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Introduction: The objective of the present study was to evaluate the capacity of a tissue-engineered complex of human osteoprotegerin (hOPG)-transfected periodontal ligament stem cells (PDLSCs) seeding on beta-tricalcium phosphate (β-TCP) to regenerate alveolar bone defects in New Zealand rabbits. Methods: PDLSCs were isolated from rabbit periodontal ligament tissues and expanded in vitro to enrich PDLSC numbers, and their proliferative activities and differentiation capability were evaluated under specific induction conditions. Lentiviral vector containing hOPG and enhanced green fluorescent protein (EGFP) was constructed by using Gateway technology and transfected into rabbit PDLSCs. The expression of hOPG was determined with quantitative real-time reverse transcription-polymerase chain reaction and Western blot. The PDLSCs with or without engineered hOPG were seeded on β-TCP scaffolds prior to transplantation. Morphological characterization of cells and materials was done by scanning electron microscope. Twenty rabbits with alveolar bone defects were randomly allocated into four groups and transplanted with β-TCP, PDLSCs/β-TCP, and hOPG-transfected PDLSCs/β-TCP or were left untreated as a control. Animals were sacrificed 12 weeks after operation for histological observation and histomorphometric analysis. Results: PDLSCs expressed STRO-1 and vementin and favored osteogenesis and adipogenesis in conditioned media. Expressions of hOPG were significantly upregulated after transfection of the lentiviral vector into PDLSCs. PDLSCs attached and spread well on β-TCP, and there was no significant difference in growth of PDLSCs on β-TCP between the hOPG transfection group and the non-transfection group. The histological observation and histomorphometric analysis showed that the hOPG-transfected PDLSCs/β-TCP complex exhibited an earlier mineralization and more bone formation inside the scaffold than control, β-TCP, and PDLSCs/β-TCP complexes. Implantation of hOPG-transfected PDLSCs contributed to new bone formation as determined by EGFP gene expression under circularly polarized light microscopy. Conclusions: The present study demonstrated the feasibility of β-TCP scaffolds for primary PDLSC culture and expression of hOPG gene in vitro and in vivo, and hOPG-transfected PDLSCs could serve as a potential cell source for periodontal bone regeneration, which may shed light on the potential of systemic hOPG gene therapy in combination with PDLSC tissue engineering as a good candidate in periodontal tissue engineering for alveolar bone regeneration. [ABSTRACT FROM AUTHOR]

Background Coronary atherosclerosis, the most common form of coronary artery disease (CAD), is characterized by accumulation of lipid in the walls of coronary arteries. Recent data from clinical trials have showed that high-density lipoprotein cholesterol (HDL-C) has causal role in the pathogenesis and development of coronary atherosclerosis. Cholesteryl ester transfer protein (CETP) is an important regulator of plasma HDL-C. Several genetic mutations in the CETP gene were found to be associated with HDL-C levels. The aim of the present study is to evaluate the association of HDL-C-related CETP polymorphisms and risk of coronary atherosclerosis. Methods We investigated the association of seven single nucleotide polymorphisms (SNP) (rs1800775, rs708272, rs5882, rs1532624, rs1864163, rs7499892, and rs9989419) in the CETP gene with the risk of coronary atherosclerosis and levels of HDL-C in a case-control study in China. Included in the study were 420 patients with coronary atherosclerosis and 424 healthy controls. SNP genotyping was performed by TaqMan allelic discrimination assay and serum lipid levels were measured by standard laboratory methods. Results Carriers of the AA and GA + AA genotypes of rs708272 had significant lower risks of coronary atherosclerosis (OR = 0.55, 95% CI: 0.36-0.85, p = 0.003; OR = 0.67, 95% CI: 0.50-0.90, p = 0.007, respectively) compared to those with GG genotype. These relations remained significant after adjustment for confounding effects of age, smoking, diabetes and hypertension. The rs1800775 polymorphism was significantly associated with serum levels of HDL-C in healthy controls (p = 0.04). Besides, rs708272 was in close linkage disequilibrium (LD) with rs1800775 in this study. Conclusions Our findings indicated that CETP rs708272 may be associated with the risk of coronary atherosclerosis and rs1800775 may influence serum HDL-C levels in healthy controls in Chinese. [ABSTRACT FROM AUTHOR]

