Homocysteine ameliorates the endothelium-independent hypoxic vasoconstriction via the suppression of phosphatidylinositol 3-kinase/Akt pathway in porcine coronary arteries.

OBJECTIVE: Endothelium-independent coronary vasoconstriction induced by continuous hypoxia contributes to the development of ischemic heart diseases. Acute elevation of homocysteine (Hcy) has a potent of vasodilation. The present study aims to investigate the role of Hcy in endothelium-independent hypoxic coronary vasoconstriction and its underlying mechanisms. METHODS AND RESULTS: Vessel tension of isolated porcine coronary arteries was measured by organ chamber study and the protein expression were detected by western blot. A sustained contraction of porcine coronary artery was induced when exposed to prolonged hypoxia for more than 15 min, which was significantly reduced by Hcy in a dose-dependent manner but not affected by cysteine or N-acetyl-l-cysteine. Phosphorylated myosin light chain (MLC-p) at Ser19 was decreased when exposure to hypoxia for 15 min, and could be reversed by prolonged hypoxia for 30 and 60 min. The recovery of MLC-p at Ser19 by hypoxia for more than 30 min could be abolished by Hcy. The protein levels of phosphorylated Akt at Ser473 and phosphorylated P85 at Tyr508 were decreased by Hcy in normoxia, and were also reduced exposure to hypoxia for 15 min and then augmented by prolonged hypoxia for more than 30 min, which could be prevented by Hcy. The protein level of P110α was not affected by Hcy or prolonged hypoxia. CONCLUSIONS: This study demonstrates that Hcy can ameliorate the endothelium-independent hypoxic coronary vasoconstriction, in which the inhibition of PI3K/Akt signaling pathway may be involved.

Omega-3 PUFA ameliorates hyperhomocysteinemia-induced hepatic steatosis in mice by inhibiting hepatic ceramide synthesis.

Hyperhomocysteinemia (HHcy) is a key risk factor in hepatic steatosis. In this study, we applied a metabolomic approach to investigate the changes in the metabolite profile due to HHcy-induced hepatic steatosis and the effects of omega-3 PUFA (polyunsaturated fatty acid) supplementation in mice. HHcy was induced in mice by giving DL-Hcy (1.8 g/L) in drinking water for 6 weeks, then the mice were sacrificed, and the metabolic profiles of the liver and plasma were analyzed through UPLC-ESI-QTOFMS-based lipidomics. Hepatic triglycerides and cholesterol were further assayed. The expression of ceramide metabolism-related genes was measured by quantitative PCR. Compared with control mice, HHcy mice exhibited hepatic steatosis with a notable increase in ceramide-related metabolites and subsequent upregulation of ceramide synthesis genes such as Sptlc3, Degs2, Cer4 and Smpd4. Omega-3 PUFA was simultaneously administered in HHcy mice through chow diet containing 3.3% omega-3 PUFA supplement for 6 weeks, which significantly ameliorated Hcy-induced hepatic steatosis. The decrease in hepatic lipid accumulation was mainly due to reduced hepatic levels of ceramides, which was partly the result of the lower expression of ceramide synthesis genes, Sptlc3 and Degs2. Similar beneficial effects of DHA were observed in Hcy-stimulated primary hepatocytes in vitro. In summary, Hcy-induced ceramide elevation in hepatocytes might contribute to the development of hepatic steatosis. Furthermore, downregulation of ceramide levels through omega-3 PUFA supplementation ameliorates hepatic lipid accumulation. Thus, ceramide is a potential therapeutic target for the treatment of hepatic steatosis.

Longitudinal changes in mandibular arch posterior space in adolescents with normal occlusion.

INTRODUCTION: The purpose of this study was to investigate the changes of available mandibular space in the posterior dental arch of teenagers from 13 to 18 years old. METHODS: Longitudinal cephalograms of 28 adolescents (13 boys, 15 girls) with normal occlusion, selected from among 901 candidates, were taken annually from 13 to 18 years of age inclusively. Modified analyses with occlusal plane and occlusal plane perpendicular as reference planes were used to evaluate the changes of available space of the posterior mandibular arch. RESULTS: From 13 to 18 years of age, significant differences of mandibular posterior space were found among ages and sexes. The total increases of available space were 5.12 mm in the girls and 5.79 mm in the boys. For girls before age 16 and boys before age 17, the increased available space was contributed mainly by resorption of bone on the anterior border of the ramus. Mesial drift of the dental arch did not occur until the eruption of the third molars. The average available spaces increased 1.22 mm in girls less than age 16 and 1.45 mm in boys less than age 17 per side per year. CONCLUSIONS: The prediction of available space in the posterior mandibular arch should be based on age and sex.

