Artesunate induces ferroptosis by inhibiting the nuclear localization of SREBP2 in myeloma cells.

Objective: Multiple myeloma (MM) is an incurable haematological cancer characterized by abnormal proliferation of plasma cells. The promising therapeutic effect of selective inhibitors of nuclear export in MM reveals the broad therapeutic prospects of nuclear localization intervention. Sterol regulatory element binding protein 2 (SREBP2) is a lipid regulatory molecule that has been implicated in the effect of drug therapy for MM. SREBP2 has been reported to be regulated by the antimalarial drug artesunate (ART) through alteration of its nuclear localization and has been shown to inhibit ferroptosis in other tumours. However, the mechanism through which this might occur has not been clarified in MM. Our study aimed to explore whether ART can induce ferroptosis in MM through nuclear localization of SREBP2. Methods: To evaluate whether ferroptosis is induced by treatment with ART in myeloma, we used two types of myeloma cell lines. We first used a series of molecular approaches and other techniques to investigate the impact of ART on cell growth, production of reactive oxygen species (ROS), Fe2+ levels, lipid peroxidation and expression of genes related to ferroptosis. Then, we further explored the mechanism through which ferroptosis may occur in these cells and the relationship between ferroptosis and the nuclear localization of SREBP2. Results: Upregulation of ROS, Fe2+, and lipid peroxidation as well as inhibition of cell growth were observed in myeloma cells after treatment with ART. Expression of acyl CoA synthase long chain family member 4 (ACSL4) was increased, while glutathione peroxidase 4 (GPX4) expression was reduced in cells treated with ART. ART-induced cell death could be reversed by ferropstatin-1 (Fer-1) and deferoxamine mesylate (DFO). Nuclear localization of SREBP2 in myeloma cells was inhibited, accompanied by downregulation of isopentenyl pyrophosphate (IPP) and GPX4, after treatment with ART. Conclusion: In conclusion, our study demonstrated that the antimalarial drug ART can inhibit nuclear localization of SREBP2, downregulate IPP and GPX4, and eventually trigger ferroptosis in myeloma cells. Through this study, we hope to establish a correlation between nuclear localization pathways and mediation of ferroptosis in myeloma cells and provide an innovative direction for exploration-related therapy.

Activated partial thromboplastin time as a potential biomarker for the diagnosis of tuberculous pleural effusion.

BACKGROUND: The aim of this study was to explore the difference in activated partial thromboplastin time (APTT) levels in patients with tuberculous and non-tuberculous pleural effusion (TPE and non-TPE) and its possible mechanism to provide a new direction for the diagnosis of pleural effusion (PE). METHODS: A total of 61 patients diagnosed with tuberculous pleurisy with pleural effusion at Shunde Hospital of Southern Medical University from July 2013 to September 2020 were selected as the observation group (tuberculosis group). Another 89 patients (45 with malignant pleural effusion (MPE) and 44 with parapneumonic pleural effusion (PPE) composed the control group. The adenosine deaminase (ADA) level in pleural fluid and plasma APTT level were measured in the two groups. RESULTS: The levels of APTT and ADA in the TPE group were significantly higher than the control group, and were 40.03 (37.00, 42.60) (s) and 55.00 (47.00, 69.25) (U/L) for TPE, 29.50 (25.45, 34.20) (s) and 11.90 (9.15, 19.05) (U/L) for malignant pleural effusion (MPE) and 31.35 (27.43, 35.76) (s) and 15.15 (7.40, 35.00) (U/L) for parapneumonic pleural effusion (PPE), respectively. CONCLUSIONS: The level of plasma APTT has certain significance in differentiating tuberculous pleural effusion from nontuberculous pleural effusion.

Serum Creatinine as a Potential Biomarker for the Diagnosis of Tuberculous Pleural Effusion.

BACKGROUND: Previous studies have revealed the disadvantages of traditional methods for the diagnosis of tuberculous pleural effusions (TPEs) and have created interest in exploring other effective biomarkers. Many studies have focused on the correlation between pulmonary diseases and serum creatinine (Cr), a representative biomarker of renal function, but little is known about the direct relationship between Cr and TPE. Our study aimed to explore whether Cr can act as a biomarker for the diagnosis of TPE and to evaluate the correlation between Cr and TPE. MATERIALS AND METHODS: Patients with pleural effusions (PEs) were enrolled in this study. By comparing the concentrations of Cr and adenosine deaminase (ADA) in patients with TPEs and non-TPEs, we determined the sensitivity, specificity, Youden index, and area under the curve for these biomarkers. We generated receiver operating characteristic curves and quantifications to evaluate the diagnostic accuracy. RESULTS: In total, 86 patients (44 with TPE, 25 with malignant pleural effusion (MPE) and 17 with non-tuberculosis infectious PE (NTIPE)) were enrolled in the study. The concentrations of Cr in TPE were significantly higher than those in non-TPE. However, a similar trend was not observed for NTIPE and MPE. The levels of ADA in TPE were significantly higher than those in NTIPE and MPE. CONCLUSION: Cr has the potential for the diagnosis of TPE to some extent though its accuracy is not as good as that of ADA. Further studies are necessary for Cr to be applied in clinical practice for the diagnosis of TPE.