Objective: To elucidate the effects of chlorogenic acid (CGA), a bioactive polyphenol compound prevalent in traditional Chinese medicine and various foods, including Lonicera japonica Thunb. (Jin Yin Hua), Eucommia ulmoides Oliv. (Du Zhong Ye), tea, and coffee, on cardiomyocyte ferroptosis and heart failure. Methods: We assessed the effect of CGA on cardiac function using a mouse model of heart failure induced by transverse aortic constriction (TAC). These indicators included the left ventricular ejection fraction (LVEF), fractional shortening (LVFS), end-systolic volume (LVESV), end-diastolic volume (LVEDV), end-systolic diameter (LVESD), and end-diastolic diameter (LVEDD). An isoprenaline hydrochloride (ISO)-induced H9c2 cardiomyocyte cell model was also established, and the cells were treated with various concentrations of CGA. To assess the effect of CGA on ferroptosis in cardiomyocytes, we measured cell viability and evaluated the levels of intracellular reactive oxygen species (ROS), ferrous ions (Fe2+), and lipid peroxidation using fluorescent staining. To clarify the ferroptosis signaling pathway regulated by CGA, western blotting was used to examine the expression of ferroptosis biomarkers, specifically solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), in H9c2 cardiomyocytes and mouse myocardial tissues. Results: CGA significantly enhanced cardiac performance indices such as LVEF, LVFS, LVESV, LVEDV, LVESD, and LVEDD. H9c2 cardiomyocytes exposed to ISO showed decreased cell viability and increased ROS levels, Fe2+ content, and lipid peroxidation levels. However, CGA treatment significantly ameliorated these changes. Additionally, in both H9c2 cardiomyocytes and myocardial tissue obtained from mice with TAC, CGA increased the expression of ferroptosis-related proteins, including SLC7A11 and GPX4. Conclusion CGA has the potential to enhance cardiac function and diminish lipid peroxidation and ROS levels in cardiomyocytes via the SLC7A11/GPX4 signaling pathway. This process alleviates ferroptosis in cardiomyocytes. These results provide new insights into the clinical use of CGA and the management of heart failure.

Objective To explore the effect of 14-3-3 β gene on biological behavior ofglioma cell line and its mechanism.Methods Conventional cultured SVGp12,U251,U87 and SHG-44 cell lines and U251 cells silenced by 14-3-3[β-small interfering RNA (siRNA) were collected; real time-PCR and Western blotting were used to detect the 14-3-3β gene and protein expressions in these cells.Conventional cultured U251 cells at logarithmic phase were divided into three groups:experimental group (14-3-3β-siRNA transfection),negative control group (siRNA transfection) and blank control group; 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay was used to assess the proliferation of U251 cells,flow cytometry was used to test the cell apoptosis,and cell migration was analyzed by Transwell chamber assay.Results As compared with those in the normal glial cells,14-3-3β gene and protein expression levels in the glioma cells were significantly higher (P＜0.05); as compared with negative control and blank control groups,U251 cells in the experimental group had significantly decreased gene and protein expressions of 14-3-3β,decreased proliferation and migration abilities,significantly increased apoptosis rate and p53 mRNA level (P＜0.05).Conclusion Silence of 14-3-3 β gene decreases U251 cells proliferation and migration through p53 mediated pathway; consequently,a new explanation about how 14-3-3 β regulates glioma cells proliferation and migration can be clarified,and a potential target for glioma treatment can be provided.