Quantitative cervical vertebral maturation assessment in adolescents with normal occlusion: a mixed longitudinal study.

INTRODUCTION: The purpose of this study was to establish a quantitative cervical vertebral maturation (CVM) system for adolescents with normal occlusion. METHODS: Mixed longitudinal data were used. The subjects included 87 children and adolescents from 8 to 18 years old with normal occlusion (32 boys, 55 girls) selected from 901 candidates. Sequential lateral cephalograms and hand-wrist films were taken once a year for 6 years. The lateral cephalograms of all subjects were divided into 11 maturation groups according to the Fishman skeletal maturity indicators. The morphologic characteristics of the second, third, and fourth cervical vertebrae at 11 developmental stages were measured and analyzed. RESULTS: Three characteristic parameters (H4/W4, AH3/PH3, @2) were selected to determine the classification of CVM. With 3 morphologic variables, the quantitative CVM system including 4 maturational stages was established. An equation that can accurately estimate the maturation of the cervical vertebrae was established: CVM stage=-4.13+3.57xH4/W4+4.07xAH3/PH3+0.03x@2. CONCLUSIONS: The quantitative CVM method is an efficient, objective, and relatively simple approach to assess the level of skeletal maturation during adolescence.

Computational characterization and identification of human polycystic ovary syndrome genes.

Human polycystic ovary syndrome (PCOS) is a highly heritable disease regulated by genetic and environmental factors. Identifying PCOS genes is time consuming and costly in wet-lab. Developing an algorithm to predict PCOS candidates will be helpful. In this study, for the first time, we systematically analyzed properties of human PCOS genes. Compared with genes not yet known to be involved in PCOS regulation, known PCOS genes display distinguishing characteristics: (i) they tend to be located at network center; (ii) they tend to interact with each other; (iii) they tend to enrich in certain biological processes. Based on these features, we developed a machine-learning algorithm to predict new PCOS genes. 233 PCOS candidates were predicted with a posterior probability >0.9. Evidence supporting 7 of the top 10 predictions has been found.

[Longitudinal changes of posterior available spaces of lower dental arch in adolescents with normal occlusion from 13 to 18 years of age].

OBJECTIVE: To investigate the changes of available spaces of posterior arch segments in mandibular dentition from 13 to 18 years of age, which would provide information for space analysis of whole dental arch in adolescents. METHODS: Twenty-six adolescents (12 males, 14 females) with normal occlusion were selected. All of the subjects had lateral cephalograms taken at the same time each year for 6 years. Longitudinal cephalometry and statistic analysis were conducted for all subjects. RESULTS: Significant differences of available space were found between males and females. The growth of available space from 13 to 18 years of age was 5.12 mm in females and 5.79 mm in males. The completion of mandibular remodeling in males lagged behind females for about 1 year. No significant increase was found in girls beyond 16 years and in boys beyond 17 years. There was a 1.22 mm increase on each side per year in females until 16 years and a 1.45 mm increase in males until 17 years. The increase of available space was made partly by resorption of bone from the anterior border of the ramus and partly by mesial movement of the first molar. The mesial movement of dental arch was probably stimulated by the eruption of the third molars. CONCLUSIONS: The prediction of available space should be based on age and sex.

[Longitudinal changes of crown inclination in juveniles with normal occlusion].

OBJECTIVE: To investigate the longitudinal changes in crown inclination of permanent incisors and first molars in juveniles with normal occlusion. METHODS: The untreated sample comprised 20 subjects (6 males and 14 females) with normal occlusion from the Research Centre for Craniofacial Growth and Development of Peking University School and Hospital of Stomatology. Crown inclination was evaluated with Biaggini Rayset in two stages, stage I with first molars and four incisors in occlusion (mean, 9.5 +/- 0.9 years) and stage II with the second molars in occlusion (mean, 13.7 +/- 1.3 years). RESULTS: No significant difference was found between sexual groups. The crown inclination of the upper central incisors decreased (P < 0.001). The crown inclination of the lower central and lateral incisors increased (P < 0.01 and P < 0.05, respectively). The crown inclination of maxillary molars decreased with growth (P < 0.001), whereas that of mandibular molars increased with growth (P < 0.001). CONCLUSIONS: Maxillary molars tended to become upright lingually, whereas mandibular molars upright buccally with growth.