Rosuvastatin (RVS) is an excellent drug with anti-inflammatory and lipid-lowering properties in the academic and medical fields. However, this drug faces a series of challenges when used to treat atherosclerosis cause...Rosuvastatin (RVS) is an excellent drug with anti-inflammatory and lipid-lowering properties in the academic and medical fields. However, this drug faces a series of challenges when used to treat atherosclerosis caused by hyperhomocysteinemia (HHcy), including high oral dosage, poor targeting, and long-term toxic side effects. In this study, we applied nanotechnology to construct a biomimetic nano-delivery system, macrophage membrane (Møm)-coated RVS-loaded Prussian blue (PB) nanoparticles (MPR NPs), for improving the bioavailability and targeting capacity of RVS, specifically to the plaque lesions associated with HHcy-induced atherosclerosis. In vitro assays demonstrated that MPR NPs effectively inhibited the Toll-like receptor 4 (TLR4)/hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding and oligomerization domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) signaling pathways, reducing pyroptosis and inflammatory response in macrophages. Additionally, MPR NPs reversed the abnormal distribution of adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1)/ATP binding cassette transporter G1 (ABCA1)/ATP binding cassette transporter G1 (ABCG1) caused by HIF-1α, promoting cholesterol efflux and reducing lipid deposition. In vivo studies using apolipoprotein E knockout (ApoE^(−/−)) mice confirmed the strong efficacy of MPR NPs in treating atherosclerosis with favorable biosecurity, and the mechanism behind this efficacy is believed to involve the regulation of serum metabolism and the remodeling of gut microbes. These findings suggest that the synthesis of MPR NPs provides a promising nanosystem for the targeted therapy of HHcy-induced atherosclerosis.展开更多
Objective:The aim of this study is to assess the correlation between traditional cardiovascular risk factors and elevated plasma tHcy level in Nigerian hypertensive.Methods:Thirty-six hypertensive patients were recrui...Objective:The aim of this study is to assess the correlation between traditional cardiovascular risk factors and elevated plasma tHcy level in Nigerian hypertensive.Methods:Thirty-six hypertensive patients were recruited with 36 age and sex-matched controls.The age,sex and anthropometric measurements including height,weight and body mass index(BMI)were taken.Plasma total cholesterol,low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),triglycerides and tHcy were analyzed.The results of the two groups were compared.Results:The mean total cholesterol and LDL-C were significantly higher in the subjects than in the controls(P=0.01 and 0.03 respectively).On the other hand,means of HDL-C and triglycerides were not significantly different between the two groups(P=0.06 and 0.68 respectively).Mean total plasma tHcy was(12.95±4.9)μmol/L in hypertensive patients when compared with(11.29±3.6)μmol/L in the controls(P=0.09),however the mean tHcy was significantly higher in hypertensive patients who had stroke or myocardial infarction than those without these complications(one way Anova F=3.63,P=0.04).Significant positive correlation was seen between tHcy and systolic blood pressure,diastolic blood pressure,BMI and LDL-C.Conclusion:The study suggests that elevated plasma tHcy may predict occurrence of cardiovascular complications in hypertensive individuals.展开更多
BACKGROUND： Data indicate that the levels of serum homocysteine in depressive patients are higher than those in normal subjects. OBJECTIVE： To investigate the levels of serum homocysteine in patients with major depr...BACKGROUND： Data indicate that the levels of serum homocysteine in depressive patients are higher than those in normal subjects. OBJECTIVE： To investigate the levels of serum homocysteine in patients with major depressive disorder, to determine whether serum homocysteine levels differ with sex, family history, or drug treatment, and to compare depressive patients with normal subjects. DESIGN： Non-randomized concurrent control trial. SETTING： Mental Heath Center of Shandong Province. PARTICIPANTS： Forty in-patients （23 males and 17 females, 18-63 years old） with major depressive disorder were selected from the Mental Health Center of Shandong Province from January to October 2006. All selected patients met the depressive diagnostic standard of Chinese Classification of Mental Disorder （3^rd Edition, CCMD-3）, and total scores evaluated by the 17-item Hamilton Rating Scale for Depression （HRSD） were ≥ 20. Meanwhile, 36 healthy subjects （20 males and 16 females, 18-60 years old） were enrolled as controls; their total 17-item HRSD scores were ≤ 7. All selected subjects provided consent, and the study was approved by the local