Heterodimeric BMP-2/7 Antagonizes the Inhibition of All-Trans Retinoic Acid and Promotes the Osteoblastogenesis

Objectives

Hypervitaminosis A and alcoholism can result in a low mineral density and compromised regenerative capacity of bone, thus delaying implant osteointegration. The inhibitory effect of all-trans retinoic acid on osteoblastogenesis is considered to be one of the mechanisms. We hypothesized that heterodimeric bone morphogenetic protein-2/7 could antagonize all-trans retinoic acid and enhance osteoblastogenesis, with an aim to accelerate and enhance bone regeneration and implant osteointegration.

Materials and Methods

We applied 5 ng/ml or 50 ng/ml bone morphogenetic protein-2/7 to restore the osteoblastogenesis of pre-osteoblasts (MC3T3-E1 cell line) that was inhibited by 1 µM all-trans retinoic acid. We evaluated the efficacy by assessing cell numbers (proliferation), alkaline phosphatase activity (a marker for early differentiation), osteocalcin (a marker for late differentiation), calcium deposition (a marker for final mineralization) and the expression of osteoblastogenic genes (such as Runx2, Collagen Ia, alkaline phosphatase and osteocalcin) at different time points.

Results

All-trans retinoic acid significantly inhibited the expression of all the tested osteoblastogenic genes and proteins except alkaline phosphatase activity. In the presence of ATRA, 50 ng/ml bone morphogenetic protein-2/7 not only completely restored but also significantly enhanced all the osteoblastogenic genes and proteins. On the 28^th day, mineralization was completely inhibited by all-trans retinoic acid. In contrast, 50 ng/ml BMP-2/7 could antagonize ATRA and significantly enhance the mineralization about 2.5 folds in comparison with the control treatment (no ATRA, no BMP2/7).

Conclusions

Heterodimeric bone morphogenetic protein-2/7 bears a promising application potential to significantly promote bone regeneration and implant osteointegration for the patients with hypervitaminosis A and alcoholism.     

PARP-1 Inhibitor,DPQ, Attenuates LPS-Induced Acute Lung Injury through Inhibiting NF-κB-Mediated Inflammatory Response

Acute lung injury (ALI) is characterized by overwhelming lung inflammation and anti-inflammation treatment is proposed to be a therapeutic strategy for ALI. Poly (ADP-ribose) polymerase-1 has been demonstrated to be involved in tissue inflammation and one of its inhibitors, 3, 4-Dihydro-5[4-(1-piperindinyl)butoxy]-1(2H)-isoquinoline (DPQ), exerts anti-inflammatory effect. However, it is still unclear whether the DPQ possesses the protective effect on ALI and what mechanisms are involved. In this study, we tested the effect of DPQ on the lung inflammation induced by lipopolysaccharide (LPS) challenge in mice. We found that 6 h-LPS challenge induced significant lung inflammation and vascular leakage in mice. Treatment with DPQ at the dose of 10 μg/kg markedly reduced the neutrophil infiltration, myeloperoxidase activity and up-regulation of pro-inflammatory mediators and cytokines. LPS-elevated vascular permeability was decreased by DPQ treatment, accompanied by the inhibition of apoptotic cell death in mice lungs. In addition, we isolated mice peritoneal macrophages and showed pretreatment with DPQ at 10 μM inhibited the production of cytokines in the macrophages following LPS stimulation. DPQ treatment also inhibited the phosphorylation and degradation of IκB-α, subsequently blocked the activation of nuclear factor (NF)-κB induced by LPS in vivo and in vitro. Taken together, our results show that DPQ treatment inhibits NF-κB signaling in macrophages and protects mice against ALI induced by LPS, suggesting inhibition of Poly (ADP-ribose) polymerase-1 may be a potential and effective approach to resolve inflammation for the treatment of ALI.     

Psychological Traces of China's Socio-Economic Reforms in the Ultimatum and Dictator Games

Can traces of rapid socio-economic changes within a society be reflected in experimental games? The post-Mao reforms in China provide a unique natural quasi-experiment to study people from the same society who were raised with radically different values about distribution of wealth and altruistic behavior. We tested whether the size of offers in the ultimatum and dictator games are an increasing function of the number of years Chinese citizens experienced of the Mao era (“planned economy”). For the cohort that lived throughout the entire Mao era, we found that mean offers in the two games were substantially higher than what is typically offered in laboratory studies. These offers were also higher than those of two younger Chinese cohorts. In general, the amount offered decreased with less time spent under Mao, while in the oldest group in which every member spent the same amount of time under Mao, the younger members tended to offer more, suggesting an additional effect of early education under Mao and contradicting the alternative hypothesis that generosity increases with age. These results suggest that some of the observed individual differences in the offers made in experimental games can be traced back to the values of the socio-economic era in which individuals grew up.     

Novel Mutations of ABCB6 Associated with Autosomal Dominant Dyschromatosis Universalis Hereditaria

Objective

Dyschromatosis universalis hereditaria (DUH) is a rare heterogeneous pigmentary genodermatosis, which was first described in 1933. The genetic cause has recently been discovered by the discovery of mutations in ABCB6. Here we investigated a Chinese family with typical features of autosomal dominant DUH and 3 unrelated patients with sporadic DUH.

