87 research outputs found

    Exogenous Expression of Human apoA-I Enhances Cardiac Differentiation of Pluripotent Stem Cells

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    The cardioprotective effects of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA-I) are well documented, but their effects in the direction of the cardiac differentiation of embryonic stem cells are unknown. We evaluated the effects of exogenous apoA-I expression on cardiac differentiation of ESCs and maturation of ESC-derived cardiomyocytes. We stably over-expressed full-length human apoA-I cDNA with lentivirus (LV)-mediated gene transfer in undifferentiated mouse ESCs and human induced pluripotent stem cells. Upon cardiac differentiation, we observed a significantly higher percentage of beating embryoid bodies, an increased number of cardiomyocytes as determined by flow cytometry, and expression of cardiac markers including ι-myosin heavy chain, β-myosin heavy chain and myosin light chain 2 ventricular transcripts in LV-apoA-I transduced ESCs compared with control (LV-GFP). In the presence of noggin, a BMP4 antagonist, activation of BMP4-SMAD signaling cascade in apoA-I transduced ESCs completely abolished the apoA-I stimulated cardiac differentiation. Furthermore, co-application of recombinant apoA-I and BMP4 synergistically increased the percentage of beating EBs derived from untransduced D3 ESCs. These together suggests that that pro-cardiogenic apoA-I is mediated via the BMP4-SMAD signaling pathway. Functionally, cardiomyocytes derived from the apoA-I-transduced cells exhibited improved calcium handling properties in both non-caffeine and caffeine-induced calcium transient, suggesting that apoA-I plays a role in enhancing cardiac maturation. This increased cardiac differentiation and maturation has also been observed in human iPSCs, providing further evidence of the beneficial effects of apoA-I in promoting cardiac differentiation. In Conclusion, we present novel experimental evidence that apoA-I enhances cardiac differentiation of ESCs and iPSCs and promotes maturation of the calcium handling property of ESC-derived cardiomyocytes via the BMP4/SMAD signaling pathway

    Promotion of knowledge and awareness of parents in HK about infant oral health care

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    Aim: To promote the knowledge and awareness of infant oral health (OH) care among Hong Kong parents with children aged 0 to 2 years through an interactive workshop and to evaluate its effectiveness. Methods: Parents were recruited from government-registered childcare centers and private playgroups. Interactive workshops consisted of a 30-minute PowerPoint presentation and 20 minutes of small-group activities, which included infant oral hygiene instruction with custom-made infant dentition models, diet analysis and question-and-answer session. Self-completed questionnaires used to evaluate the knowledge and attitude of parents were distributed before and after the workshops. Scores on general OH knowledge (range=0-18), infant OH knowledge (0-10) and parent’s attitude (0-4) were computed. Scores of at least 70% were considered proficient. Results: Among the 111 participants (aged 26 to 54 years, 64% mothers), 96% had a child aged 0 to 30 months. 30% had their children’s mouth cleaned at least twice a day. Only one participant had brought his/her child to see a dentist. Weaker aspects in parents’ OH knowledge and common misconceptions were identified in the pre-survey. Only 35% identified frequent meals as an increased caries risk; only 59% and 79% identified starchy food and formula milk as cariogenic food respectively. 58% did not know water fluoridation can prevent caries, while 33% of parents pointed out calcium supplement can prevent caries. Before the workshop, 41% had proficient general OH knowledge (mean=11.9) and 16% had proficient infant OH knowledge (mean=4.8). Over half of parents showed positive attitude (mean=3.4). Significant improvements in general OH knowledge (mean=15.6, p<0.001), infant OH knowledge (mean=8.8, p<0.001) and attitude (mean=3.9, p<0.001) were observed. Parents reflected the workshops were useful (94%) and they learned new practices to improve their infants’ OH (95%). Conclusion: Several deficiencies in oral health knowledge and behaviour are identified. The interactive workshops can effectively promote the knowledge and awareness of infant oral health care among parents with children aged 0 to 2 years. Large-scale infant oral health survey is needed. Interactive workshops with longer follow-up periods are recommended. More guidelines can be provided to parents and general dentists for prevention of caries.published_or_final_versio

    Effectiveness of a denture hygiene intervention programme among institutionalized elders

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    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

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    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

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

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    Š 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

    Efficacy, safety and immunogenicity of a human rotavirus vaccine (RIX4414) in Hong Kong children up to three years of age: A randomized, controlled trial

