A comprehensive cuproptosis score and associated gene signatures reveal prognostic and immunological features of idiopathic pulmonary fibrosis.

Background: Cuproptosis, the most recently identified and regulated cell death, depends on copper ions in vivo. Copper regulates the pathogenesis of Idiopathic pulmonary fibrosis (IPF), but the mechanism of action underlying cuproptosis in IPF remains unclear. Methods: We identified three cuproptosis patterns based on ten cuproptosis-related genes using unsupervised consensus clustering. We quantified these patterns using a PCA algorithm to construct a cuproptosis score. ssGSEA and the Cibersort algorithm assessed the immune profile of IPF patients. GSEA and GSVA were used to analyze the functional differences in different molecular patterns. Drug susceptibility prediction based on cuproptosis scores and meaningful gene markers was eventually screened in combination with external public data sets,in vitro experiments and our cases. Results: Of the three types of cuproptosis-related clusters identified in the study, patients in the clusterA, geneclusterB, and score-high groups showed improved prognoses. Moreover, each cluster exhibited differential immune characteristics, with the subtype showing a poorer prognosis associated with an immune overreaction. Cuproptosis score can be an independent risk factor for predicting the prognosis of IPF patients. GSEA showed a significant functional correlation between the score and cuproptosis. The genes AKAP9, ANK3, C6orf106, LYRM7, and MBNL1, were identified as prognostic-related signatures in IPF patients. The functional role of immune regulation in IPF was further explored by correlating essential genes with immune factors. Also, the nomogram constructed by cumulative information from gene markers and cuproptosis score showed reliable clinical application. Conclusions: Cuproptosis patterns differ significantly in the prognosis and immune characteristics of IPF patients. The cuproptosis score and five gene signatures can provide a reliable reference in the prognosis and diagnosis of IPF.

Association between B-vitamins intake and frailty among patients with chronic obstructive pulmonary disease.

PURPOSE: Gain insight into the impact of B vitamins, including vitamin B1, vitamin B2, niacin, vitamin B6, total folate, and vitamin B12 on the risk of frailty in patients with chronic obstructive pulmonary disease (COPD). METHODS: This study was an American population-based cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES). A total of 1201 COPD patients were included in the analysis. Of these, the intake of B vitamins was determined by the two 24-h recall interviews. We followed the method constructed by Hakeem et al. to calculate the frailty index (FI), which is used as a reliable tool to assess the debilitating status of patients with COPD. Missing data were imputed by the MissForest method based on random forests. Multivariate logistic regression model and inverse probability weighted based on propensity scores were used to correct for confoundings. RESULTS: Logistic regression models showed that vitamin B6 intake was negatively correlated with frailty risk in COPD patients, while other B vitamins including B1, B2, niacin (vitamin B3), total folic acid and vitamin B12 were not. After adjusting for covariates, the association between vitamin B6 and frailty risk (adjusted OR = 0.80, 95%CI = 0.66-0.95, P = 0.013) remained significant. At the same time, sensitivity analysis proves the robustness of the results. CONCLUSION: COPD patients with lower vitamin B6 intake have a higher risk of frailty. However, intake of vitamin B1, B2, niacin, total folic acid, and vitamin B12 was not associated with frailty risk in COPD patients.

D-Limonene Is a Potential Monoterpene to Inhibit PI3K/Akt/IKK-α/NF-κB p65 Signaling Pathway in Coronavirus Disease 2019 Pulmonary Fibrosis.

At the time of the prevalence of coronavirus disease 2019 (COVID-19), pulmonary fibrosis (PF) related to COVID-19 has become the main sequela. However, the mechanism of PF related to COVID (COVID-PF) is unknown. This study aimed to explore the key targets in the development of COVID-PF and the mechanism of d-limonene in the COVID-PF treatment. The differentially expressed genes of COVID-PF were downloaded from the GeneCards database, and their pathways were analyzed. d-Limonene was molecularly docked with related proteins to screen its pharmacological targets, and a rat lung fibrosis model was established to verify d-limonene's effect on COVID-PF-related targets. The results showed that the imbalance between collagen breakdown and metabolism, inflammatory response, and angiogenesis are the core processes of COVID-PF; and PI3K/AKT signaling pathways are the key targets of the treatment of COVID-PF. The ability of d-limonene to protect against PF induced by bleomycin in rats was reported. The mechanism is related to the binding of PI3K and NF-κB p65, and the inhibition of PI3K/Akt/IKK-α/NF-κB p65 signaling pathway expression and phosphorylation. These results confirmed the relationship between the PI3K-Akt signaling pathway and COVID-PF, showing that d-limonene has a potential therapeutic value for COVID-PF.

Allicin Improves Lung Injury Induced by Sepsis via Regulation of the Toll-Like Receptor 4 (TLR4)/Myeloid Differentiation Primary Response 88 (MYD88)/Nuclear Factor kappa B (NF-κB) Pathway.

BACKGROUND The aim of this study was to assess the effects and mechanisms of allicin in a sepsis-induced lung injury in vivo study. MATERIAL AND METHODS The rats (n=54) were divided into 6 groups: Normal, DMSO, LPS, LPS+LD, LPS+MD, and LPS+HD groups. After being treated by different methods, we collected the lung tissues of different groups and evaluated the pathology by HE staining and positive apoptosis cells by TUNEL. We assessed the W/D ratio, inflammatory cytokines (TNF-alpha, IL-6 and IL-1ß), and relative protein expressions (TLR4, MyD88, NF-kappaB, caspase-3, and caspase-9) by IHC assay. RESULTS Compared with LPS group, the lung injury and positive cell number of allicin treated groups were significantly improved with dose-dependent (P<0.05, respectively) and the W/D ratio and TNF-alpha, IL-6 and IL-1ß concentration were significantly down-regulation compared with those of LPS group with dose-dependent (P<0.05, respectively). By IHC, the TLR4, MyD88, NF-kappaB, caspase-3 and caspase-9 protein activities of allicin treated groups were significantly suppressed compared with those of LPS group (P<0.05, respectively) in lung tissues. CONCLUSIONS This in vivo study shows that allicin improved sepsis-induced lung injury by regulation of TLR4/MyD88/NF-kappaB.