ObjectiveTo establish and evaluate a mouse model of heart failure with Qi deficiency syndrome. MethodForty-four KM mice were randomly divided into sham operation group， model group， and modified Si Junzitang group （12.89 g·kg^-1）. The model group and the modified Si Junzitang group underwent thoracic aortic constriction （TAC）， while the sham operation group only underwent suture without constriction. Echocardiography and pathological examination were used to assess the heart failure model and evaluate the pharmacological effects. Macroscopic characterization， microscopic biology， and formula identification were conducted to collect general signs， body weight， open-field behavior， grip strength， mitochondrial ultrastructure， and other macroscopic and microscopic characteristics of mice. Mitochondrial fission and fusion protein expression were measured to determine the syndrome type. ResultEight weeks after TAC， compared with the sham operation group， the model group showed a significant decrease in left ventricular ejection fraction （LVEF） （P<0.01）， and modified Si Junzitang improved LVEF in mice （P<0.05）. Hematoxylin-eosin （HE） staining of the heart showed inflammatory cell infiltration and thickening of blood vessel walls in the model group， which was significantly improved by modified Si Junzitang. After 6-8 weeks， compared with the sham operation group and the modified Si Junzitang group， the model group exhibited significant hair loss， hair yellowing， decreased activity， and depression. Moreover， compared with the sham operation group， the model group had a significantly lower increase in body weight （P<0.05）， while the modified Si Junzitang group showed a significant increase in body weight （P<0.05） compared with the model group. After 6-8 weeks， compared with the sham operation group， the model group showed a significant decrease in open-field distance and speed （P<0.05）， while the modified Si Junzitang group exhibited significantly improved open-field distance and speed in the 8^th week （P<0.05）. After 6-8 weeks， compared with the sham operation group， the model group exhibited a significant decrease in maximum grip strength （P<0.05）， while the modified Si Junzitang group showed a significant increase in maximum grip strength 8 weeks after TAC （P<0.05）. Transmission electron microscopy of the gastrocnemius muscle showed uneven muscle tissue matrix， mitochondrial swelling， increased volume， matrix dissolution， ridge loss， and vacuolization in the model group， while modified Si Junzitang improved mitochondrial swelling， ridge fracture， and matrix vacuolization. Western blot analysis showed that the expression of the kinetic associated protein 1 （DRP1） in the gastrocnemius muscle of the model group significantly increased （P<0.01）， and the expression of mitochondrial fusion hormone 1 （MFN1） significantly decreased （P<0.05） as compared with those in the sham operation group. Furthermore， compared with the model group， the modified Si Junzitang group exhibited a significant decrease in the expression of DRP1 （P<0.05） and a significant increase in MFN1 expression （P<0.01）. ConclusionMice exhibited significant manifestations of qi deficiency syndrome 6-8 weeks after TAC， accompanied by abnormal mitochondrial morphology and function in the gastrocnemius muscle， which were significantly improved by modified Si Junzitang.

Objective: To investigate the role and mechanism of the heat-clearing and detoxifying drug Laggerae Herba in regulating the nuclear factor-erythroid 2-related factor-2(Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway to inhibit ferroptosis and improve chronic heart failure induced by transverse aortic arch constriction in mice. Methods: Twenty-four male ICR mice were divided into the sham (n=6) and transverse aortic arch constriction groups (n=18) according to the random number table method. The transverse aortic arch constriction group underwent transverse aortic constriction surgery to establish models. After modeling, the transverse aortic arch constriction group was further divided into the model, captopril, and Laggerae Herba groups according to the random number table method, with six mice per group. The captopril (15 mg/kg) and Laggerae Herba groups (1.95 g/kg) received the corresponding drugs by gavage, whereas the sham operation and model groups were administered the same volume of ultrapure water by gavage once a day for four consecutive weeks. After treatment, the cardiac function indexes of mice in each group were detected using ultrasound. The heart mass and tibia length were measured to calculate the ratio of heart weight to tibia length. Hematoxylin and eosin staining were used to observe the pathological changes in myocardial tissue. Masson staining was used to observe the degree of myocardial fibrosis. Wheat germ agglutinin staining was used to observe the degree of myocardial cell hypertrophy. Prussian blue staining was used to observe the iron deposition in myocardial tissue. An enzyme-linked immunosorbent assay was used to detect the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and glutathione (GSH) contents in mice serum. Colorimetry was used to detect the malondialdehyde (MDA) content in mice serum. Western blotting was used to detect the Nrf2, GPX4, SLC7A11, and ferritin heavy chain 1 (FTH1) protein expressions in mice cardiac tissue. Results: Compared with the sham group, in the model group, the ejection fraction (EF) and fractional shortening (FS) of mice decreased, the left ventricular end-systolic volume (LVESV) and left ventricular end-systolic diameter (LVESD) increased, the left ventricular anterior wall end-systolic thickness (LVAWs) and left ventricular posterior wall end-systolic thickness (LVPWs) decreased, the ratio of heart weight to tibia length increased, the myocardial tissue morphology changed, myocardial fibrosis increased, the cross-sectional area of myocardial cells increased, iron deposition appeared in myocardial tissue, the serum NT-proBNP and MDA levels increased, the GSH level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue decreased (P<0.05). Compared with the model group, in the captopril and Laggerae Herba groups, the EF, FS, and LVAWs increased, the LVESV and LVESD decreased, the ratio of heart weight to tibia length decreased, the myocardial cells were arranged neatly, the degree of myocardial fibrosis decreased, the cross-sectional area of myocardial cells decreased, the serum NT-proBNP level decreased, and the GSH level increased. Compared with the model group, the LVPWs increased, the iron deposition in myocardial tissue decreased, the serum MDA level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue increased (P<0.05) in the Laggerae Herba group. Conclusion Laggerae Herba improves the cardiac function of mice with chronic heart failure caused by transverse aortic arch constriction, reduces the pathological remodeling of the heart, and reduces fibrosis. Its mechanism may be related to Nrf2/SLC7A11/GPX4 pathway-mediated ferroptosis.