ethics committee. METHODS： Fasting venous blood （3 mL） was drawn in both groups at 8：00 in the morning. The levels of serum homocysteine were determined by a fluorescence polarization immunoassay （FPIA）. The 17-item HRSD was also compiled from the patients when entering groups. The higher the scores were, the more severe the depression was. Enumeration data for both groups were compared by Chi-square test, measurement data were compared by t-test, and correlations were detected using Pearson and Spearman correlation analysis. MAIN OUTCOME MEASURES： ① Levels of serum homocysteine; ② incidence of hyperhomocysteinemia （HHcy）; ③ correlation between HRSD17 scores and levels of serum homocysteine in depressive patients. RESULTS： Forty depressive patients and 36 control subjects were included in the final analysis without any loss of participants. ① Levels of serum homocysteine and HHcy detection rate： the levels of serum homocysteine in the depressive patients were significantly higher than those in the control group （t = 4.377, P=0.000）. Hhcy detection rates were 42% （17/40） and 10% （4/36） in depressive group and control group, respectively. There was a significant difference between two groups （x^2 = 10.912, P = 0.001）. In the depressive group, there were no differences in serum homocysteine levels between males and females, before and after treatment, or between patients with positive or negative family histories of depression （t = 0.217-0.520, P 〉 0.05）. ② Correlation analysis： the HRSD17 scores in the depressive group were positively correlated with levels of serum homocysteine （r = 0.724, P = 0.000）. CONCLUSION： ① The increase in serum homocysteine levels may play an important role in the pathogenic mechanism of depressive disorder. ② The higher the levels of serum homocysteine are, the more severe the depressive disorder is. ③ There are no significant differences in serum homocysteine levels between patients of different sex or family history, or before and after drug treatment, among depressive patients.展开更多
Increased plasma total homocysteine (tHcy) and high sensitivity C-reactive protein (hsCRP) levels are independent risk factors for cardiovascular disease.However, the predictive value of tHcy in combination with hsCRP...Increased plasma total homocysteine (tHcy) and high sensitivity C-reactive protein (hsCRP) levels are independent risk factors for cardiovascular disease.However, the predictive value of tHcy in combination with hsCRP in patients with stroke is not known.To determine the relationship between tHcy and hsCRP, we enrolled 291 patients with first-onset stroke (196 ischemic and 95 hemorrhagic).Plasma tHcy and hsCRP levels were measured and subsequent vascular events and deaths were determined over a 5-year period.Using the arbitrary cutoff for tHcy (【18 μmol/L and ≥18 μmol/L) and hsCRP (【1 mg/L, 1-3 mg/L and 】3 mg/L), the patients were divided into 6 groups.Survival analysis showed that the probability of death or new vascular events during a 5-year follow-up increased according to tHcy and hsCRP levels (P【0.01).The relative risk (RR) of death or new vascular events was 4.67 (95% CI, 1.96 to 11.14, P=0.001) in patients with high tHcy (≥18 μmol/L) and hsCRP (】3 mg/L) compared with those with low tHcy (【18 μmol/L) and hsCRP (【1 mg/L).The increased tHcy level (≥18 μmol/L) combined with increased hsCRP level (】3 mg/L) was still significantly associated with the risk of death or new vascular events (RR, 4.10, 95% CI, 1.61 to 10.45, P=0.003) even when adjusted for other risk factors at inclusion.The combination of increased tHcy and hsCRP levels had a stronger predictive value than increased hsCRP alone or increased tHcy level alone.Further studies are required to evaluate the potential decrease in risks associated with lowering both Hcy and hsCRP levels in patients that present with both increased tHcy and hsCRP.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.:U21A20343,82160088,81870225,81870332,81700404,82271626,and 82260088)the Natural Science Foundation of Ningxia Autonomous Region,China(Grant Nos.:2020AAC02021,2020AAC02038,and 2022AAC05025)+5 种基金the Key Research and Development Projects in Ningxia Autonomous Region,China(Grant Nos.:2020BFH02003,2021BEG02033,2020BEG03008,and 2022BFH02013)the Basic Scientific Research Operating Expenses from the Public Welfare Research Institutes at the Central Level of the Chinese Academy of Medical Sciences,China(Grant No.:2019PT330002)the Ningxia Science and Technology Leading Talent Project,China(Grant No.:KJT2017007)the Natural Science Foundation of Hunan Province,China(Grant No.:2022JJ40698)the School-level Special Talent Launching Project of Ningxia Medical University,China(Grant No.:XT2018015)the Open Bidding for Selecting the Best Candidates Program of Ningxia Medical University,China(Grant No.:XJKF230106).
