Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in

Objective: To evaluate the efficacy and safety of ivabradine for the treatment of Chinese patients with chronic heart failure based on the Chinese subgroup data of the systolic heart failure treatment with the I_f inhibitor ivabradine trial (SHIFT). Method: A total of 6 558 stable outpatients who presented symptoms of heart failure, with a left ventricular ejection fraction (LVEF) ≤35%, sinus rhythms with a heart rate ≥70 bpm participated in the randomized, double-blind, placebo-controlled, international multicenter clinical study.The subset of Chinese patients with heart rate ≥75 bpm was enrolled in the post-hoc subgroup analyses.Patients were randomly allocated by computer-generated assignment through a telephone interactive voice response system to ivabradine group (starting dose 5 mg bid, which was then uptitrated to the maximum 7.5 mg bid) or matched placebo group.The clinical baseline characteristics of participants were obtained and analyzed.The primary outcome endpoint was a composite endpoint of cardiovascular death or hospitalization resulting from worsening HF.The primary safety endpoint included total incidence of adverse events during the study, bradycardia, and adverse visual reaction (phosphenes). Results: A total of 49 Chinese centers enrolled a total of 225 patients with chronic heart failure, of whom, 106 patients were randomized to the ivabradine group and the other 119 patients to the placebo group, and the mean follow-up time was (15.6±5.1) months.By the end of the study, mean heart rate (71.0 bpm vs. 80.3 bpm, P<0.05) and incidence of the primary endpoint events (18.9% (20/106) vs. 31.9%(38/119), HR=0.56, 95%CI 0.33-0.97, P=0.039) were significantly lower, while the percentage of patients with improvement in heart functional class NYHA (53.8% (56/106) vs. 34.5% (41/119), P=0.006 1) was significantly higher in the ivabradine group than in the placebo group.The total number of adverse events (129 events, 49.6% PY) in the ivabradine group was lower than that in the placebo group (203 events, 50.8% PY). In the ivabradine group and the placebo group, there were respectively 2 patients (1.9%) and 0 patients experienced bradycardia, 3 patients (2.9%) and 1 patient (0.8%) experienced adverse visual reaction (phosphenes). Conclusions: Ivabradine significantly reduced heart rate and improved the clinical outcomes and NYHA function class in Chinese patients with chronic heart failure, these beneficial effects are achieved without inducing remarkable adverse reactions.The results of Chinese subgroup analysis were thus consistent with the overall results of the SHIFT study. Clinical Trial Registry International standard randomized controlled trials registry, ISRCTN 70429960.

OBJECTIVETo investigate the pathologies of aortic root atherosclerotic lesion in uremic apoE-/- mice and explore the effect of serum from patients with chronic renal insufficiency (CRI) and the uremic toxin, indoxyl sulfate (IS), on the expression of cholesterol transporting receptors and lipid accumulation in macrophages in vitro.

METHODSThe uremic apoE-/- mouse model was established by surgical operation. Frozen sections of the aortic root were collected from uremic apoE-/- mice, sham-operated apoE-/- mice and C57BL/6J mice and stained with oil red O to calculate the relative area of atherosclerotic plaque. Murine macrophage RAW264.7 cell line was treated for 12 h with different concentrations of IS or serum samples from CRI patients and healthy individuals, and the mRNA expressions of cholesterol transporting receptors (SR-A1, CD36, ABCA1, ABCG1 and SR-B1) were detected. After treatment for 24 h, the cells were induced into foam cells to determine lipid contents using oil red O staining.

RESULTSThe relative area of the atherosclerotic plaques in the aortic root increased significantly in uremic apoE-/- mice compared with that in sham-operated apoE-/- mice. CRI serum (5%) and IS (250 µmol/L) obviously increased the mRNA expression of CD36 and lipid accumulation in the macrophages, but did not affect the mRNA expression of other cholesterol transporting receptors.

CONCLUSIONCRI can accelerate the progression of atherosclerosis through the mechanism that IS in CRI serum promotes lipid accumulation in macrophages by enhancing the mRNA expression of CD36, which contributes to the formation of foam cells.

Animals ; Apolipoproteins E ; Cell Line ; Foam Cells ; chemistry ; Humans ; Indican ; pharmacology ; Lipids ; chemistry ; Macrophages ; chemistry ; Mice ; Mice, Inbred C57BL ; Plaque, Atherosclerotic ; pathology ; Renal Insufficiency, Chronic ; blood