Background: Suicide attempts constitute a serious clinical problem and have important implications for healthcare resources. The aim of the present study was to evaluate the effectiveness of case management using crisis postcards over a 6-month follow-up period. Method: A randomised controlled trial was conducted in Kaohsiung, Taiwan. Prevention of further suicide attempts was compared between two groups with and without the postcard intervention. The intervention group consisted of 373 participants (139 males, 234 females; age: 39.8 ± 14.0 yrs.). The control group consisted of 388 participants (113 males, 275 females; age: 40.0 ± 16.0 yrs.). A survival analysis was used to test the effectiveness of the crisis postcard intervention for the prevention of suicide reattempts. Per-protocol and intention-to-treat analyses were conducted. Results: The intention-to-treat analysis indicated that the crisis postcard had no effect (hazard ratio = 0.84; 95% CI = 0.56 - 1.29), whereas the per-protocol analysis showed a strong benefit for the crisis postcard (hazard ratio = 0.39; 95% CI = 0.21 - 0.72). Conclusion: Although the results of the present study indicated that the postcard intervention did not reduce subsequent suicide behaviour, our study provides an alteration to the postcard intervention. Further studies need to be conducted to clarify whether this type of intervention can reduce subsequent suicidal behaviour, with a particular focus on reducing the rate of loss to follow-up [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is the most common cause of end-stage kidney disease worldwide and is associated with increased morbidity and mortality in patients with both type 1 and type 2 diabetes. Recent evidence revealed that dipeptidyl peptidase-4 (DPP-4) inhibitors may exhibit a protective effect against DN. In fact, the kidney is the organ where the DPP-4 activity is the highest level per organ weight. A preclinical analysis revealed that DPP-4 inhibitors also ameliorated kidney fibrosis. In this review, we analyzed recent reports in this field and explore the renoprotective effects and possible mechanism of the DPP-4 inhibitors.

Introduction: The objective of the present study was to evaluate the capacity of a tissue-engineered complex of human osteoprotegerin (hOPG)-transfected periodontal ligament stem cells (PDLSCs) seeding on beta-tricalcium phosphate (β-TCP) to regenerate alveolar bone defects in New Zealand rabbits., Methods: PDLSCs were isolated from rabbit periodontal ligament tissues and expanded in vitro to enrich PDLSC numbers, and their proliferative activities and differentiation capability were evaluated under specific induction conditions. Lentiviral vector containing hOPG and enhanced green fluorescent protein (EGFP) was constructed by using Gateway technology and transfected into rabbit PDLSCs. The expression of hOPG was determined with quantitative real-time reverse transcription-polymerase chain reaction and Western blot. The PDLSCs with or without engineered hOPG were seeded on β-TCP scaffolds prior to transplantation. Morphological characterization of cells and materials was done by scanning electron microscope. Twenty rabbits with alveolar bone defects were randomly allocated into four groups and transplanted with β-TCP, PDLSCs/β-TCP, and hOPG-transfected PDLSCs/β-TCP or were left untreated as a control. Animals were sacrificed 12 weeks after operation for histological observation and histomorphometric analysis., Results: PDLSCs expressed STRO-1 and vementin and favored osteogenesis and adipogenesis in conditioned media. Expressions of hOPG were significantly upregulated after transfection of the lentiviral vector into PDLSCs. PDLSCs attached and spread well on β-TCP, and there was no significant difference in growth of PDLSCs on β-TCP between the hOPG transfection group and the non-transfection group. The histological observation and histomorphometric analysis showed that the hOPG-transfected PDLSCs/β-TCP complex exhibited an earlier mineralization and more bone formation inside the scaffold than control, β-TCP, and PDLSCs/β-TCP complexes. Implantation of hOPG-transfected PDLSCs contributed to new bone formation as determined by EGFP gene expression under circularly polarized light microscopy., Conclusions: The present study demonstrated the feasibility of β-TCP scaffolds for primary PDLSC culture and expression of hOPG gene in vitro and in vivo, and hOPG-transfected PDLSCs could serve as a potential cell source for periodontal bone regeneration, which may shed light on the potential of systemic hOPG gene therapy in combination with PDLSC tissue engineering as a good candidate in periodontal tissue engineering for alveolar bone regeneration.

