Search

Introduction: Spinal cord injury (SCI) is a central nervous system injury that is primarily traumatic and manifests as motor, sensory, and autonomic dysfunction below the level of damage. Our previous studies confirmed the ability of zinc to protect mitochondria, protect neurons and promote spinal cord recovery. However, the role of zinc in Parthanatos is unknown. Aim: We investigated the effects of zinc in Parthanatos from oxidative stress and mitophagy. We elucidated the role of SIRT3 in providing new ideas for treating spinal cord injury. The Results: Zinc protected SCI mice by regulating Parthanatos. On the one hand, zinc eliminated ROS directly through SIRT3 deacetylation targeting SOD2 to alleviate Parthanatos. On the other hand, zinc eliminated ROS indirectly through SIRT3‐mediated promotion of mitophagy to alleviate Parthanatos. Conclusion: Zinc defends against Parthanatos and promotes functional recovery after spinal cord injury through SIRT3‐mediated anti‐oxidative stress and mitophagy. [ABSTRACT FROM AUTHOR]

Introduction: The GAP model was widely used as a simple risk "screening" method for patients with idiopathic pulmonary fibrosis (IPF). Objectives: We sought to validate the GAP model in Chinese patients with IPF to evaluate whether it can accurately predict the risk for mortality. Methods: A total of 212 patients with IPF diagnosed at China‐Japan Friendship Hospital from 2015 to 2019 were enrolled. The latest follow‐up ended in September 2022. Cumulative mortality of each GAP stage was calculated and compared based on Fine‐Gray models for survival, and lung transplantation was treated as a competing risk. The performance of the model was evaluated in terms of both discrimination and calibration. Results: The cumulative mortality in patients with GAP stage III was significantly higher than that in those with GAP stage I or II (Gray's test p < 0.0001). The Harrell c‐index for the GAP calculator was 0.736 (95% CI: 0.667–0.864). The discrimination for the GAP staging system were similar with that for the GAP calculator. The GAP model overestimated the mortality rate at 1‐ and 2‐year in patients classified as GAP stage I (6.90% vs. 1.77% for 1‐year, 14.20% vs. 6.78% for 2‐year). Conclusions: Our findings indicated that the GAP model overestimated the mortality rate in mild group. [ABSTRACT FROM AUTHOR]

The dysfunction of type II alveolar epithelial cells (AECIIs), mainly manifested by apoptosis, has emerged as a major component of idiopathic pulmonary fibrosis (IPF) pathophysiology. A pivotal mechanism leading to AECIIs apoptosis is mitochondrial dysfunction. Recently, interleukin (IL)‐17A has been demonstrated to have a pro‐fibrotic role in IPF, though the mechanism is unclear. In this study, we report enhanced expression of IL‐17 receptor A (IL‐17RA) in AECIIs in lung samples of IPF patients, which may be related to the accumulation of mitochondria in AECIIs of IPF. Next, we investigated this relationship in bleomycin (BLM)‐induced PF murine model. We found that IL‐17A knockout (IL‐17A−/−) mice exhibited decreased apoptosis levels of AECIIs. This was possibly a result of the recovery of mitochondrial morphology from the improved mitochondrial dynamics of AECIIs, which eventually contributed to alleviating lung fibrosis. Analysis of in vitro data indicates that IL‐17A impairs mitochondrial function and mitochondrial dynamics of mouse primary AECIIs, further promoting apoptosis. PTEN‐induced putative kinase 1 (PINK1)/Parkin signal‐mediated mitophagy is an important aspect of mitochondria homeostasis maintenance. Our data demonstrate that IL‐17A inhibits mitophagy and promotes apoptosis of AECIIs by decreasing the expression levels of PINK1. We conclude that IL‐17A exerts its pro‐fibrotic effects by inducing mitochondrial dysfunction in AECIIs by disturbing mitochondrial dynamics and inhibiting PINK1‐mediated mitophagy, thereby leading to apoptosis of AECIIs. [ABSTRACT FROM AUTHOR]