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    AbstractBackgroundA phase III, double-blind, randomized, controlled trial was conducted in Hong Kong to evaluate the efficacy, safety and immunogenicity of a human rotavirus vaccine, RIX4414 (Rotarix™) against severe rotavirus gastroenteritis in children up to three years of age.MethodsHealthy infants aged 6–12 weeks were enrolled between 08-December-2003 and 31-August-2005 and received two oral doses of either RIX4414 vaccine (N=1513) or placebo (N=1512) given 2 months apart. Vaccine efficacy was assessed from two weeks post-Dose 2 until the children were two and three years of age. Anti-rotavirus IgA seroconversion rate was calculated pre-vaccination and 1–2 months post-Dose 2 using ELISA (cut-off=20U/mL) for 100 infants. Safety was assessed until the children were two years of age; serious adverse events (SAEs) were recorded throughout the study period.ResultsIn children aged two and three years of life, vaccine efficacy against severe rotavirus gastroenteritis was 95.6% (95% CI: 73.1%–99.9%) and 96.1% (95% CI: 76.5%–99.9%), respectively. The seroconversion rate 1–2 months after the second dose of RIX4414 was 97.5% (95% CI: 86.8%–99.9%). At least one SAE was recorded in 439 and 477 infants who were administered RIX4414 and placebo, respectively (p-value=0.130). Six intussusception cases were reported (RIX4414=4; placebo=2) and none was assessed to be vaccine-related.ConclusionRIX4414 was efficacious, immunogenic and safe in the prevention of rotavirus gastroenteritis for at least two years post-vaccination in Hong Kong children

    Chronic intermittent hypoxia induces local inflammation of the rat carotid body via functional upregulation of proinflammatory cytokine pathways

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    Maladaptive changes in the carotid body (CB) induced by chronic intermittent hypoxia (IH) account for the pathogenesis of cardiovascular morbidity in patients with sleep-disordered breathing. We postulated that the proinflammatory cytokines, namely interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-ι, and cytokine receptors (IL-1r1, gp130 and TNFr1) locally expressed in the rat CB play a pathophysiological role in IH-induced CB inflammation. Results showed increased levels of oxidative stress (serum 8-isoprostane and nitrotyrosine in the CB) in rats with 7-day IH treatment resembling recurrent apneic conditions when compared with the normoxic control. Local inflammation shown by the amount of ED1-containing cells (macrophage infiltration) and the gene transcripts of NADPH oxidase subunits (gp91phox and p22phox) and chemokines (MCP-1, CCR2, MIP-1ι, MIP-1β and ICAM-1) in the CB were significantly more in the hypoxic group than in the control. In addition, the cytokines and receptors were expressed in the lobules of chemosensitive glomus cells containing tyrosine hydroxylase and the levels of expressions were significantly increased in the hypoxic group. Exogenous cytokines elevated the intracellular calcium ([Ca2+]i) response to acute hypoxia in the dissociated glomus cells. The effect of cytokines on the [Ca2+]i response was significantly greater in the hypoxic than in the normoxic group. Moreover, daily treatment of IH rats with anti-inflammatory drugs (dexamethasone or ibuprofen) attenuated the levels of oxidative stress, gp91phox expression and macrophage infiltration in the CB. Collectively, these results suggest that the upregulated expression of proinflammatory cytokine pathways could mediate the local inflammation and functional alteration of the CB under chronic IH conditions

    Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians

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    Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases

    Genome-Wide Association Study in Asian Populations Identifies Variants in ETS1 and WDFY4 Associated with Systemic Lupus Erythematosus

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    Systemic lupus erythematosus is a complex and potentially fatal autoimmune disease, characterized by autoantibody production and multi-organ damage. By a genome-wide association study (320 patients and 1,500 controls) and subsequent replication altogether involving a total of 3,300 Asian SLE patients from Hong Kong, Mainland China, and Thailand, as well as 4,200 ethnically and geographically matched controls, genetic variants in ETS1 and WDFY4 were found to be associated with SLE (ETS1: rs1128334, P = 2.33×10−11, OR = 1.29; WDFY4: rs7097397, P = 8.15×10−12, OR = 1.30). ETS1 encodes for a transcription factor known to be involved in a wide range of immune functions, including Th17 cell development and terminal differentiation of B lymphocytes. SNP rs1128334 is located in the 3′-UTR of ETS1, and allelic expression analysis from peripheral blood mononuclear cells showed significantly lower expression level from the risk allele. WDFY4 is a conserved protein with unknown function, but is predominantly expressed in primary and secondary immune tissues, and rs7097397 in WDFY4 changes an arginine residue to glutamine (R1816Q) in this protein. Our study also confirmed association of the HLA locus, STAT4, TNFSF4, BLK, BANK1, IRF5, and TNFAIP3 with SLE in Asians. These new genetic findings may help us to gain a better understanding of the disease and the functions of the genes involved
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