LuQi formula attenuates Cardiomyocyte ferroptosis via activating Nrf2/GPX4 signaling axis in heart failure.

BACKGROUND: The terminal stage of all cardiovascular diseases typically culminates in heart failure (HF), with no effective intervention available to halt its progression. LuQi formula (LQF) has been employed in clinical for numerous years to significantly ameliorate cardiac function in HF patients. Nevertheless, the underlying mechanism of LQF's efficacy remains inadequately comprehended. Cardiomyocyte ferroptosis has served as a pathogenic mechanism in HF. The goal of the current experiment was to ascertain whether LQF ameliorates HF by preventing cardiomyocyte ferroptosis and to elucidate the intrinsic mechanism involved. PURPOSE: This research objective is to investigate the impact and underlying mechanism of LQF attenuating cardiomyocyte ferroptosis in heart failure. METHODS: Transverse aortic constriction (TAC) was performed to construct the HF mouse model. Neonatal rat cardiomyocytes (NRCMs) were subjected to in vitro experiments. High-performance liquid chromatography (HPLC) identified the bioactive compounds in LQF. Transcriptomic and quantitative proteomic analyses revealed the potential targets of LQF anti-HF. Specifically, histological staining evaluated cardiac hypertrophy and fibrosis. Transmission electron microscopy (TEM) observed mitochondrial morphology. The content of Fe2+, ROS, MDA, GSH, and GSSH was detected using kits. Molecular docking evaluated the binding activities between essential active ingredients of LQF and critical proteins of cardiomyocyte ferroptosis. Mechanistically, the expression levels of Nrf2, Keap1, HO-1, SLC7A11, and GPX4 were evaluated using qPCR, Western blot (WB), or immunohistochemical staining. RESULTS: The primary nine active ingredients in LQF were detected. Transcriptomic and proteomic analyses demonstrated that LQF may ameliorate HF by preventing cardiomyocyte ferroptosis. Histomorphometric analyses revealed that LQF attenuates myocardial hypertrophy and fibrosis. TEM revealed that LQF diminished mitochondrial shrinkage and increased membrane density in myocardial tissue. Additionally, LQF diminished reactive oxygen species (ROS) generation in cardiomyocytes and suppressed cardiomyocyte ferroptosis. Furthermore, the molecular docking technique revealed that the primary active ingredients of LQF had suitable binding activities with Nrf2, GPX4, and SLC7A11. Western analysis further verified that LQF activated the Nrf2/GPX4 signaling axis. decreased SLC7A11 and HO-1 expression. CONCLUSIONS: These results demonstrated that LQF prevents cardiomyocyte ferroptosis via activating Nrf2/GPX4 signaling axis and suppressing SLC7A11 and HO-1 expression. Concurrently, it contributed to elucidating the intrinsic mechanism of LQF and provided a scientific rationale for its development as a novel cardiovascular therapeutic drug.

[Emergency Management of Medical Equipment in Designated Hospitals for Public Health Emergencies].

Medical supply is a key resource for responding to public health emergencies and maintaining people's lives and health. As the medical equipment management department, the medical devices department is mainly responsible for the procurement, supply, technical support, management and coordination of medical equipment and medical consumables, playing an important role in epidemic prevention and control. Through the analysis of the expansion cases of designated hospitals, the experience of emergency management of medical equipment has been accumulated, which has strong practicability and replicability.

LuQi Formula relieves ventricular remodeling through improvement of HIF-1α-mediated intestinal barrier integrity.

