Esculetin, a natural dihydroxy coumarin derived from the Chinese herbal medicine Cortex Fraxini, has demonstrated significant pharmacological activities, including anticancer properties. Ferroptosis, an iron-dependent form of regulated cell death, has garnered considerable attention due to its lethal effect on tumor cells. However, the exact role of ferroptosis in esculetin-mediated anti-hepatocellular carcinoma (HCC) effects remains poorly understood. This study investigated the impact of esculetin on HCC cells both in vitro and in vivo. The findings indicate that esculetin effectively inhibited the growth of HCC cells. Importantly, esculetin promoted the accumulation of intracellular Fe²⁺, leading to an increase in ROS production through the Fenton reaction. This event subsequently induced lipid peroxidation (LPO) and triggered ferroptosis within the HCC cells. The occurrence of ferroptosis was confirmed by the elevation of malondialdehyde (MDA) levels, the depletion of glutathione peroxidase (GSH-Px) activity, and the disruption of mitochondrial morphology. Notably, the inhibitor of ferroptosis, ferrostatin-1 (Fer-1), attenuated the anti-tumor effect of esculetin in HCC cells. Furthermore, the findings revealed that esculetin inhibited the Nrf2-xCT/GPx4 axis signaling in HCC cells. Overexpression of Nrf2 upregulated the expression of downstream SLC7A11 and GPX4, consequently alleviating esculetin-induced ferroptosis. In conclusion, this study suggests that esculetin exerts an anti-HCC effect by inhibiting the activity of the Nrf2-xCT/GPx4 axis, thereby triggering ferroptosis in HCC cells. These findings may contribute to the potential clinical use of esculetin as a candidate for HCC treatment.
Umbelliferones/administration & dosage* ; Ferroptosis/drug effects* ; Carcinoma, Hepatocellular/physiopathology* ; NF-E2-Related Factor 2/genetics* ; Humans ; Liver Neoplasms/physiopathology* ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Animals ; Cell Line, Tumor ; Mice ; Amino Acid Transport System y+/genetics* ; Mice, Inbred BALB C ; Male ; Signal Transduction/drug effects* ; Lipid Peroxidation/drug effects* ; Reactive Oxygen Species/metabolism* ; Mice, Nude

Objective To investigate the effect of Ba Bao Dan(BBD)on cardiac injury induced by doxorubicin in zebrafish.Methods We induced a zebrafish myocardial injury model using the chemotherapeutic drug,doxorubicin.We then examined the effects of different concentrations of BBD on pericardial edema and heart rate under an in vivo microscope.We also examined the inhibitory effects of BBD on neutrophil infiltration in the heart in Tg(mpx:EGFP)transgenic zebrafish.The impacts of BBD on superoxide dismutase,catalase,and malondialdehyde were observed.mRNA expression levels of ferroptosis-related factors,including glutathione peroxidase 4a(gpx4a),prostaglandin-endoperoxide synthase 2(ptgs2),arachidonate 5-lipoxygenase(alox5a),and acyl-CoA synthetase long-chain family member 4(acsl4)were determined by Real-time quantitative polymerase chain reaction.The accumulation of ferrous ions in zebrafish heart was assessed using a fluorescent probe for ferrous ions.Results BBD alleviated doxorubicin-induced pericardial edema and bradycardia in zebrafish,reduced neutrophil infiltration in the heart(P＜0.05),decreased malondialdehyde concentration(P＜0.05),and enhanced the activities of superoxide dismutase and catalase(P＜0.05).BBD also significantly inhibited ferroptosis,reduced the accumulation of ferrous ions in the zebrafish heart,suppressed the expression of ptgs2,alox5a,and acsl4(P＜0.05),and promoted the expression of gpx4a(P＜0.05).Conclusions BBD can attenuate doxorubicin-induced zebrafish myocardial injury and improve cardiac function by inhibiting lipid peroxidation and regulating ferroptosis.