文摘Rosuvastatin (RVS) is an excellent drug with anti-inflammatory and lipid-lowering properties in the academic and medical fields. However, this drug faces a series of challenges when used to treat atherosclerosis caused by hyperhomocysteinemia (HHcy), including high oral dosage, poor targeting, and long-term toxic side effects. In this study, we applied nanotechnology to construct a biomimetic nano-delivery system, macrophage membrane (Møm)-coated RVS-loaded Prussian blue (PB) nanoparticles (MPR NPs), for improving the bioavailability and targeting capacity of RVS, specifically to the plaque lesions associated with HHcy-induced atherosclerosis. In vitro assays demonstrated that MPR NPs effectively inhibited the Toll-like receptor 4 (TLR4)/hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding and oligomerization domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) signaling pathways, reducing pyroptosis and inflammatory response in macrophages. Additionally, MPR NPs reversed the abnormal distribution of adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1)/ATP binding cassette transporter G1 (ABCA1)/ATP binding cassette transporter G1 (ABCG1) caused by HIF-1α, promoting cholesterol efflux and reducing lipid deposition. In vivo studies using apolipoprotein E knockout (ApoE^(−/−)) mice confirmed the strong efficacy of MPR NPs in treating atherosclerosis with favorable biosecurity, and the mechanism behind this efficacy is believed to involve the regulation of serum metabolism and the remodeling of gut microbes. These findings suggest that the synthesis of MPR NPs provides a promising nanosystem for the targeted therapy of HHcy-induced atherosclerosis.
文摘Objective:The aim of this study is to assess the correlation between traditional cardiovascular risk factors and elevated plasma tHcy level in Nigerian hypertensive.Methods:Thirty-six hypertensive patients were recruited with 36 age and sex-matched controls.The age,sex and anthropometric measurements including height,weight and body mass index(BMI)were taken.Plasma total cholesterol,low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),triglycerides and tHcy were analyzed.The results of the two groups were compared.Results:The mean total cholesterol and LDL-C were significantly higher in the subjects than in the controls(P=0.01 and 0.03 respectively).On the other hand,means of HDL-C and triglycerides were not significantly different between the two groups(P=0.06 and 0.68 respectively).Mean total plasma tHcy was(12.95±4.9)μmol/L in hypertensive patients when compared with(11.29±3.6)μmol/L in the controls(P=0.09),however the mean tHcy was significantly higher in hypertensive patients who had stroke or myocardial infarction than those without these complications(one way Anova F=3.63,P=0.04).Significant positive correlation was seen between tHcy and systolic blood pressure,diastolic blood pressure,BMI and LDL-C.Conclusion:The study suggests that elevated plasma tHcy may predict occurrence of cardiovascular complications in hypertensive individuals.
