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Background: Spinocerebellar ataxia type 3 (SCA3) is a hereditary disease caused by abnormally expanded CAG repeats in the ATXN3 gene. The study aimed to identify potential biomarkers for assessing therapeutic efficacy by investigating the associations between expanded CAG repeat size, brain and spinal cord volume loss, and motor functions in patients with SCA3. Methods: In this prospective, cross-observational study, we analyzed 3D T1-weighted MRIs from 92 patients with SCA3 and 42 healthy controls using voxel-based morphometry and region of interest approaches. Associations between expanded CAG repeat size, brain and spinal cord volume loss, and International Cooperative Ataxia Rating Scale (ICARS) scores were investigated using partial correlation and mediation analyses. Sample sizes of potential biomarkers were calculated. Results: Compared with healthy controls, SCA3 patients had lower cerebellar volume and cervical spinal cord area. SCA3 patients evolved along a stage-independent decline that began in the cerebellum, progressed to spinal cord, brainstem, thalami, and basal ganglia, and extensive subcortex. Expanded CAG repeat size was associated with right cerebellar lobule IV volume (r = − 0.423, P < 0.001) and cervical spinal cord area (r = − 0.405, P < 0.001), and higher ICARS (r = 0.416, P < 0.001). Mediation analysis revealed an indirect effect of expanded CAG repeat size on ICARS through spinal cord. Sample sizes estimation revealed that a minimum sample size was achieved with spinal cord measures. Conclusions: Our results indicate the potential of cervical spinal cord area as a biomarker for disease progression and a minimum sample size estimation in future clinical studies of SCA3. [ABSTRACT FROM AUTHOR]

Background: As the most populous nation in the world, China has now becoming an emerging ageing society. Shanghai is the first city facing the challenge of ageing demographics. Against this background, a study that employs self-rated health (SRH) assessment system was designed to explore the health status of Shanghai elders, and learn their attitudes toward health issues; as well as to investigate the determinants of SRH among Shanghai elders. Understanding SRH is crucial for finding appropriate solutions that could effectively tackle the increasing eldercare demand.Methods: This study adopted a quantitative research strategy. Using a multistage stratified cluster sampling method, we conducted a questionnaire survey in August 2011 in Shanghai, which collected 2001 valid survey responses. SRH assessments were categorized by five levels: very good, fairly good, average, fairly poor, or poor. The respondents' functional status was evaluated using the Barthel index of activities for daily living. In the data analysis, we used chi-squared test to determine differences in socio-demographic characteristics among various groups. Along with statistics, several logistic regression models were designed to determine the associations between internal influence factors and SRH.Results: Younger age (χ2 = 27.5, p < 0.05), male sex (χ2 = 11.5, p < 0.1), and living in the suburbs (χ2 = 55.1, p < 0.05) were associated with better SRH scores. Higher SRH scores were also linked with health behaviour of the respondents; namely, do not smoke (χ2 = 18.0, p < 0.1), do not drink (χ2 = 18.6, p < 0.1), or engage in regular outdoor activities (χ2 = 69.3, p < 0.05). The respondents with better social support report higher SRH scores than those without. Respondents' ability to hear (χ2 = 38.7, p < 0.05), speak (χ2 = 16.1, p < 0.05) and see (χ2 = 78.3, p < 0.05) impacted their SRH scores as well. Meanwhile, chronic illness except asthma was a major influence factor in low SRH score. Applying multiple regression models, a series of determinants were analysed to establish the extent to which they contribute to SRH. The impact of these variables on SRH scores were 6.6% from socio-demographic and health risk behaviours, 2.4% from social support, 8.5% from mental health, 20% from physical conditions, and13% from chronic diseases.Conclusions: This is the first study that examines the determinants of SRH among Shanghai elders. Nearly 40% of our study's respondents reported their health status as "good". The main determinants of SRH among elders include living condition, health risk behaviour, social support, health status, and the economic status of the neighbourhood. [ABSTRACT FROM AUTHOR]

Background: Mitogen/extracellular signal-regulated kinase kinase-5 (MEK5) has been confirmed to play a pivotal role in tumor carcinogenesis and progression. However, few studies have investigated the role of MEK5 in colorectal cancer (CRC).Methods: MEK5 expression was determined by immunohistochemistry (IHC) in tissue microarrays (TMAs) containing 2 groups of tissues, and western blotting was used to confirm MEK5 expression in 8 cases of primary CRC tissues and paired normal mucosa. RNA interference was used to verify the biological function of MEK5 gene in the development of CRC.Results: IHC revealed the expression of MEK5 was higher in tumor tissues (38.1 %), compared with adjacent normal tissue (8.3 %). Western blot showed that, MEK5 expression was upregulated in CRC tumor tissues compared with normal tissue. Analysis of clinical pathology parameters indicated MEK5 overexpression was significantly correlated with the depth of invasion, lymph node metastasis, distant metastasis and histological grade. Survival analysis revealed that MEK5 overexpression negatively correlated with cancer-free survival (hazard ratio 1.64, P = 0.017). RNA interference-mediated knockdown of MEK5 in SW480 colon cancer cells decreased their proliferation, division, migration and invasiveness in vitro and slowed down tumors growth in mice engrafted with the cells.Conclusion: MEK5 plays an important role in CRC progression and may be a potential molecular target for the treatment of CRC. [ABSTRACT FROM AUTHOR]

