Hepatocyte growth factor enhances proteolysis and invasiveness of human nasopharyngeal cancer cells through activation of PI3K and JNK

AbstractThe hepatocyte growth factor (HGF) receptor, Met, is frequently overexpressed in nasopharyngeal cancer (NPC). Here, we showed for the first time that human NPC cells with high Met expression were more sensitive to the cell motility and invasion effect of HGF. The downregulation of Met by small interfering RNA decreased tumor cell invasion/migration. HGF significantly increased matrix metalloproteinase-9 production. This was inhibited by blocking phosphatidylinositide 3-kinase (PI3K) and c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase signaling pathways. We also demonstrated that PI3K induced activation of JNK, with Akt as a potential point of this cross-talk. These results provide new insights into the molecular mechanism responsible for NPC progression and metastasis

Effectiveness of a denture hygiene intervention programme among institutionalized elders

Objectives: To evaluate the effectiveness of a denture hygiene intervention programme in terms of improving denture cleanliness and denture stomatitis. Methods: Residents at seven elderly care homes were invited to participate in a denture hygiene programme. Clinical assessment of denture stomatitis was undertaken and denture cleanliness assessed: (i) qualitatively by the Denture Cleanliness Index ratings and (ii) quantitatively by planimetric assessments of plaque coverage from digital images using Adobe Photoshop®. Individual denture hygiene instruction was provided and denture cleanser (Polident®) supplied. Six weeks later assessments of denture stomatitis and denture cleanliness were undertaken. Results: Fifty-six participants were recruited; most had evidence of denture stomatitis (82.1%, 46) and 62.5% (35) of dentures were classified as ‘very poorly cleaned’. The mean percentage of plaque coverage was 28.11 (SD 19.64) and 37.5% (21) had evidence of plaque covering more than a third of the denture surface. Denture cleanliness was associated with denture stomatitis (P0.05).Conclusion: A 6-week denture hygiene intervention programme was effective at improving denture stomatitis and denture cleanliness among residents of elderly care homes. However, persistence of problems in denture cleanliness and denture stomatitis existed and this warrants further consideration.published_or_final_versio

Effectiveness of a denture hygiene intervention programme among institutionalized elders

Objectives: To evaluate the effectiveness of a denture hygiene intervention programme in terms of improving denture cleanliness and denture stomatitis. Methods: Residents at seven elderly care homes were invited to participate in a denture hygiene programme. Clinical assessment of denture stomatitis was undertaken and denture cleanliness assessed: (i) qualitatively by the Denture Cleanliness Index ratings and (ii) quantitatively by planimetric assessments of plaque coverage from digital images using Adobe Photoshop®. Individual denture hygiene instruction was provided and denture cleanser (Polident®) supplied. Six weeks later assessments of denture stomatitis and denture cleanliness were undertaken. Results: Fifty-six participants were recruited; most had evidence of denture stomatitis (82.1%, 46) and 62.5% (35) of dentures were classified as ‘very poorly cleaned’. The mean percentage of plaque coverage was 28.11 (SD 19.64) and 37.5% (21) had evidence of plaque covering more than a third of the denture surface. Denture cleanliness was associated with denture stomatitis (P0.05).Conclusion: A 6-week denture hygiene intervention programme was effective at improving denture stomatitis and denture cleanliness among residents of elderly care homes. However, persistence of problems in denture cleanliness and denture stomatitis existed and this warrants further consideration.published_or_final_versio

Hepatocellular carcinoma surveillance after HBsAg seroclearance

Hepatitis B surface antigen (HBsAg) seroclearance is considered the functional cure and the optimal treatment endpoint for chronic hepatitis B (CHB). Patients with CHB who cleared HBsAg generally have a favorable clinical course with minimal risk of developing hepatocellular carcinoma (HCC) or cirrhotic complications. Nevertheless, a minority of patients still develop HCC despite HBsAg seroclearance. While patients with liver cirrhosis are still recommended for HCC surveillance, whether other non-cirrhotic patients who achieved HBsAg seroclearance should remain on HCC surveillance remains unclear. This review provides an overview of the incidence of HBsAg seroclearance, the factors associated with the occurrence of HBsAg seroclearance, the durability of HBsAg seroclearance, the risk of developing HCC after HBsAg seroclearance, the risk factors associated with HCC development after HBsAg seroclearance, the role of HCC risk scores, and the implications on HCC surveillance. Existing HCC risk scores have a reasonably good performance in patients after HBsAg seroclearance. In the era of artificial intelligence, future HCC risk prediction models based on artificial intelligence and longitudinal clinical data may further improve the prediction accuracy to establish a foundation of a risk score-based HCC surveillance strategy. As different novel hepatitis B virus (HBV) antiviral agents aiming at HBsAg seroclearance are under active development, new knowledge is anticipated on the natural history and HCC risk prediction of patients treated with new HBV drugs

MicroRNA profiling study reveals MIR-150 in association with metastasis in nasopharyngeal carcinoma