Objective To explore the method of oleic acid two strike to build a better clinical pathophysiology of acute lung injury animal model state.Methods The 60 male and healthy Sprague-Dawley rats, weighing 180 ～ 220g.According to the time of purchase.No.1, 2, 3 The order No.60, Each number, were randomly divided into 3 groups: normal control group(20 rats) : intravenous injection of normal saline 0.07ml/kg, an hour after intravenous injection of saline 0.03 ml/kg.The traditional group(20 rats) : intravenous injection of oleic acid 0.l ml/kg.The model group(20 rats) : intravenous injection of oleic acid 0.07 ml/kg, one hour after intravenous injection of oleic acid 0.03 ml/kg.Close observation of vital signs of breathing and Hemodynamicsin rats.Stable operation of 30 min, Each operation is stable after 30 minutes of measuring arterial blood gas, lung water content, the change degree evaluation of early lung injury of lung tissue pathology.Through the analysis of arterial blood gas, lung water content, HE stained pathological changes of lung tissue in Smith scoring method to determine the degree of lung injury in rats, to evaluate whether the model was successfully established.Results There are 5 rats died after a sharp drop in blood pressure of oleic acid used in traditional group rats, the changes of hemodynamics of traditional group compared with model group were severe, especially in the 5 ～ 30min after injection of oleic acid.The model group was no death, intravenous injection of oleic acid(0.1 ml/kg) from 7 to 8 min after respiratory frequency rats increased gradually, difficulty in breathing, endotracheal see pink frothy sputum.After 1 h pumping and arterial blood gas results showed that pH (7.17 ± 0.15) PaO2, (41.85 ± 8.16) mmHg was significantly lower than that of normal group(P ＜ 0.01) , oxygenation index (PaO2/FiO2) ≤ 300 mmHg, met the diagnostic criteria of acute lung injury, the moisture content(P ＜ 0.05), according to the Smith score, pathological model group compared with normal group significantly increased(P ＜ 0.01).Conclusion Two hit the body can produce severe inflammatory reaction of lung and lasting, build a close clinical pathophysiology of acute lung injury animal model successfully state.Meet the pathophysiological clinical change of acute lung injury, and can be used for basic and clinical research of acute lung injury in infants.

ABSTRACT:Objective To observe the effect of curcumin on RAW264.7 macrophages induced with LPS and IFNγ(M1)and the mechanisms involved.Methods Curcumin of different concentrations (6.25 μmol/L,12.5μmol/L and 25 μmol/L)was used to treat RAW264.7 macrophages induced with LPS and IFNγ(M1)for 12 h,and RAW264.7 macrophages induced with LPS and IFNγ(M1)were incubated with 20μmol/L GW9662 and 25 μmol/L curcumin for 12 h.Using Real-time PCR,ELISA and Western blotting analysis,we examined the expressions of IL-1β,IL-6,PPARγand phenotype markers M2 (KLF4,FIZZ1,and MGL1 )and the expressions of KLF4 and FIZZ1 when PPARγwas inhibited.Results Curcumin of different concentrations all could inhibit the expressions of IL-1βand IL-6 in RAW264.7 macrophages induced with LPS and IFNγ(M1).Curcumin of different concentra-tions could upregulate the expression of M2 markers (KLF4,FIZZ1 and MGL1)and PPARγin RAW264.7 macro-phages induced with LPS and IFNγ(M1).When M1 macrophages were incubated with curcumin and GW9662,the expression of the M2 phenotype markers was reduced.Conclusion Curcumin polarized the M1 phenotype macro-phages derived from RAW264.7 macrophages to become M2 phenotype through activating PPARγ.

Objective To investigate the pathologies of aortic root atherosclerotic lesion in uremic apoE-/-mice and explore the effect of serum from patients with chronic renal insufficiency (CRI) and the uremic toxin, indoxyl sulfate (IS), on the expression of cholesterol transporting receptors and lipid accumulation in macrophages in vitro. Methods The uremic apoE-/-mouse model was established by surgical operation. Frozen sections of the aortic root were collected from uremic apoE-/-mice, sham-operated apoE-/- mice and C57BL/6J mice and stained with oil red O to calculate the relative area of atherosclerotic plaque. Murine macrophage RAW264.7 cell line was treated for 12 h with different concentrations of IS or serum samples from CRI patients and healthy individuals, and the mRNA expressions of cholesterol transporting receptors (SR-A1, CD36, ABCA1, ABCG1 and SR-B1) were detected. After treatment for 24 h, the cells were induced into foam cells to determine lipid contents using oil red O staining. Results The relative area of the atherosclerotic plaques in the aortic root increased significantly in uremic apoE-/- mice compared with that in sham-operated apoE-/- mice. CRI serum (5%) and IS (250 μmol/L) obviously increased the mRNA expression of CD36 and lipid accumulation in the macrophages, but did not affect the mRNA expression of other cholesterol transporting receptors. Conclusion CRI can accelerate the progression of atherosclerosis through the mechanism that IS in CRI serum promotes lipid accumulation in macrophages by enhancing the mRNA expression of CD36, which contributes to the formation of foam cells.

