Metabolomic insights into pulmonary fibrosis: a mendelian randomization study.

BACKGROUND: This study leverages a two-sample Mendelian Randomization (MR) approach to explore the causal relationships between 1,400 metabolites and pulmonary fibrosis, using genetic variation as instrumental variables. By adhering to stringent criteria for instrumental variable selection, the research aims to uncover metabolic pathways that may influence the risk and progression of pulmonary fibrosis, providing insights into potential therapeutic targets. METHODS: Utilizing data from the OpenGWAS project, which includes a significant European cohort, and metabolite GWAS data from the Canadian Longitudinal Aging Study (CLSA), the study employs advanced statistical methods. These include inverse variance weighting (IVW), weighted median estimations, and comprehensive sensitivity analyses conducted using the R software environment to ensure the robustness of the causal inferences. RESULTS: The study identified 62 metabolites with significant causal relationships with pulmonary fibrosis, highlighting both risk-enhancing and protective metabolic factors. This extensive list of metabolites presents a broad spectrum of potential therapeutic targets and biomarkers for early detection, underscoring the metabolic complexity underlying pulmonary fibrosis. CONCLUSIONS: The findings from this MR study significantly advance our understanding of the metabolic underpinnings of pulmonary fibrosis, suggesting that alterations in specific metabolites could influence the risk and progression of the disease. These insights pave the way for the development of novel diagnostic and therapeutic strategies, emphasizing the potential of metabolic modulation in managing pulmonary fibrosis.

Induction of Apoptosis by Metabolites of Rhei Radix et Rhizoma (Da Huang): A Review of the Potential Mechanism in Hepatocellular Carcinoma.

Liver cancer is a global disease with a high mortality rate and limited treatment options. Alternations in apoptosis of tumor cells and immune cells have become an important method for detailing the underlying mechanisms of hepatocellular carcinoma (HCC). Bcl-2 family, Caspase family, Fas and other apoptosis-related proteins have also become antagonistic targets of HCC. Da Huang (Rhei Radix et Rhizoma, RR), a traditional Chinese herb, has recently demonstrated antitumor behaviors. Multiple active metabolites of RR, including emodin, rhein, physcion, aloe-emodin, gallic acid, and resveratrol, can successfully induce apoptosis and inhibit HCC. However, the underlying mechanisms of these metabolites inhibiting the occurrence and development of HCC by inducing apoptosis is complicated owing to the multi-target and multi-pathway characteristics of traditional Chinese herbs. Accordingly, this article reviews the pathways of apoptosis, the relationship between HCC and apoptosis, the role and mechanism of apoptosis induced by mitochondrial endoplasmic reticulum pathway and death receptor pathway in HCC and the mechanism of six RR metabolites inhibiting HCC by inducing apoptosis.

Efficacy and Safety of Dahuang Zhechong Pill in Silicosis: A Randomized Controlled Trial.

BACKGROUND: There is no effective therapy for silicosis, and Dahuang Zhechong pill (DHZCP), an ancient Chinese medicine prescription, may have a therapeutic effect on silicosis. This study aims to verify the efficacy and safety of DHZCP in silicosis. METHODS: This is a randomized controlled clinical trial done at Panzhihua Second People's Hospital (Panzhihua City, Sichuan Province, China). Participants diagnosed with silicosis were recruited and randomized to the conventional treatment group (CG) or DHZCP combined with the conventional treatment group (DG). Forced vital capacity % predicted (FVC%), diffusing capacity of the lung for carbon monoxide % predicted (DLCO%), six-minute walk distance (6MWD), peripheral oxygen (SpO2), King's Brief Interstitial Lung Disease Questionnaire (K-BILD), and safety outcomes were measured at baseline and 9 weeks. RESULTS: Fifty-six participants (28 in each group) completed the study, and 53 of them (26 in DG and 27 in CG) completed pulmonary function. At 9 weeks, compared with no DHZCP, DHZCP treatment was associated with significant improvements in FVC% (mean ± SD, 95%CI) (8.2 ± 3.9, 0.3 to 16.0), DLCO% (8.6 ± 3.5, 1.5 to 15.7), SpO2 (3.8 ± 0.7, 2.3 to 5.2), and K-BILD total score (6.0 ± 2.3, 1.4 to 10.7). And, there were no statistical differences of safety outcomes between the two groups. Eight patients accepting DHZCP developed mild diarrhea during the first week, which subsequently resolved on its own. CONCLUSION: DHZCP could improve the pulmonary function, the quality of life, and the exercise capacity of silicosis patients.