© 2017 The Author(s). MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in pathogenesis of human cancers. Several miRNAs have been shown to involve in nasopharyngeal carcinoma (NPC) pathogenesis through alteration of gene networks. A global view of the miRNA expression profile of clinical specimens would be the best way to screen out the possible miRNA candidates that may be involved in disease pathogenesis. In this study, we investigated the expression profiles of miRNA in formalin-fixed paraffin-embedded tissues from patients with undifferentiated NPC versus non-NPC controls using a miRNA real-time PCR platform, which covered a total of 95 cancer-related miRNAs. Hierarchical cluster analysis revealed that NPC and non-NPC controls were clearly segregated. Promisingly, 10 miRNA candidates were differentially expressed. Among them, 9 miRNAs were significantly up-regulated of which miR-205 and miR-196a showed the most up-regulated in NPC with the highest incidence percentage of 94.1% and 88.2%, respectively, while the unique down-regulated miR-150 was further validated in patient sera. Finally, the in vitro gain-of-function and loss-of-function assays revealed that miR-150 can modulate the epithelial-mesenchymal-transition property in NPC/HK-1 cells and led to the cell motility and invasion. miR-150 may be a potential biomarker for NPC and plays a critical role in NPC tumourigenesis.Link_to_subscribed_fulltex

Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study

Background The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline. Methods and findings We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54–105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2–16 assessment waves (median = 3) and a follow-up duration of 2–15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0.023 SD/decade, 95% CI [0.011, 0.035], p < 0.001), and every additional year of education was associated with a rate of decline slightly slower for the MMSE (0.004 SD/decade less, 95% CI [0.002, 0.006], p = 0.001), but slightly faster for language (-0.007 SD/decade more, 95% CI [-0.011, -0.003], p = 0.001). APOE*4 carriers declined slightly more rapidly than non-carriers on most cognitive measures, with processing speed showing the greatest difference (-0.08 SD/decade, 95% CI [-0.15, -0.01], p = 0.019). The same overall pattern of results was found when analyses were repeated with baseline dementia cases excluded. We used only one test to represent cognitive domains, and though a prototypical one, we nevertheless urge caution in generalizing the results to domains rather than viewing them as test-specific associations. This study lacked cohorts from Africa, India, and mainland China. Conclusions Cognitive performance declined with age, and more rapidly with increasing age, across samples from diverse ethnocultural groups and geographical regions. Associations varied across cohorts, suggesting that different rates of cognitive decline might contribute to the global variation in dementia prevalence. However, the many similarities and consistent associations with education and APOE genotype indicate a need to explore how international differences in associations with other risk factors such as genetics, cardiovascular health, and lifestyle are involved. Future studies should attempt to use multiple tests for each cognitive domain and feature populations from ethnocultural groups and geographical regions for which we lacked data

COSMIC (Cohort Studies of Memory in an International Consortium): An international consortium to identify risk and protective factors and biomarkers of cognitive ageing and dementia in diverse ethnic and sociocultural groups

BACKGROUND: A large number of longitudinal studies of population-based ageing cohorts are in progress internationally, but the insights from these studies into the risk and protective factors for cognitive ageing and conditions like mild cognitive impairment and dementia have been inconsistent. Some of the problems confounding this research can be reduced by harmonising and pooling data across studies. COSMIC (Cohort Studies of Memory in an International Consortium) aims to harmonise data from international cohort studies of cognitive ageing, in order to better understand the determinants of cognitive ageing and neurocognitive disorders. METHODS/DESIGN: Longitudinal studies of cognitive ageing and dementia with at least 500 individuals aged 60 years or over are eligible and invited to be members of COSMIC. There are currently 17 member studies, from regions that include Asia, Australia, Europe, and North America. A Research Steering Committee has been established, two meetings of study leaders held, and a website developed. The initial attempts at harmonising key variables like neuropsychological test scores are in progress. DISCUSSION: The challenges of international consortia like COSMIC include efficient communication among members, extended use of resources, and data harmonisation. Successful harmonisation will facilitate projects investigating rates of cognitive decline, risk and protective factors for mild cognitive impairment, and biomarkers of mild cognitive impairment and dementia. Extended implications of COSMIC could include standardised ways of collecting and reporting data, and a rich cognitive ageing database being made available to other researchers. COSMIC could potentially transform our understanding of the epidemiology of cognitive ageing, and have a world-wide impact on promoting successful ageing

Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study

Background The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline. Methods and findings We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54–105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2–16 assessment waves (median = 3) and a follow-up duration of 2–15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0.023 SD/decade, 95% CI [0.011, 0.035], p < 0.001), and every additional year of education was associated with a rate of decline slightly slower for the MMSE (0.004 SD/decade less, 95% CI [0.002, 0.006], p = 0.001), but slightly faster for language (-0.007 SD/decade more, 95% CI [-0.011, -0.003], p = 0.001). APOE*4 carriers declined slightly more rapidly than non-carriers on most cognitive measures, with processing speed showing the greatest difference (-0.08 SD/decade, 95% CI [-0.15, -0.01], p = 0.019). The same overall pattern of results was found when analyses were repeated with baseline dementia cases excluded. We used only one test to represent cognitive domains, and though a prototypical one, we nevertheless urge caution in generalizing the results to domains rather than viewing them as test-specific associations. This study lacked cohorts from Africa, India, and mainland China. Conclusions Cognitive performance declined with age, and more rapidly with increasing age, across samples from diverse ethnocultural groups and geographical regions. Associations varied across cohorts, suggesting that different rates of cognitive decline might contribute to the global variation in dementia prevalence. However, the many similarities and consistent associations with education and APOE genotype indicate a need to explore how international differences in associations with other risk factors such as genetics, cardiovascular health, and lifestyle are involved. Future studies should attempt to use multiple tests for each cognitive domain and feature populations from ethnocultural groups and geographical regions for which we lacked data

COSMIC (Cohort Studies of Memory in an International Consortium): An international consortium to identify risk and protective factors and biomarkers of cognitive ageing and dementia...

Background: A large number of longitudinal studies of population-based ageing cohorts are in progress internationally, but the insights from these studies into the risk and protective factors for cognitive ageing and conditions like mild cognitive impairment and dementia have been inconsistent. Some of the problems confounding this research can be reduced by harmonising and pooling data across studies. COSMIC (Cohort Studies of Memory in an International Consortium) aims to harmonise data from international cohort studies of cognitive ageing, in order to better understand the determinants of cognitive ageing and neurocognitive disorders. Methods/Design: Longitudinal studies of cognitive ageing and dementia with at least 500 individuals aged 60 years or over are eligible and invited to be members of COSMIC. There are currently 17 member studies, from regions that include Asia, Australia, Europe, and North America. A Research Steering Committee has been established, two meetings of study leaders held, and a website developed. The initial attempts at harmonising key variables like neuropsychological test scores are in progress. Discussion: The challenges of international consortia like COSMIC include efficient communication among members, extended use of resources, and data harmonisation. Successful harmonisation will facilitate projects investigating rates of cognitive decline, risk and protective factors for mild cognitive impairment, and biomarkers of mild cognitive impairment and dementia. Extended implications of COSMIC could include standardised ways of collecting and reporting data, and a rich cognitive ageing database being made available to other researchers. COSMIC could potentially transform our understanding of the epidemiology of cognitive ageing, and have a world-wide impact on promoting successful ageing

Application of genetic analyses in studies of syndromic and non-syndromic cleft lip and palate

Linkage analysis is one of the first and essential steps in the localization of human disease genes. In this study, the method was first applied in mapping of the disease in two families with isolated hyperparathyroidism (FIHP) to the hyperparathyroidism-jaw tumor (HPT-JT) syndrome locus at 1q21-q32. The results suggest that a sunset of FlHP families are a variant of HPT-JT. Loss of heterozygosity at 1q21-q32 was found in tumors from a FIHP and a HPT-JT family, implying that the gene involved is a tumor suppressor gene (Paper I). Genetic analyses were applied to the studies of syndromic and non-syndromic cleft lip and palate. Van der Woude syndrome (VWS), the most common form of syndromic cleft, has been mapped to 1q32-q41. Two Swedish and three Finnish families were mapped to 1q32-q41 and the critical region was tentatively refined to 130-kb by observing recombination and shared haplotypes in the families. Microdeletion of the VWS region was unlikely. Two Finnish families were unlinked to the VWS region in 1q thus providing the first evidence of genetic heterogeneity in VWS. All families were tested for the possible modifying effect on the cleft palate phenotype from a locus in 17p11.2-p11.1. Linkage was clearly excluded, meaning that the 17p locus is not a major modifying gene (Papers II, III). A Swedish boy and his mother who both have cleft lip and palate were examined for additional clinical featured. The presence of lip pits and a distinct toe malformation led to the diagnosis of popliteal pterygium syndrome (PPS). Our analysis showed that microdeletion of the 1q VWS region was unlikely but linkage to the region could not be excluded (Paper IV). Non-syndromic cleft lip with or without cleft palate (CLP) has been tentatively mapped to candidate loci in chromosome 4, chromosomes 2, 6 and 19 with heterogeneity. Linkage to these regions as well as the 1q VWS locus was tested in 19 Swedish multi-generation CLP families. Our results showed that the group of families was unlinked to any of these regions and heterogeneity was not evidenced. This might imply a new locus or loci in the Swedish CLP families, although linkage to individual loci could be hidden by insignificant heterogeneity in the family group. Results from the non-parametric linkage analysis were insignificant. Although linkage could not be confirmed with the limited sizes of these families, data from individual families will form the basis for future studies of candidate genes derived from these loci (Paper V). In summary, genetic linkage analyses have been applied to elucidate the genetic basis of syndromic and non-syndromic cleft lip and palate, generating important clinical and genetic data. These results will be incorporated into the ongoing gene mapping efforts of these diseases. Identification of the genes involved in cleft lip and palate is essential for the diagnosis, prediction and in the future treatment of these congenital malformations