文摘BACKGROUND： Data indicate that the levels of serum homocysteine in depressive patients are higher than those in normal subjects. OBJECTIVE： To investigate the levels of serum homocysteine in patients with major depressive disorder, to determine whether serum homocysteine levels differ with sex, family history, or drug treatment, and to compare depressive patients with normal subjects. DESIGN： Non-randomized concurrent control trial. SETTING： Mental Heath Center of Shandong Province. PARTICIPANTS： Forty in-patients （23 males and 17 females, 18-63 years old） with major depressive disorder were selected from the Mental Health Center of Shandong Province from January to October 2006. All selected patients met the depressive diagnostic standard of Chinese Classification of Mental Disorder （3^rd Edition, CCMD-3）, and total scores evaluated by the 17-item Hamilton Rating Scale for Depression （HRSD） were ≥ 20. Meanwhile, 36 healthy subjects （20 males and 16 females, 18-60 years old） were enrolled as controls; their total 17-item HRSD scores were ≤ 7. All selected subjects provided consent, and the study was approved by the local ethics committee. METHODS： Fasting venous blood （3 mL） was drawn in both groups at 8：00 in the morning. The levels of serum homocysteine were determined by a fluorescence polarization immunoassay （FPIA）. The 17-item HRSD was also compiled from the patients when entering groups. The higher the scores were, the more severe the depression was. Enumeration data for both groups were compared by Chi-square test, measurement data were compared by t-test, and correlations were detected using Pearson and Spearman correlation analysis. MAIN OUTCOME MEASURES： ① Levels of serum homocysteine; ② incidence of hyperhomocysteinemia （HHcy）; ③ correlation between HRSD17 scores and levels of serum homocysteine in depressive patients. RESULTS： Forty depressive patients and 36 control subjects were included in the final analysis without any loss of participants. ① Levels of serum homocysteine and HHcy detection rate： the levels of serum homocysteine in the depressive patients were significantly higher than those in the control group （t = 4.377, P=0.000）. Hhcy detection rates were 42% （17/40） and 10% （4/36） in depressive group and control group, respectively. There was a significant difference between two groups （x^2 = 10.912, P = 0.001）. In the depressive group, there were no differences in serum homocysteine levels between males and females, before and after treatment, or between patients with positive or negative family histories of depression （t = 0.217-0.520, P 〉 0.05）. ② Correlation analysis： the HRSD17 scores in the depressive group were positively correlated with levels of serum homocysteine （r = 0.724, P = 0.000）. CONCLUSION： ① The increase in serum homocysteine levels may play an important role in the pathogenic mechanism of depressive disorder. ② The higher the levels of serum homocysteine are, the more severe the depressive disorder is. ③ There are no significant differences in serum homocysteine levels between patients of different sex or family history, or before and after drug treatment, among depressive patients.
基金supported in part by funds from a national research project of China (Program 863) (No.2006-AA02A406)a project of the Ministry of Education of China+1 种基金a project of the National Natural Sciences Foundation of China (No.30540087)a national basic research program of China (Program 973) (No.2007CB512004)
文摘Increased plasma total homocysteine (tHcy) and high sensitivity C-reactive protein (hsCRP) levels are independent risk factors for cardiovascular disease.However, the predictive value of tHcy in combination with hsCRP in patients with stroke is not known.To determine the relationship between tHcy and hsCRP, we enrolled 291 patients with first-onset stroke (196 ischemic and 95 hemorrhagic).Plasma tHcy and hsCRP levels were measured and subsequent vascular events and deaths were determined over a 5-year period.Using the arbitrary cutoff for tHcy (【18 μmol/L and ≥18 μmol/L) and hsCRP (【1 mg/L, 1-3 mg/L and 】3 mg/L), the patients were divided into 6 groups.Survival analysis showed that the probability of death or new vascular events during a 5-year follow-up increased according to tHcy and hsCRP levels (P【0.01).The relative risk (RR) of death or new vascular events was 4.67 (95% CI, 1.96 to 11.14, P=0.001) in patients with high tHcy (≥18 μmol/L) and hsCRP (】3 mg/L) compared with those with low tHcy (【18 μmol/L) and hsCRP (【1 mg/L).The increased tHcy level (≥18 μmol/L) combined with increased hsCRP level (】3 mg/L) was still significantly associated with the risk of death or new vascular events (RR, 4.10, 95% CI, 1.61 to 10.45, P=0.003) even when adjusted for other risk factors at inclusion.The combination of increased tHcy and hsCRP levels had a stronger predictive value than increased hsCRP alone or increased tHcy level alone.Further studies are required to evaluate the potential decrease in risks associated with lowering both Hcy and hsCRP levels in patients that present with both increased tHcy and hsCRP.