Methods

Skin tissues were obtained from the proband, of this family and the 3 sporadic patients. Histopathological examination and immunohistochemical analysis of ABCB6 were performed. Peripheral blood DNA samples were obtained from 21 affected, 14 unaffected, 11 spouses in the family and the 3 sporadic patients. A genome-wide linkage scan for the family was carried out to localize the causative gene. Exome sequencing was performed from 3 affected and 1 unaffected in the family. Sanger sequencing of ABCB6 was further used to identify the causative gene for all samples obtained from available family members, the 3 sporadic patients and a panel of 455 ethnically-matched normal Chinese individuals.

Results

Histopathological analysis showed melanocytes in normal control’s skin tissue and the hyperpigmented area contained more melanized, mature melanosomes than those within the hypopigmented areas. Empty immature melanosomes were found in the hypopigmented melanocytes. Parametric multipoint linkage analysis produced a HLOD score of 4.68, with markers on chromosome 2q35-q37.2. A missense mutation (c.1663 C>A, p.Gln555Lys) in ABCB6 was identified in this family by exome and Sanger sequencing. The mutation perfectly cosegregated with the skin phenotype. An additional mutation (g.776 delC, c.459 delC) in ABCB6 was found in an unrelated sporadic patient. No mutation in ABCB6 was discovered in the other two sporadic patients. Neither of the two mutations was present in the 455 controls. Melanocytes showed positive immunoreactivity to ABCB6.

Conclusion

Our data add new variants to the repertoire of ABCB6 mutations with DUH.     

Associations of Green Tea and Rock Tea Consumption with Risk of Impaired Fasting Glucose and Impaired Glucose Tolerance in Chinese Men and Women

Objective

To explore the associations of green tea and rock tea consumption with risk of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT).

Methods

A multistage, stratified, cluster, random-sampling method was used to select a representative sample from Fujian Province in China. In total, 4808 subjects without cardiovascular disease, hypertension, cancer, or pancreatic, liver, kidney, or gastrointestinal diseases were enrolled in the study. A standard questionnaire was used to gather data on tea (green, rock, and black) consumption and other relevant factors. The assessment of impaired glucose regulation (IGR) was using 75-g oral glucose tolerance test (OGTT), the diagnostic criteria of normal glucose tolerance was according to American Diabetes Association.

Results

Green tea consumption was associated with a lower risk of IFG, while rock tea consumption was associated with a lower risk of IGT. The adjusted odds ratios for IFG for green tea consumption of <1, 1–15, 16–30, and >30 cups per week were 1.0 (reference), 0.42 (95% confidence intervals (CI) 0.27–0.65), 0.23 (95% CI, 0.12–0.46), and 0.41 (95% CI, 0.17–0.93), respectively. The adjusted odds ratios for IGT for rock tea consumption of <1, 1–15, 16–30, and >30 cups per week were 1.0 (reference), 0.69 (95% CI, 0.48–0.98), 0.59 (95% CI, 0.39–0.90), and 0.64 (95% CI, 0.43–0.97), respectively. A U-shaped association was observed, subjects who consumed 16–30 cups of green or rock tea per week having the lowest odds ratios for IFG or IGT.

Conclusions

Consumption of green or rock tea may protect against the development of type 2 diabetes mellitus in Chinese men and women, particularly in those who drink 16–30 cups per week.     

Draft Genome Sequence of Amphibacillus jilinensis Y1T,a Facultatively Anaerobic,Alkaliphilic and Halotolerant Bacterium

The genus Amphibacillus was established in 1990, and seven additional species were described in the past two decades. Amphibacillus jilinensis Y1^T is a facultatively anaerobic and alkaliphilic bacterium isolated from a soda lake in China. Here we describe the structural and genetic features of the draft genome about the type strain Y1^T (3,831,075 bp, with a G+C content of 37.27%). This is the first genome report of the Amphibacillus genus.     

应用改构的炭疽毒素作为靶向肿瘤细胞的药物递送系统及其效果评价

目的:通过改造炭疽毒素保护性抗原Protective Antigen (PA)及致死因子Lethal Factor (LF),尝试建立更加广谱的新型炭疽毒素靶向给药系统并对其递送效率进行定量评价.方法:采用基因工程手段,分别构建了3种改构的天然炭疽毒素保护性抗原PA及炭疽毒素的LF N端融合海肾荧光素酶(Luciferase)的LFn-linker-Luc的大肠杆菌重组表达体系.利用CCK-8法评价改构PA和LF共同作用肿瘤细胞后的细胞存活率;利用改构PA和LFn-linker-Luc与肿瘤细胞共孵育,通过测定细胞内荧光素酶活性,评价改构PA靶向肿瘤细胞的效果.结果:体外酶解实验证明构建的改构PA蛋白能够被正确地酶解成目的大小的片段;改构PA和LF共同作用肿瘤细胞能够显著降低细胞存活率;利用LFn-linker-Luc能够评价改构PA的靶向效率,PA蛋白的改构方式与其递送效率相关.结论:设计并改构的炭疽毒素药物递送系统,能够实现特异性靶向肿瘤细胞的效果,并具有更广谱的作用效果,为研制新型广谱抗肿瘤药物提供了新的思路和方法.