The implications of lipid lowering drugs in the treatment of diabetic nephropathy have been considered. At the same time, the clinical efficacy of lipid lowering drugs has resulted in improvement in the cardiovascular functions of chronic kidney disease (CKD) patients with or without diabetes, but no remarkable improvement has been observed in the kidney outcome. Earlier lipid mediators have been shown to cause accumulative effects in diabetic nephropathy (DN). Here, we attempt to analyze the involvement of lipid mediators in DN. The hyperglycemia-induced overproduction of diacyglycerol (DAG) is one of the causes for the activation of protein kinase C (PKCs), which is responsible for the activation of pathways, including the production of VEGF, TGFβ1, PAI-1, NADPH oxidases, and NFҟB signaling, accelerating the development of DN. Additionally, current studies on the role of ceramide are one of the major fields of study in DN. Researchers have reported excessive ceramide formation in the pathobiological conditions of DN. There is less report on the effect of lipid lowering drugs on the reduction of PKC activation and ceramide synthesis. Regulating PKC activation and ceramide biosynthesis could be a protective measure in the therapeutic potential of DN. Lipid lowering drugs also upregulate anti-fibrotic microRNAs, which could hint at the effects of lipid lowering drugs in DN.

Background: Coronary atherosclerosis, the most common form of coronary artery disease (CAD), is characterized by accumulation of lipid in the walls of coronary arteries. Recent data from clinical trials have showed that high-density lipoprotein cholesterol (HDL-C) has causal role in the pathogenesis and development of coronary atherosclerosis. Cholesteryl ester transfer protein (CETP) is an important regulator of plasma HDL-C. Several genetic mutations in the CETP gene were found to be associated with HDL-C levels. The aim of the present study is to evaluate the association of HDL-C-related CETP polymorphisms and risk of coronary atherosclerosis., Methods: We investigated the association of seven single nucleotide polymorphisms (SNP) (rs1800775, rs708272, rs5882, rs1532624, rs1864163, rs7499892, and rs9989419) in the CETP gene with the risk of coronary atherosclerosis and levels of HDL-C in a case-control study in China. Included in the study were 420 patients with coronary atherosclerosis and 424 healthy controls. SNP genotyping was performed by TaqMan allelic discrimination assay and serum lipid levels were measured by standard laboratory methods., Results: Carriers of the AA and GA + AA genotypes of rs708272 had significant lower risks of coronary atherosclerosis (OR = 0.55, 95% CI: 0.36-0.85, p = 0.003; OR = 0.67, 95% CI: 0.50-0.90, p = 0.007, respectively) compared to those with GG genotype. These relations remained significant after adjustment for confounding effects of age, smoking, diabetes and hypertension. The rs1800775 polymorphism was significantly associated with serum levels of HDL-C in healthy controls (p = 0.04). Besides, rs708272 was in close linkage disequilibrium (LD) with rs1800775 in this study., Conclusions: Our findings indicated that CETP rs708272 may be associated with the risk of coronary atherosclerosis and rs1800775 may influence serum HDL-C levels in healthy controls in Chinese.

Background: Suicide attempts constitute a serious clinical problem and have important implications for healthcare resources. The aim of the present study was to evaluate the effectiveness of case management using crisis postcards over a 6-month follow-up period., Method: A randomised controlled trial was conducted in Kaohsiung, Taiwan. Prevention of further suicide attempts was compared between two groups with and without the postcard intervention. The intervention group consisted of 373 participants (139 males, 234 females; age: 39.8 ± 14.0 yrs.). The control group consisted of 388 participants (113 males, 275 females; age: 40.0 ± 16.0 yrs.). A survival analysis was used to test the effectiveness of the crisis postcard intervention for the prevention of suicide reattempts. Per-protocol and intention-to-treat analyses were conducted., Results: The intention-to-treat analysis indicated that the crisis postcard had no effect (hazard ratio = 0.84; 95% CI = 0.56 - 1.29), whereas the per-protocol analysis showed a strong benefit for the crisis postcard (hazard ratio = 0.39; 95% CI = 0.21 - 0.72)., Conclusion: Although the results of the present study indicated that the postcard intervention did not reduce subsequent suicide behaviour, our study provides an alteration to the postcard intervention. Further studies need to be conducted to clarify whether this type of intervention can reduce subsequent suicidal behaviour, with a particular focus on reducing the rate of loss to follow-up.