Background: Spinal muscular atrophy (SMA) is an autosomal recessive hereditary disorder caused by mutations of the survival motor neuron 1 (SMN1) gene. Recently, high-resolution DNA melting analysis (HRMA) with saturation LC Green dyes has become a powerful post-PCR technique for genotyping or mutation scanning. So far, no studies have applied HRMA to the molecular analysis of SMA. Methods: The exon 7 and the flanking area of the SMN1 and SMN2 genes of 55 SMA patients and 46 unrelated normal individuals were amplified with asymmetric PCR with unlabeled probe and symmetric PCR without probe, respectively. The saturation LC Green dyes were added to the PCR system. The PCR products were loaded onto the LightScanner system and were melted from 60°C to 95°C slowly. The melting curves were acquired and analyzed by the LightScanner software. Results: Three types of melting curves that correlated with the presumed genotype of SMA patients and controls were clearly separated on the HRMA chromatogram with the unlabeled probe. The 55 SMA patients and 46 non-SMA controls were identified with HRMA with a 100% clinical sensitivity. Conclusion: The HRMA with saturation LC Green dyes and unlabeled probe appears to be a suitable, alternative method for the diagnosis of SMA, with high sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Background: Much of the debate over the evolutionary consequences of hybridization on genetic divergence and speciation results from the breakdown or reinforcement of reproductive barriers in secondary hybrid zones. Among hybrid populations established for different lengths of time following secondary contact, stronger reproductive barriers are generally expected to occur in zones with longer contact. However, in plants no detailed investigation of recent and ancient zones of secondary contact has been conducted despite the importance of such a comparative study. Here, we compare pre- and postzygotic reproductive barriers between two closely related oak species, Quercus mongolica and Q. liaotungensis, in such a situation. Results: The recorded flowering times of both species overlapped in both contact zones. The fruit set at 10 and 30 days after interspecific hand pollination was not significantly lower than that after intraspecific pollination whenever Q. mongolica or Q. liaotungensis comprised the maternal parents in both populations. These results indicated that neither prezygotic phenological barriers nor interspecific incompatibility could have resulted in the reproductive isolation between the two species in both hybrid zones. However, the proportion of hybrid seeds produced by both species in the ancient zone was significantly lower than that recorded in the recent zone of secondary contact. In addition, the proportion of hybrid seeds simulated to form, assuming both random mating and an absence of postpollination barriers, was significantly higher than that detected in the ancient contact zone but not in the recent contact zone. These results suggest stronger early-acting postzygotic isolation between the two oak species in the ancient relative to the recent contact zone. Conclusions: Our comparative study demonstrated that postzygotic barriers during seed maturity were the main contributing factor to total reproductive isolation, particularly in the ancient contact zone, which aided species delimitation. In the recently formed secondary contact zone, pre- and postzygotic barriers were not well developed, and a high frequency of natural hybridization was evident. To our knowledge this study provides the first comparison of reproductive isolation between the ancient and recent secondary contact zones in plants and helps to clarify the evolutionary consequences of hybridization in a temporal context. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) usually has a dismal prognosis because of its limited response to current pharmacotherapy and high metastatic rate. Sulfated oligosaccharide has been confirmed as having potent antitumor activities against solid tumors. Here, we explored the preclinical effects and molecular mechanisms of isomalto oligosaccharide sulfate (IMOS), another novel sulfated oligosaccharide, in HCC cell lines and a xenograft model.Methods: The effects of IMOS on HCC proliferation, apoptosis, adhesion, migration, and invasiveness in vitro were assessed by cell counting, flow cytometry, adhesion, wound healing, and transwell assays, respectively. The roles of IMOS on HCC growth and metastasis in xenograft models were evaluated by tumor volumes and fluorescent signals. Total and phosphorylated protein levels of AKT, ERK, and JNK as well as total levels of c-MET were detected by Western blotting. IMOS-regulated genes were screened by quantitative reverse-transcription PCR (qRT-PCR) array in HCCLM3-red fluorescent protein (RFP) xenograft tissues and then confirmed by qRT-PCR in HepG2 and Hep3B cells.Results: IMOS markedly inhibited cell proliferation and induced cell apoptosis of HCCLM3, HepG2, and Bel-7402 cells and also significantly suppressed cell adhesion, migration, and invasion of HCCLM3 in vitro. At doses of 60 and 90 mg/kg/d, IMOS displayed robust inhibitory effects on HCC growth and metastasis without obvious side effects in vivo. The levels of pERK, tERK, and pJNK as well as c-MET were significantly down-regulated after treatment with 16 mg/mL IMOS. No obvious changes were found in the levels of pAkt, tAkt, and tJNK. Ten differentially expressed genes were screened from HCCLM3-RFP xenograft tissues after treatment with IMOS at a dose of 90 mg/kg/d. Similar gene expression profiles were confirmed in HepG2 and Hep3B cells after treatment with 16 mg/mL IMOS.Conclusions: IMOS is a potential anti-HCC candidate through inhibition of ERK and JNK signaling independent of p53 and worth studying further in patients with HCC, especially at advanced stages. [ABSTRACT FROM AUTHOR]