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Non-syndromic tooth agenesis (or non-syndromic congenitally missing tooth) is one of the most common congenital defects in humans affecting the craniofacial function and appearance. Single nucleotide polymorphisms (SNPs) have been associated with an individual’s susceptibility to these anomalies. The aim of the present study was therefore to investigate the roles of the potentially functional SNPs of BMP2 in the occurrence of tooth agenesis. Overall, four potentially functional SNPs of BMP2 (rs15705, rs235768, rs235769 and rs3178250) were selected, and their associations with the susceptibility of tooth agenesis were evaluated in a case-control study of 335 non-syndromic tooth agenesis cases and 444 healthy controls. The SNPs rs15705 and rs3178250 were found to be associated with an individual’s risk of tooth agenesis (P = 0.046 and P = 0.039, respectively). Both SNPs showed an increased risk of mandibular incisor agenesis (rs15705, AA/AC vs. CC = 1.58, 95% CI = [1.06–2.34], P = 0.024; rs3178250, TT/TC vs. CC = 1.60, 95% CI = [1.08–2.37], P = 0.020). Bioinformatics analysis indicated that these two SNPs located at the 3’-untranslated region (3’-UTR) of BMP2 might alter the binding ability of miR-1273d and miR-4639-5p, respectively, which was confirmed by luciferase activity assays in the 293A and COS7 cell lines (P < 0.001 in 293A and P < 0.01 in COS7 for miR-1273d; and P < 0.001 in both cells for miR-4639-5p). Furthermore, BMP2 mRNA expression decreased after transfecting either miR-1273d or miR-4639-5p into these two cell lines (P < 0.01 in 293A and P < 0.001 in COS7 for miR-1273d, and P < 0.01 in both cell lines for miR-4639-5p). Taken together, our findings indicate that rs15705 and rs317250 are associated with the susceptibility of non-syndromic tooth agenesis by possibly affecting miRNAs and mRNA interaction. [ABSTRACT FROM AUTHOR]

Background and Objective: China has a high burden of cervical cancer (CC) and wide disparities in CC burden exist among different socio-economic regions. In order to reduce these disparities, China’s government launched the National Cervical Cancer Screening Program in Rural Areas (NCCSPRA) in 2009. Understanding the factors associated with underutilization of CC screening among target populations is important to improve the screening participation rate, and a high participation rate is key to achieving the goals of a screening program. However, data on the knowledge of CC among target populations in program areas is lacking in China. This study will investigate the knowledge of CC prevention and control among women in specific project counties to develop a better understanding of factors that might influence CC screening participation in order to improve the implementation of the NCCSPRA. Materials and Methods: A cross-sectional survey was conducted and face-to-face interview questionnaires were completed by 308 women who received CC screening services in 6 project counties of NCCSPRA across different socio-economic regions of China. ANOVA and Chi-square tests were used to compare the knowledge rates and scores across the different subgroups. Logistic regression was conducted to examine factors associated with knowledge level. Results: The overall CC knowledge rate of the target population was only 19.5%. Regional socio-economic level, advice from doctors, age, and educational status were strong predictors of knowledge level of CC screening. Significantly lower knowledge rates and scores were identified in older women (55–64 years old), less educated women (with primary school or illiterate), women in less developed regions and women who did not receive any advice about screening results from doctors. Conclusion: The knowledge of CC screening among women in the project counties of NCCSPRA was found to be very poor. Given the importance of knowledge in encouraging women to participate in screening is key to reducing CC burden in rural women in China, it is urgent that a targeted health promotion intervention is developed and implemented in project counties, especially targeting older women, women with less education and women in less developed regions, and focus on improving their CC knowledge and encouraging them to communicate with health care providers. The health promotion intervention targeting health care providers is also important to improve their knowledge of CC and provide best advice to women. [ABSTRACT FROM AUTHOR]

The p53 tumor suppressor protein plays a critical role in cellular stress and cancer prevention. A number of post-transcriptional regulators, termed microRNAs, are closely connected with the p53-mediated cellular networks. While the molecular interactions among p53 and microRNAs have emerged, a systems-level understanding of the regulatory mechanism and the role of microRNAs-forming feedback loops with the p53 core remains elusive. Here we have identified from literature that there exist three classes of microRNA-mediated feedback loops revolving around p53, all with the nature of positive feedback coincidentally. To explore the relationship between the cellular performance of p53 with the microRNA feedback pathways, we developed a mathematical model of the core p53-MDM2 module coupled with three microRNA-mediated positive feedback loops involving miR-192, miR-34a, and miR-29a. Simulations and bifurcation analysis in relationship to extrinsic noise reproduce the oscillatory behavior of p53 under DNA damage in single cells, and notably show that specific microRNA abrogation can disrupt the wild-type cellular phenotype when the ubiquitous cell-to-cell variability is taken into account. To assess these in silico results we conducted microRNA-perturbation experiments in MCF7 breast cancer cells. Time-lapse microscopy of cell-population behavior in response to DNA double-strand breaks, together with image classification of single-cell phenotypes across a population, confirmed that the cellular p53 oscillations are compromised after miR-192 perturbations, matching well with the model predictions. Our study via modeling in combination with quantitative experiments provides new evidence on the role of microRNA-mediated positive feedback loops in conferring robustness to the system performance of stress-induced response of p53. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the effects of intervention with a combination of nutrients in the amyloid precursor protein-presenilin (APP-PSN) C57BL/6J double transgenic mouse model of Alzheimer’s disease (AD). Methods: A total of 72 2-month-old APP-PSN mice were randomly assigned to three groups. The model group (MG) was fed regular, unsupplemented chow, while the low- and high-dose treatment groups (LG and HG, respectively) were given a combination of nutrients that included phosphatidylserine, blueberry extracts, docosahexaenoic acid, and eicosapentaenoic acid as part of their diet. An additional 24 wild-type littermates that were fed unsupplemented chow served as the negative control group (NG). After 3 and 7 months of treatment, the cognitive performance was assessed with the Morris water maze and the shuttle box escape/avoidance task, and the biochemical parameters and oxidative stress were evaluated in both the blood and brain. Results: An improvement in antioxidant capacity was observed in the treatment groups relative to the MG at 3 months, while superior behavioral test results were observed in the mice of the HG and NG groups. In the MG, pycnosis was detected in neuronal nuclei, and a loss of neurons was observed in the cerebral cortex and the hippocampus. At 7 months, the β-amyloid1–42 peptide accumulation was significantly elevated in the MG but was markedly lower in the mice fed the nutrient combination. The antioxidant capacity and behavioral test scores were also higher in these mice. Conclusions: Early intervention with a combination of nutrients should be considered as a strategy for preventing cognitive decline and other symptoms associated with AD. [ABSTRACT FROM AUTHOR]