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Yang X.-N.,Xiamen University | Lu Y.-P.,Xiamen University | Liu J.-J.,Xiamen University | Huang J.-K.,Xiamen University | And 5 more authors.
Digestive Diseases and Sciences | Year: 2014

Background: Trefoil factor family 1 (TFF1) is a member of the TFF-domain peptide family involved in epithelial restitution and cell motility. Recently, we screened Piezo1 as a candidate TFF1-binding protein. Aim: We aimed to confirm Piezo1 as a novel TFF1 binding protein and to assess the role of this interaction in mediating gastric cancer cell mobility. Methods: This interaction was confirmed by co-immunoprecipitation and co-localisation of TFF1 and Piezo1 in GES-1 cells. We used stable RNA interference to knockdown Piezo1 protein expression and restored the expression of TFF1 in the gastric cancer cell lines SGC-7901 and BGC-823. Cell motility was evaluated using invasion assay and migration assay in vitro. The expression levels of the integrin subunits β1, β5, α1 as well as the expression of β-catenin and E-cadherin were detected by Western blot. Results: We demonstrate that TFF1, but not TFF2 or TFF3, bind to and co-localize with Piezo1 in the cytoplasm in vitro. TFF1 interacts with the C-terminal portion of the Piezo1 protein. Wound healing and trans-well assays demonstrated that the restored expression of TFF1 promoted cell mobility in gastric cancer cells, and this effect was attenuated by the knockdown of Piezo1. Western blots demonstrated the decreased expression of integrin β1 in Piezo1-knockdown cells. Conclusions: Our data demonstrate that Piezo1 is a novel TFF1 binding protein that is important for TFF1-mediated cell migration and suggest that this interaction may be a therapeutic target in the invasion and metastasis of gastric cancer. © 2014 Springer Science+Business Media. Source


Nalwoga A.,Medical Research Council Uganda Virus Research Institute MRC UVRI | Maher D.,Medical Research Council Uganda Virus Research Institute MRC UVRI | Todd J.,National Institute of Medical Research | Karabarinde A.,Medical Research Council Uganda Virus Research Institute MRC UVRI | And 2 more authors.
Tropical Medicine and International Health | Year: 2010

Objectives: To assess the nutritional status of children in a rural community with high HIV prevalence in rural Uganda and to examine the impact of HIV infection at the individual and population level. Methods: Cross-sectional population-based survey of children aged 0-12 in a cohort comprising the residents of 25 neighbouring villages in rural southwest Uganda. Anthropometric indicators of nutritional status (height for age, weight for age and weight for height) were assessed in relation to children's HIV serostatus, maternal HIV serostatus and maternal vital status. Children with a Z score of <-2 were defined as undernourished, with a Z score <-2 for weight for age defining underweight, for height for age defining stunting and for weight for height defining wasting. Results: Of 5951 children surveyed, 91% underwent anthropometric measurement: 30% were underweight, 42% stunted and 10% wasted. HIV seroprevalence among children aged 2-12 was 0.7%. The prevalence of underweight was significantly higher in HIV-positive than in HIV-negative children (52% vs. 30%), as was the prevalence of stunting (68% vs. 42%), but there was no significant difference in the prevalence of wasting (4% vs. 9%). There were no significant differences in the prevalences of indicators of undernutrition in children classified by maternal HIV and vital status. Conclusions: Chronic childhood undernutrition is common in this rural community. HIV infection had a direct effect in worsening children's nutritional status, but no indirect effect in terms of maternal HIV infection or maternal death. The population-level impact of childhood HIV infection on nutritional status is limited on account of the low HIV prevalence in children. The response to undernutrition in children in Africa requires action on many fronts: not only delivering community-wide HIV and nutritional interventions but also addressing the many interacting factors that contributed to childhood undernutrition before the HIV era and still do so now. © 2010 Blackwell Publishing Ltd. Source


Wringe A.,London School of Hygiene and Tropical Medicine | Floyd S.,London School of Hygiene and Tropical Medicine | Kazooba P.,Medical Research Council | Mushati P.,Biomedical Research and Training Institute | And 6 more authors.
Tropical Medicine and International Health | Year: 2012

