MiR-141 attenuates sepsis-induced cardiomyopathy by targeting DAPK1.

OBJECTIVE: To discuss the possible effects of microRNA-141 (miR-141) in sepsis-induced cardiomyopathy (SIC) via targeting death-associated protein kinase 1 (DAPK1). METHODS: An SIC mouse model was constructed by abdominal injection of lipopolysaccharide (LPS) and divided into control, LPS, LPS + pre-miR-141, and LPS + anti-miR-141 groups. Hemodynamic indicators and heart function indexes of mice were detected. ELISA was used to determine the serum levels of inflammatory cytokines, while TUNEL staining to observe the apoptosis of myocardial cells of mice, as well as qRT-PCR and Western blotting to clarify the expression of miR-141 and DAPK1. Lastly, in vitro experiment was also conducted on the primary neonatal rat ventricular cardiomyocytes (NRVCMs) to validate the results. RESULTS: Mice in the LPS group, as compared to the control group, had lower left ventricular ejection fraction, left ventricular fractional shortening, left ventricular systolic pressure, and ±dp/dt, but a higher left ventricular end-diastolic pressure, while the serum expression of IL-1ß, IL-6, TNF-α, and cTn-T was up-regulated evidently with the increased apoptotic index of myocardial tissues. However, miR-141 and Bcl-2/Bax were down-regulated with elevated DAPK1 and cleaved caspase-3. The above changes were ameliorated in mice from the LPS + pre-miR-141 group relative to the LPS group, while those in the LPS + anti-miR-141 group were further deteriorated. In vitro experiment showed that miR-141 overexpression could reduce the apoptosis of LPS-induced NRVCMs and the levels of inflammatory cytokines with the increased cell viability. CONCLUSION: MiR-141 could decrease inflammatory response and reduce myocardial cell apoptosis by targeting DAPK1, thereby playing the promising protective role in SIC.

Temperature-sensitive bone mesenchymal stem cells combined with mild hypothermia reduces neurological deficit in rats of severe traumatic brain injury.

BACKGROUND: To explore the combined influences of temperature-sensitive bone mesenchymal stem cells (tsBMSCs) and mild hypothermia (MH) on neurological function and glucose metabolism in rats with severe traumatic brain injury (TBI). METHODS: SD rats were randomly divided into sham, TBI, TBI + MH, TBI + BMSCs and TBI + MH +tsBMSCs groups. Then, the brain water content, serum-specific proteins (S100ß, NSE, LDH, and CK), and blood glucose at different time points were measured. Furthermore, GLUT-3 expression was detected by Western blotting, and apoptotic rate was determined by TUNEL staining. RESULTS: After TBI rat establishment, the brain injury resulted in significant increases in mNSS scores and brain water content, and upregulations in serum levels of S100ß, NSE, LDH and CK, and blood glucose, with the elevated cell apoptotic rate in the injured cortex. However, these changes were reversed by MH alone, BMSCs alone, or combination treatment of MH and tsBMSCs in varying degrees, and the combination treatment was superior to the treatment with BMSCs or MH alone. CONCLUSION: Combination therapy of tsBMSCs and MH can reduce the neuronal apoptosis in severe TBI rats, with the suppression of serum biomarkers and hyperglycemia, contributing to the recovery of neurological functions. ABBREVIATIONS: tsBMSCs: temperature-sensitive bone mesenchymal stem cells; MH: mild hypothermia; TBI: traumatic brain injury; mNSS: modified Neurological Severity Score.

In vitro evidence of baicalein's inhibition of the metabolism of zidovudine (AZT).

BACKGROUND: Herb-drug interaction (HDI) has been regarded as a key factor limiting the clinical application of herbs and drugs. AIMS: Potential baicalein-zidovudine (AZT) interaction was predicted in the present study. METHODS: In vitro evaluation of baicalein's inhibition towards human liver microsomes (HLMs)-catalyzed metabolism of zidovudine (AZT) was performed. Dixon and Lineweaver-Burk plots were used to determine the inhibition kinetic type, and second plot with the slopes from Lineweaver-Burk plot versus the concentrations of baicalein was employed to calculate the inhibition parameter (Ki). In combination with the in vivo concentration of baicalein, in vitro-in vivo extrapolation (IVIVE) was carried out to predict in vivo baicalein-AZT interaction. RESULTS: Competitive inhibition of baicalein towards AZT metabolism was demonstrated, and the Ki value was calculated to be 101.2 µM. The value of AUCi/AUC was calculated to be 2. CONCLUSION: Potential baicalein-AZT interaction was indicated in the present study, indicating the need for monitoring when AZT is co-administrated with baicalein or baicalein-containing herbs.