[Beneficial effects and related mechanism of hawthorn leaves flavonoids on cardiac function in rats with acute myocardial infarction].

Objective: To explore the effect and related regulatory mechanism of hawthorn leaf flavonoids (FHL) on cardiac function in rats with acute myocardial infarction (AMI). Methods: Sixty SPF male Sprague-Dawley rats (9-week-old, weighing 300-350 g) were used in this study. Ten rats were assigned to sham operation group, and the remaining 50 rats were used to establish the AMI model with coronary artery ligation method, AMI was successfully established in 36 rats. AMI rats were randomly divided into AMI group and FHL low-, medium-, and high-dose groups (n=9 for each group). Rats received intraperitoneal injection (10 ml·kg-1·day-1) with physiological saline and FHL solution with concentrations of 0.3, 0.6, and 1.2 mg/ml, respectively for 4 consecutive weeks. Echocardiography was performed at the end of experiments. Left ventricular end diastolic diameter (LVEDD), left ventricular end diastolic anterior wall thickness (LAWD), left ventricular ejection fraction (LVEF) and left ventricular end diastolic pressure (LVEDP) were measured. Then the rats were sacrificed under deep anesthesia, and the left ventricular anterior wall tissue was used for pathological examinations by hematoxylin-eosin (HE) staining. Other myocardial tissue was used for in situ terminal transferase labeling (TUNEL) staining, and the apoptosis rate of cardiomyocytes was calculated. The myocardial cell apoptosis rate, the mRNA, and protein expressions of phosphatidylinositol 3ß-kinase (PI3K), protein kinase B (Akt), glycogen synthetase kinase-3 (GSK3ß), cyclin D1 and the protein expressions of p-Akt and p-GSK3ß were detected by real-time fluorescent quantitative PCR (RT-qPCR) and Western blot respectively. Results: Compared with sham operation group, the LVEDD and LVEDP of the rats in AMI group and FHL low-, medium-and high-dose groups were increased, and the LAWD and LVEF were reduced (all P<0.05). Compared with AMI group, LVEDD and LVEDP were reduced, and LAWD and LVEF were increased in FHL low-, medium-and high-dose groups (all P<0.05). LVEDD and LVEDP decreased, and LAWD and LVEF increased in proportion to the increase of FHL dose (all P<0.05). LVEDD and LAWD values were similar between FHL low-dose and medium-dose groups (both P>0.05). HE staining results evidenced necrotic myocardial tissue, together with disordered arrangement of myocardial fibers, and a large number of inflammatory cells infiltrated in the myocardial tissue in AMI group. The myocardial damage of rats in FHL low-, medium-, and high-dose groups was less than that of AMI group. The myocardial fibers were arranged neatly, but there were still partial breaks and a small amount of inflammatory cell infiltration in the myocardial tissue and there were scattered islands of normal myocardial tissue in the infarct area of these groups. Among them, myocardial damage was the least in FHL high-dose group. The results of TUNEL staining showed that compared with AMI group, the apoptosis rate of myocardial cells was significantly reduced in FHL low-, medium-, and high-dose groups (all P<0.001), but was still higher than that in sham operation group (all P<0.001). Myocardial cell apoptosis rate decreased in proportion with increasing FHL dose (P<0.05). The RT-qPCR results showed that compared with AMI group, the expression levels of PI3K and cyclin D1 mRNA were significantly upregulated in the myocardial tissue of rats in FHL low-, medium-, and high-dose groups, but still lower than those in sham operation group (all P<0.05), and PI3K and cyclin D1 mRNA expression levels increased with the increase dose of FHL (P<0.05). Western blot results showed that compared with AMI group, the expression levels of PI3K, p-Akt, p-GSK3ß, and cyclin D1 were significantly upregulated in the myocardial tissue of rats in FHL low-, medium-, and high-dose groups, but still lower than those in sham operation group (all P<0.05), and the protein expression levels of PI3K, p-Akt, p-GSK3ß, and cyclin D1 increased in proportion with the increase dose of FHL (all P<0.05). Conclusion: FHL can effectively improve cardiac function in rats with AMI, and the beneficial effects may be partly mediated through activating PI3K/GSK3ß/cyclin D1 signaling pathway.

Prevalence of vitamin D insufficiency among adolescents and its correlation with bone parameters using high-resolution peripheral quantitative computed tomography.