Objective To evaluate the impact of chest blast injury on left ventricular function and myocardial strain with speckle tracking imaging (STI).Methods Fifty healthy New Zealand rabbits were randomly divided into 4 groups.Five rabbits without blast injury were used as a normal group,and the other rabbits were placed in specific semi-enclosed blasting environment in accordance with the different distance of the explosion.With instantaneous detonators,slight,medium and heavy chest blast injury animal models were produced and labeled as A,B,and C group (each n=15),respectively.The left ventricular function was measured with conventional echocardiography and STI.The longitudinal strain (LS) of the left ventricle was measured with two-dimensional strain analysis software and statistically analyzed.Results There was no significant difference of ejection fraction (EF) and fractional shortening (FS) in the left ventricle after chest blast injury between group A and normal group (all P＞0.05),while LS of anterior wall,anterior septum wall and lateral wall of group A significantly decreased compared with those of normal group (all P＜0.05).In group B and C,the left ventricular EF,FS and LS of each segment were lower than those of normal group (all P＜0.05).In group C,the left ventricular EF,FS and LS of each segment were lower than those in group A (all P＜0.05).There was no significant difference of EF and FS between group B and group C.In group C,LS of anterior wall and lateral wall of basal segment and middle segment were lower than those of group B (all P＜0.05).Conclusion STI can reflect functional changes of left ventricle in each segment earlier and more sensitively after chest blast injury.

OBJECTIVETo investigate the relationship between angiotensin converting enzyme (ACE) gene and exercise-induced silent myocardial ischemia (SI) in patients with type 2 diabetes mellitus.

METHODSOne hundred and eight patients suffering from type 2 diabetes mellitus with normal rest electrocardiograph and 50 healthy individuals were selected randomly. SI was diagnosed with treadmill exercise test and ACE genotypes were detected with PCR.

RESULTS(1) The control group and type 2 diabetes mellitus group had similar distribution of ACE genotypes and alleles (P>0.05). Compared with the non-SI group, the SI group had significantly higher ACE D allele prevalence (Chi-square=4.501, P<0.05); however, the two groups had similar prevalence of ACE genotypes (P>0.05). (2) There were no significant differences in clinical characteristics and serum lipoproteins among the three ACE genotypes (II, DD,ID) of type 2 diabetes mellitus (P>0.05). (3) The prevalence of SI in DD group was found to be 68.2%, which was significantly higher than that in II genotype group (39.5%, Chi-square=4.593, P<0.05).

CONCLUSIONACE D allele increases the risk of SI in type 2 diabetes mellitus.

Adult ; Aged ; Diabetes Mellitus, Type 2 ; blood ; genetics ; Exercise ; physiology ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Lipoproteins ; blood ; Male ; Middle Aged ; Myocardial Ischemia ; diagnosis ; genetics ; physiopathology ; Peptidyl-Dipeptidase A ; genetics ; Polymerase Chain Reaction

Objective To explore the clinical features and urgent treatment strategies of open stabbing and penetrating wound of the heart. Methods In recent five years, 22 cases of cardiac trauma patients were sent to our emergency department, among them 19 sustained penetrating wounds produced by sharp instruments, 3 with perforating wounds, produced by firearm in 2 and sharp instrument in one. Emergent thoracotomy was performed in all the patients. The injury involved right auricle in 4, left auricle in 1, right ventricle in 11, left ventricle in 3, and perforating wounds of both right and left ventricles in 3 patients. Results Among them 19 survived, and their cardiac and pulmonary recovered 2 weeks after the operation. Three patients with injury of the great vessel died, one of them died 8 hour after the operation. Conclusion When the patients who presented open wounds on the anterior or posterior chests, showing a low or undetectable blood pressure, which could not raised even with fluid resuscitation with two venous lines or in some of them displaying signs of Beck's triad, open cardiac injury should be seriously suspected, and emergent thoracotomy should be taken in order to rescue the patients.