Background: Serum Krebs von den Lungen‐6 (KL‐6) has been reported to be elevated in patients with idiopathic pulmonary fibrosis (IPF). Objective: The aim of this study was to evaluate the diagnostic value of KL‐6 and whether the expression value of KL‐6 could indicate the severity of the disease in IPF patients. To address this question, it is necessary to see whether the patients' physical characteristics and other clinical conditions could affect the baseline KL‐6 level. Design We conducted a study of 100 patients who were diagnosed with IPF. Lung function, computed tomography (CT), and serological lab tests data were analyzed. Results: The tests showed that there is a significant elevation of KL‐6 in IPF patients compared with other interstitial lung disease (ILD) and healthy controls. It was noted that serum KL‐6 is a stable biomarker not affected by lung infection and smoking, though IPF patients with antinuclear antibody (ANA) showed higher KL‐6 levels. KL‐6, in conjunction with poor pulmonary function and higher radiological fibrosis scores, indicates the severity of the disease but not poor survival. Conclusions: It is identified that serum KL‐6 is a useful noninvasive biomarker to help improve the certainty of IPF diagnosis from other interstitial lung disease and assist evaluation of disease severity and prognosis. [ABSTRACT FROM AUTHOR]

New Findings: •What is the central question of this study?The aim was to explore the effects and underlying mechanisms of H2 on bleomycin‐induced pulmonary fibrosis.•What are the main findings and its importance?Our results indicate that, in bleomycin‐induced pulmonary fibrosis, H2 inhalation attenuated oxidative stress and reversed the pulmonary epithelial‐to‐mesenchymal transition process by reducing reactive oxygen species production and inhibiting the expression of transforming growth factor‐β1, α‐smooth muscle actin and collagen I to improve fibrotic injury and exert anti‐fibrogenic effects. Thus, H2 inhalation has promising therapeutic potential as a useful adjuvant treatment for patients with idiopathic pulmonary fibrosis, which deserves further study and evaluation. Hydrogen (H2) can protect against tissue damage. The effect of H2 inhalation therapy on the pathogenesis of pulmonary fibrosis remains unknown. This study was designed to explore the effects and underlying mechanisms of H2 inhalation on bleomycin (BLM)‐induced pulmonary fibrosis. A rat model of pulmonary fibrosis was established with BLM. Rats were randomly divided into control and H2 inhalation groups. Haematoxylin and Eosin staining and Mason's Trichrome staining were performed to evaluate pulmonary fibrosis injury, inflammatory cell infiltration, structural disorder and collagen deposition. qRT‐PCR and western blot assays were used to determine the expression of TNF‐α, TGF‐β1, α‐SMA, E‐cadherin, N‐cadherin, vimentin, VEGF and collagen type I at both mRNA and protein levels. The contents of reactive oxygen species, TGF‐β1, TNF‐α, malondialdehyde and hydroxyproline were determined with biochemical test kits or ELISA kits. Bleomycin‐stimulated rats exhibited typical symptoms of pulmonary fibrosis, which featured an increase in collagen deposition, alveolitis, fibrosis and parenchymal structural disorder in the lung. However, BLM‐induced oxidative stress was attenuated by H2 inhalation therapy, which reduced the contents of reactive oxygen species, malondialdehyde and hydroxyproline, enhanced the activity of glutathione peroxidase and decreased the expression of TGF‐β1 and TNF‐α. In addition, H2 inhalation also inhibited BLM‐induced epithelial‐to‐mesenchymal transition by inhibiting TGF‐β1, increasing the expression level of the epithelial cell marker E‐cadherin, and decreasing the expression level of the mesenchymal cell marker vimentin in a time‐dependent manner. In addition, H2 inhalation downregulated α‐SMA expression and suppressed collagen I generation, exerting anti‐fibrogenic effects. Hydrogen inhalation therapy attenuates BLM‐induced pulmonary fibrosis by inhibiting TGF‐β1, relevant oxidative stress and epithelial‐to‐mesenchymal transition. [ABSTRACT FROM AUTHOR]