UNLABELLED: Vitamin D deficiency and insufficiency are highly prevalent among adolescents in Hong Kong, which is a sub-tropical city with ample sunshine. Vitamin D level is significantly correlated with key bone density and bone quality parameters. Further interventional studies are warranted to define the role of vitamin D supplementation for improvement of bone health among adolescents. INTRODUCTION: The relationship between bone quality parameters and vitamin D (Vit-D) status remains undefined among adolescents. The aims of this study were to evaluate Vit-D status and its association with both bone density and bone quality parameters among adolescents. METHODS: Three hundred thirty-three girls and 230 boys (12-16 years old) with normal health were recruited in summer and winter separately from local schools. Serum 25(OH) Vit-D level, bone density and quality parameters by Dual Energy X-ray Absorptiometry (DXA) and High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT), dietary calcium intake, and physical activity level were assessed. RESULTS: Sixty-four point seven percent and 11.4 % of subjects were insufficient [25 ≤ 25(OH)Vit-D ≤ 50 nmol/L] and deficient [25(OH)Vit-D < 25 nmol/L] in Vit-D, respectively. The mean level of serum 25(OH)Vit-D in summer was significantly higher than that in winter (44.7 ± 13.6 and 35.9 ± 12.6 nmol/L, respectively) without obvious gender difference. In girls, areal bone mineral density (aBMD) and bone mineral content (BMC) of bilateral femoral necks, cortical area, cortical thickness, total volumetric bone mineral density (vBMD), and trabecular thickness were significantly correlated with 25(OH)Vit-D levels. In boys, aBMD of bilateral femoral necks, BMC of the dominant femoral neck, cortical area, cortical thickness, total vBMD, trabecular vBMD, BV/TV, and trabecular separation were significantly correlated with 25(OH)Vit-D levels. CONCLUSION: Vit-D insufficiency was highly prevalent among adolescents in Hong Kong with significant correlation between Vit-D levels and key bone density and bone quality parameters being detected in this study. Given that this is a cross-sectional study and causality relationship cannot be inferred, further interventional studies investigating the role of Vit-D supplementation on improving bone health among adolescents are warranted.

Abnormal Bone Mechanical and Structural Properties in Adolescent Idiopathic Scoliosis: A Study with Finite Element Analysis and Structural Model Index.

Previous studies found adolescent idiopathic scoliosis (AIS) is associated with low bone mineral density (BMD) and abnormal bone quality, whilst the association between AIS and their bone strength is unknown. From high-resolution peripheral quantitative computed tomography-generated images, bone mechanical properties can be evaluated with finite element analysis (FEA), and trabecular rod-plate configuration related to trabecular bone strength can be quantified by structure model index (SMI). This study aimed to compare trabecular configuration and bone mechanical properties between AIS and the controls. 95 AIS girls aged 12-14 years and 97 age- and gender-matched normal controls were recruited. Bilateral femoral necks and non-dominant distal radius were scanned by dual-energy X-ray absorptiometry for areal BMD and HR-pQCT for SMI and FEA, respectively. Subjects were further classified into osteopenic and non-osteopenic group based on their areal BMD. Bone mechanical properties (stiffness, failure load and apparent modulus) were calculated using FEA. Linear regression model was used for controlling age, physical activity and calcium intake. AIS was associated with lower failure load and apparent modulus after adjusting for age, whereas AIS was associated with lower apparent modulus after adjusting for all confounders. Osteopenic AIS was associated with more rod-like trabeculae when compared with non-osteopenic AIS, whereas no difference was detected between osteopenic and non-osteopenic controls. This might be the result of abnormal regulation and modulation of bone metabolism and bone modelling and remodelling in AIS which will warrant future studies with a longitudinal design to determine the significance of micro-architectural abnormalities in AIS.

Age-related differences in volumetric bone mineral density, microarchitecture, and bone strength of distal radius and tibia in Chinese women: a high-resolution pQCT reference database study.

UNLABELLED: In a cohort of 393 Chinese women, by using high-resolution peripheral quantitative computed tomography (HR-pQCT), we found that significant cortical bone loss occurred after midlife. Prominent increase in cortical porosity began at the fifth decade but reached a plateau before the sixth decade. Trabecular bone loss was already evident in young adulthood and continued throughout life. INTRODUCTION: This study aimed to investigate age-related differences in volumetric bone mineral density (vBMD), microarchitecture, and estimated bone strength at peripheral skeleton in Chinese female population. METHODS: In a cross-sectional cohort of 393 Chinese women aged 20-90 years, we obtained vBMD, microarchtecture, and micro-finite element-derived bone strength at distal radius and tibia using HR-pQCT. RESULTS: The largest predictive age-related difference was found for cortical porosity (Ct.Po) which showed over four-fold and two-fold differences at distal radius and tibia, respectively, over the adulthood. At both sites, cortical bone area, vBMD, and thickness showed significant quadratic association with age with significant decrease beginning after midlife. Change of Ct.Po became more prominent between age of 50 and 57 (0.26 %/year at distal radius, 0.54 %/year at distal tibia, both p ≤ 0.001) but thereafter, reached a plateau (0.015 and 0.028 %/year, both p > 0.05). In contrast, trabecular vBMD and microarchitecture showed linear association with age with significant deterioration observed throughout adulthood. Estimated age of peak was around age of 20 for trabecular vBMD and microarchitecture and Ct.Po and age of 40 for cortical vBMD and microarchitecture. Estimated stiffness and failure load peaked at mid-30s at the distal radius and at age 20 at distal tibia. CONCLUSIONS: Age-related differences in vBMD and microarchitecture in Chinese women differed by bone compartments. Significant cortical bone loss occurred after midlife. Prominent increase in Ct.Po began at the fifth decade but appeared to be arrested before the sixth decade. Loss of trabecular bone was already evident in young adulthood and continued throughout life.