BACKGROUND: Ventricular remodeling is the adaptive process in which the heart undergoes changes due to stress, leading to heart failure (HF). The progressive decline in cardiac function is considered to contribute to intestinal barrier impairment. LuQi Formula (LQF) is a traditional Chinese medicine preparation widely used in the treatment of ventricular remodeling and HF. However, the role of LQF in the impairment of intestinal barrier function induced by ventricular remodeling remains unclear. MATERIALS AND METHODS: Ventricular remodeling was induced in rats by permanently ligating the left anterior descending branch coronary artery, and cardiac function indexes were assessed using echocardiography. Heart and colon tissue morphology were observed by hematoxylin-eosin, Masson's trichrome and Alcian Blue Periodic acid Schiff staining. Myocardial cell apoptosis was detected using TUNEL and immunohistochemistry. Circulatory levels of brain natriuretic peptide (BNP), intestinal permeability markers endotoxin, D-lactate and zonulin, as well as inflammatory cytokines tumor necrosis factor alpha and interleukin-1 beta were measured by Enzyme-linked immunosorbent assay. Expression levels of tight junction (TJ) proteins and hypoxia-inducible factor-1 alpha (HIF-1α) in colon tissue were detected by immunofluorescence, immunohistochemistry and western blotting. Cardiac function indexes and intestinal permeability markers of patients with HF were analyzed before and after 2-4 months of LQF treatment. RESULTS: LQF protected cardiac function and alleviated myocardial fibrosis and apoptosis in rats with ventricular remodeling. LQF protected the intestinal barrier integrity in ventricular remodeling rats, including maintaining colonic tissue morphology, preserving the number of goblet cells and normal expression of TJ proteins. Furthermore, LQF upregulated the expression of HIF-1α protein in colon tissue. Intervention with a HIF-1α inhibitor weakened the protective effect of LQF on intestinal barrier integrity. Moreover, a reduction of HIF-1α aggravated ventricular remodeling, which could be alleviated by LQF. Correspondingly, the circulating levels of intestinal permeability markers and BNP in HF patients were significantly decreased, and cardiac function markedly improved following LQF treatment. CONCLUSIONS: We demonstrated that LQF effectively protected cardiac function by preserving intestinal barrier integrity caused by ventricular remodeling, at least partially through upregulating HIF-1α expression.

Targeting regulatory T cells for cardiovascular diseases.

Cardiovascular diseases (CVDs) are the leading cause of death and disability worldwide. The CVDs are accompanied by inflammatory progression, resulting in innate and adaptive immune responses. Regulatory T cells (Tregs) have an immunosuppressive function and are one of the subsets of CD4+T cells that play a crucial role in inflammatory diseases. Whether using Tregs as a biomarker for CVDs or targeting Tregs to exert cardioprotective functions by regulating immune balance, suppressing inflammation, suppressing cardiac and vascular remodeling, mediating immune tolerance, and promoting cardiac regeneration in the treatment of CVDs has become an emerging research focus. However, Tregs have plasticity, and this plastic Tregs lose immunosuppressive function and produce toxic effects on target organs in some diseases. This review aims to provide an overview of Tregs' role and related mechanisms in CVDs, and reports on the research of plasticity Tregs in CVDs, to lay a foundation for further studies targeting Tregs in the prevention and treatment of CVDs.

Luhong Granules Prevent Ventricular Remodelling after Myocardial Infarction by Reducing the Metabolites TMAO and LPS of the Intestinal Flora.

BACKGROUND: Ventricular remodelling is a common pathological change at all stages of heart disease. Luhong granules are widely used in patients with chronic ventricular remodelling after myocardial infarction and can alleviate chest tightness, shortness of breath, and other symptoms. However, its effect on ventricular remodelling remains to be studied. PURPOSE: In this study, we investigated the effects of these granules on myocardial fibrosis in a rat model of myocardial infarction in vivo. METHODS: Male Wistar rats were randomly divided into four groups: the sham operation group, the acute myocardial infarction (AMI) group, the Luhong granule group, and the vancomycin group, with a sample size (n) of 10 rats in each group. The AMI model was established in all rats by ligation of the left anterior descending (LAD) coronary artery (the sham operation group did not undergo ligation). Luhong granules (0.5 ml·kg-1·d-1), vancomycin (0.075 g·ml-1·d-1), and 0.9% saline (5 ml·kg-1·d-1 for the sham operation and AMI groups) were administered orally for 6 weeks. Echocardiography was used to check cardiac structure and function. Myocardial and small intestinal tissue morphology was observed by haematoxylin and eosin (H&E) staining, and heart samples were stained with Masson's trichrome to analyse myocardial fibrosis. 16S rDNA sequencing was performed to detect changes in the gut flora. The level of trimethylamine N-oxide (TMAO) in plasma samples was quantified by stable isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS). RESULTS: H&E and Masson's trichrome staining of cardiac tissues showed that Luhong granules could partially reverse ventricular remodelling and improve intestinal barrier function (P < 0.05). Echocardiographic analysis showed that, compared with the AMI group, the left ventricular ejection fraction (LVEF) in the Luhong granule group was increased (P < 0.05). Stool sequencing and microbiological analysis showed changes in Bacteroidales, Alistipes, Phascolarctobacterium, etc., which can produce TMAO. We found that Luhong granules can reduce Bacteroidales, Alistipes, and Phascolarctobacterium at the genus level. The levels of TMAO and lipopolysaccharides (LPS) in plasma samples were reduced in the Luhong granule group (P < 0.05). CONCLUSIONS: Our results indicate that Luhong granules reduce TMAO and LPS levels in circulating blood by improving intestinal flora and intestinal barrier function to delay ventricular remodelling after myocardial infarction.