogenic tank. The growth and propagation of microcracks were measured with computer tomography (CT) scanning and scanning electron microscope (SEM) tests. Results showed that thermal shocks improved the permeability of coal significantly. Notably, the permeability of coal after thermal shocks increased from 211.31% to 368.99% and was positively correlated with temperature difference. CT scanning images revealed that thermal shocks increased the crack number, crack volume and crack width as well as smoothened and widened the gas flow paths, thereby enhancing coal permeability. Moreover, SEM images showed that heating-cooling shocks created more new microcracks, forming more complex crack propagation paths and better connectivity among microcracks in coal compared to cooling shocks. We proposed a crack propagation criterion for coal to explain the mechanism of crack failure and propagation during thermal shocks. Our experiment results and theoretical analysis indicate that the heating-cooling shock is more effective in damaging and breaking coal than the cooling shock. Thus, it can be used as an alternative approach to enhance coal permeability in the production of coalbed methane (CBM).
Purpose The efficacy of neoadjuvant chemoradiotherapy (NCRT) plus surgery for locally advanced esophageal squamous cell carcinoma (ESCC) remains controversial. In this trial, we compared the survival ...and safety of NCRT plus surgery with surgery alone in patients with locally advanced ESCC. Patients and Methods From June 2007 to December 2014, 451 patients with potentially resectable thoracic ESCC, clinically staged as T1-4N1M0/T4N0M0, were randomly allocated to NCRT plus surgery (group CRT; n = 224) and surgery alone (group S; n = 227). In group CRT, patients received vinorelbine 25 mg/m
intravenously (IV) on days 1 and 8 and cisplatin 75 mg/m
IV day 1, or 25 mg/m
IV on days 1 to 4 every 3 weeks for two cycles, with a total concurrent radiation dose of 40.0 Gy administered in 20 fractions of 2.0 Gy on 5 days per week. In both groups, patients underwent McKeown or Ivor Lewis esophagectomy. The primary end point was overall survival. Results The pathologic complete response rate was 43.2% in group CRT. Compared with group S, group CRT had a higher R0 resection rate (98.4% v 91.2%; P = .002), a better median overall survival (100.1 months v 66.5 months; hazard ratio, 0.71; 95% CI, 0.53 to 0.96; P = .025), and a prolonged disease-free survival (100.1 months v 41.7 months; hazard ratio, 0.58; 95% CI, 0.43 to 0.78; P < .001). Leukopenia (48.9%) and neutropenia (45.7%) were the most common grade 3 or 4 adverse events during chemoradiotherapy. Incidences of postoperative complications were similar between groups, with the exception of arrhythmia (group CRT: 13% v group S: 4.0%; P = .001). Peritreatment mortality was 2.2% in group CRT versus 0.4% in group S ( P = .212). Conclusion This trial shows that NCRT plus surgery improves survival over surgery alone among patients with locally advanced ESCC, with acceptable and manageable adverse events.
The role of cellular senescence in age-related diseases has been fully recognized. In various age-related-chronic lung diseases, the function of alveolar epithelial cells (AECs) is impaired and ...alveolar regeneration disorders, especially in bronchopulmonary dysplasia，pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD), cancer, etc. Except for age-related-chronic lung diseases, an increasing number of studies are exploring the role of cellular senescence in developmental chronic lung diseases, which typically originate in childhood and even in the neonatal period. This review provides an overview of cellular senescence and lung diseases from newborns to the elderly, attempting to draw attention to the relationship between cellular senescence and developmental lung diseases.
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•Cellular senescence occurs from embryonic development to tissue aging.•Senescent cells exhibit four interdependent hallmarks: permanent cell cycle arrest, macromolecular damage, SASP, and deregulated metabolism.•The senescence of type II cells in the lung is a prophase of most pathologies.•Senolytics and Senomorphics are currently important applications in senescence-associated lung diseases.
Alzheimer’s disease (AD) is a progressive neurodegenerative disease that disrupts cognitive function and severely affects the quality of life. Existing drugs only improve cognitive function and ...provide temporary relief of symptoms but do not stop or delay disease progression. Recently, natural medicines, especially Chinese herbal medicines, have gained attention in the treatment of AD due to their antioxidant, anti-inflammatory, and neuroprotective effects. However, conventional oral dosage forms lack brain specificity and have side effects that lead to poor patient compliance. Utilizing nanomedicine is a promising approach to improve brain specificity, bioavailability, and patient compliance. This review evaluates recent advances in the treatment of AD with nanoparticles containing various natural medicines. This review highlights that nanoparticles containing natural medicines are a promising strategy for the treatment of AD. It is believed that this technology can be translated into the clinic, thereby providing opportunities for AD patients to participate in social activities.
Based on the relationship between rockburst and microseismic event indicators, this study proposes that the risk of rockburst in mine working faces, roadways, and even the entire mine should be ...studied through the “double high” risk evaluation of microseismic events. The 43 evaluation indexes of rockburst were optimized into eight indexes by using the expert scoring method. Considering the eight indexes as the basic events and the “double high” risk of microseismic events as the top event, the “double high” accident tree of microseismic events was established. According to the qualitative analysis results of the accident tree, the microseismic activity evaluation index was determined, and the “double high” risk evaluation index system was constructed for microseismic events. The system included three first-level indicators and eight second-level indicators. The fuzzy hierarchical comprehensive evaluation model was used to evaluate the “double high” risk of microseismic events in the Yanbei Coal Mine. In this paper, a microseismic monitoring and evaluation index model is constructed to simplify the existing evaluation system, which is convenient to effectively establish the connection between microseismic monitoring data and rockburst index and provide important theoretical support for underground monitoring and rockburst prevention.
Bronchopulmonary dysplasia (BPD) is a common devastating pulmonary complication in preterm infants. Supplemental oxygen is a lifesaving therapeutic measure used for premature infants with pulmonary ...insufficiency. However, oxygen toxicity is a significant trigger for BPD. Oxidative stress disrupts lung development, accompanied by increased pro-inflammatory cytokines and chemokines expression and immune cells infiltration in lung tissue. Licorice, a typical traditional herbal medicine, is commonly used in the medicine and food industries. 18β-Glycyrrhetinic acid (18β-GA), a primary active ingredient of licorice, has powerful anti-oxidative and anti-inflammatory effects. This study aimed to determine whether 18β-GA has a protective effect on neonatal rats with hyperoxia exposure. Newborn Sprague–Dawley rats were kept in either 21% (normoxia) or 80% O
2
(hyperoxia) continuously from postnatal day (PN) 1 to 14. 18β-GA was injected intragastrically at 50 or 100 mg/kg body weight once a day from PN 1 to 14. We examined the body weight and alveolar development and measured ROS level and the markers of pulmonary inflammation. Mature-IL-1β and NF-κB pathway proteins, and the NLRP3 inflammasome, were assessed; concurrently, caspase-1 activity was measured. Our results indicated that hyperoxia resulted in alveolar simplification and decreased bodyweight of neonatal rats. Hyperoxia increased ROS level and pulmonary inflammation and activated NF-κB and the NLRP3 inflammasome. 18β-GA treatment inhibited the activation of NF-κB and the NLRP3 inflammasome, decreased ROS level and pulmonary inflammation, improved alveolar development, and increased the bodyweight of neonatal rats with hyperoxia exposure. Our study demonstrates that 18β-GA has a protective effect on neonatal rats with hyperoxia exposure.
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