Objective To compare socio-demographic patterns in access to antiretroviral therapy (ART) across four community HIV cohort studies in Africa. Methods Data on voluntary counselling and testing and ART use among HIV-infected persons were analysed from Karonga (Malawi), Kisesa (Tanzania), Masaka (Uganda) and Manicaland (Zimbabwe), where free ART provision started between 2004 and 2007. ART coverage was compared across sites by calculating the proportion on ART among those estimated to need treatment, by age, sex and educational attainment. Logistic regression was used to identify socio-demographic characteristics associated with undergoing eligibility screening at an ART clinic within 2years of being diagnosed with HIV, for three sites with information on diagnosis and screening dates. Results Among adults known to be HIV-infected from serological surveys, the proportion who knew their HIV status was 93% in Karonga, 37% in Kisesa, 46% in Masaka and 25% in Manicaland. Estimated ART coverage was highest in Masaka (68%) and lowest in Kisesa (2%). The proportion of HIV-diagnosed persons who were screened for ART eligibility within 2years of diagnosis ranged from 14% in Kisesa to 84% in Masaka, with the probability of screening uptake increasing with age at diagnosis in all sites. Conclusions Higher HIV testing rates among HIV-infected persons in the community do not necessarily correspond with higher uptake of ART, nor more equitable treatment coverage among those in need of treatment. In all sites, young adults tend to be disadvantaged in terms of accessing and initiating ART, even after accounting for their less urgent need. © 2012 Blackwell Publishing Ltd. Source


Maestad O.,Chr Michelsen Institute | Mwisongo A.,National Institute of Medical Research
Health Policy | Year: 2011

Informal payments for health services are common in many transitional and developing countries. The aim of this paper is to investigate the nature of informal payments in the health sector of Tanzania and to identify mechanisms through which informal payments may affect the quality of health care. Our focus is on the effect of informal payments on health worker behaviours, in particular the interpersonal dynamics among health workers at their workplaces. We organised eight focus groups with 58 health workers representing different cadres and levels of care in one rural and one urban district in Tanzania. We found that health workers at all levels receive informal payments in a number of different contexts. Health workers sometimes share the payments received, but only partially, and more rarely within the cadre than across cadres. Our findings indicate that health workers are involved in 'rent-seeking' activities, such as creating artificial shortages and deliberately lowering the quality of service, in order to extract extra payments from patients or to bargain for a higher share of the payments received by their colleagues. The discussions revealed that many health workers think that the distribution of informal payments is grossly unfair. The findings suggest that informal payments can impact negatively on the quality of health care through rent-seeking behaviours and through frustrations created by the unfair allocation of payments. Interestingly, the presence of corruption may also induce non-corrupt workers to reduce the quality of care. Positive impacts can occur because informal payments may induce health workers to increase their efforts, and maybe more so if there is competition among health workers about receiving the payments. Moreover, informal payments add to health workers' incomes and might thus contribute to retention of health workers within the health sector. © 2010 Elsevier Ireland Ltd. Source


Lin C.-C.,Xiamen University | Zhou J.-P.,Xiamen University | Liu Y.-P.,Xiamen University | Liu J.-J.,Xiamen University | And 5 more authors.
PLoS ONE | Year: 2012

Pokemon (POK erythroid myeloid ontogenic factor), which belongs to the POK protein family, is also called LRF, OCZF and FBI-1. As a transcriptional repressor, Pokemon assumes a critical function in cellular differentiation and oncogenesis. Our study identified an oncogenic role for Pokemon in human hepatocellular carcinoma (HCC). We successfully established human HepG2 and Huh-7 cell lines in which Pokemon was stably knocked down. We demonstrated that Pokemon silencing inhibited cell proliferation and migration. Pokemon knockdown inhibited the PI3K/Akt and c-Raf/MEK/ERK pathways and modulated the expression of various cell cycle regulators in HepG2 and Huh-7 cells. Therefore, Pokemon may also be involved in cell cycle progression in these cells. We confirmed that Pokemon silencing suppresses hepatocellular carcinoma growth in tumor xenograft mice. These results suggest that Pokemon promotes cell proliferation and migration in hepatocellular carcinoma and accelerates tumor development in an Akt- and ERK-signaling-dependent manner. © 2012 Lin et al. Source

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