Objective To investigate the pathologies of aortic root atherosclerotic lesion in uremic apoE-/-mice and explore the effect of serum from patients with chronic renal insufficiency (CRI) and the uremic toxin, indoxyl sulfate (IS), on the expression of cholesterol transporting receptors and lipid accumulation in macrophages in vitro. Methods The uremic apoE-/-mouse model was established by surgical operation. Frozen sections of the aortic root were collected from uremic apoE-/-mice, sham-operated apoE-/- mice and C57BL/6J mice and stained with oil red O to calculate the relative area of atherosclerotic plaque. Murine macrophage RAW264.7 cell line was treated for 12 h with different concentrations of IS or serum samples from CRI patients and healthy individuals, and the mRNA expressions of cholesterol transporting receptors (SR-A1, CD36, ABCA1, ABCG1 and SR-B1) were detected. After treatment for 24 h, the cells were induced into foam cells to determine lipid contents using oil red O staining. Results The relative area of the atherosclerotic plaques in the aortic root increased significantly in uremic apoE-/- mice compared with that in sham-operated apoE-/- mice. CRI serum (5%) and IS (250 μmol/L) obviously increased the mRNA expression of CD36 and lipid accumulation in the macrophages, but did not affect the mRNA expression of other cholesterol transporting receptors. Conclusion CRI can accelerate the progression of atherosclerosis through the mechanism that IS in CRI serum promotes lipid accumulation in macrophages by enhancing the mRNA expression of CD36, which contributes to the formation of foam cells.

OBJECTIVETo examine the changes in the expression of pro-inflammatory and anti-inflammatory cytokines in the peripheral blood mononuclear cells (PBMCs) and elucidate the inflammatory status of apparently healthy subjects.

METHODSPeripheral blood samples (5 ml) were collected after fasting for more than 8 h from 14 healthy control subjects and 14 apparently healthy subjects with elevated serum high-sensitivity CRP (hsCRP) level (≥ 2.0 mg/L). PBMCs were separated by Ficoll density gradient centrifugation and the total RNA was extracted for real-time quantitative PCR analysis of the inflammatory cytokines, and plasma was separated for ELISA analysis of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) expressions.

RESULTSThe gene expressions of TNF-α and MCPIP were significantly increased in PBMCs of apparently healthy subjects, while IL-6 and MCP-1 only showed slight elevations; IL-10 expression in PBMCs decreased significantly in apparently healthy subjects as compared to that in the control group. The results of ELISA showed significantly elevated TNF-α level without significant changes of plasma IL-6 level in apparently healthy subjects.

CONCLUSIONIn apparently healthy subjects with normal lipid levels, chronic low-grade inflammation has occurred shown by elevated expressions of the pro-inflammatory cytokines and lowered expressions of the anti-inflammatory cytokines.

Enzyme-Linked Immunosorbent Assay ; Gene Expression ; Healthy Volunteers ; Humans ; Inflammation ; immunology ; Interleukin-10 ; blood ; Interleukin-6 ; blood ; Leukocytes, Mononuclear ; immunology ; Tumor Necrosis Factor-alpha ; blood

Objective To examine the changes in the expression of pro-inflammatory and anti-inflammatory cytokines in the peripheral blood mononuclear cells (PBMCs) and elucidate the inflammatory status of apparently healthy subjects. Methods Peripheral blood samples (5 ml) were collected after fasting for more than 8 h from 14 healthy control subjects and 14 apparently healthy subjects with elevated serum high-sensitivity CRP (hsCRP) level (≥2.0 mg/L). PBMCs were separated by Ficoll density gradient centrifugation and the total RNA was extracted for real-time quantitative PCR analysis of the inflammatory cytokines, and plasma was separated for ELISA analysis of interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α) expressions. Results The gene expressions of TNF-α and MCPIP were significantly increased in PBMCs of apparently healthy subjects, while IL-6 and MCP-1 only showed slight elevations;IL-10 expression in PBMCs decreased significantly in apparently healthy subjects as compared to that in the control group. The results of ELISA showed significantly elevated TNF-α level without significant changes of plasma IL-6 level in apparently healthy subjects. Conclusion In apparently healthy subjects with normal lipid levels, chronic low-grade inflammation has occurred shown by elevated expressions of the pro-inflammatory cytokines and lowered expressions of the anti-inflammatory cytokines.

Objective To examine the changes in the expression of pro-inflammatory and anti-inflammatory cytokines in the peripheral blood mononuclear cells (PBMCs) and elucidate the inflammatory status of apparently healthy subjects. Methods Peripheral blood samples (5 ml) were collected after fasting for more than 8 h from 14 healthy control subjects and 14 apparently healthy subjects with elevated serum high-sensitivity CRP (hsCRP) level (≥2.0 mg/L). PBMCs were separated by Ficoll density gradient centrifugation and the total RNA was extracted for real-time quantitative PCR analysis of the inflammatory cytokines, and plasma was separated for ELISA analysis of interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α) expressions. Results The gene expressions of TNF-α and MCPIP were significantly increased in PBMCs of apparently healthy subjects, while IL-6 and MCP-1 only showed slight elevations;IL-10 expression in PBMCs decreased significantly in apparently healthy subjects as compared to that in the control group. The results of ELISA showed significantly elevated TNF-α level without significant changes of plasma IL-6 level in apparently healthy subjects. Conclusion In apparently healthy subjects with normal lipid levels, chronic low-grade inflammation has occurred shown by elevated expressions of the pro-inflammatory cytokines and lowered expressions of the anti-inflammatory cytokines.