Metabolomics has been used to explore the molecular mechanism and screen biomarkers. However, the critical metabolic signatures associated with benzene-induced hematotoxicity remain elusive. Here, we performed a plasma metabolomics study in 86 benzene-exposed workers and 76 healthy controls, followed by a validation analysis in mice, to investigate the dynamical change of the metabolic profile. We found that 8 fatty acids were significantly altered in both benzene-exposed worker and benzene-exposed animal models. These metabolites were significantly associated with S-phenylmercapturic acid and WBC, and they mediated the benzene-induced WBC decline. Furthermore, in vivo results confirm that fatty acid levels were dynamically altered, characterized by a decrease at 15 days and then sharp increases at 30 and 45 days. Following these identified fatty acids, the potential metabolic pathways were investigated. Fatty acids, as precursors for fatty acid oxidation, may disturb the balance of fatty acid biosynthesis and degradation. Our results reveal that fatty acid metabolism was strongly reprogrammed after benzene exposure. This abnormal change of fatty acids might be the key metabolic signature associated with benzene-induced hematotoxicity.
31 October 2022 in Clinical and Experimental Medicine
As an immunomodulatory agent with antitumor activity, lenalidomide has been evaluated for its value in diffuse large B-cell lymphoma (DLBCL). We performed a meta-analysis to gain a better understanding of the efficacy and safety of lenalidomide in DLBCL. PubMed, Cochrane Library, and Embase were searched up to March 2022 for potential studies. The pooled hazard ratio (HR) and relative risk (RR) with 95% confidence interval (CI) were estimated by the fixed/random effects model. Overall, 6 randomized controlled trials including 1938 patients were included. The complete response rate (CRR) of the group containing lenalidomide was 47.7% (95%CI 28.5–67.2%), which was higher than the 37.8% (95%CI 16.7–61.5%) of the control group without lenalidomide (RR = 1.11, 95%CI 1.03–1.20,P = 0.008). The overall estimation of survival showed a benefit for progression-free survival (PFS) (HR = 0.77, 95%CI 0.66–0.90,P = 0.001) but not overall survival (OS) or event-free survival (EFS). The lenalidomide group had a significant incidence of grade ≥ 3 hematological adverse events (AEs) involving neutropenia (RR = 1.56, 95%CI 1.15–2.11,P = 0.004) and febrile neutropenia (RR = 1.81, 95%CI 1.31–2.49,P < 0.001), with the incidence of neutropenia (48.3%, 95%CI 37.5–59.1%) being highest. In conclusion, addition of lenalidomide results in a higher CRR and better PFS but a higher incidence of grade ≥ 3 hematological AEs involving neutropenia and febrile neutropenia.