Abstract Extravillus trophoblast (EVT) invasion plays a critical role in placental development. Integrins bind to extracellular matrix (ECM) proteins to mediate EVT cell adhesion, migration, and ...invasion. Changes in O -glycans on β1-integrin have been found to regulate cancer cell behavior. We hypothesize that O -glycosyltransferases can regulate EVT invasion through modulating the glycosylation and function of β1-integrin. Here, we found that the GALNT1 and GALNT2 mRNA were highly expressed in HTR8/SVneo and first trimester EVT cells. Immunohistochemstry and immunofluorescence staining showed that GALNT2 was expressed in subpopulations of EVT cells in deciduas, but not in syncytiotrophoblasts and cytotrophoblasts of placental villi. The percentage of GALNT2-positive EVT cells increased with gestational ages. Overexpression of GALNT2 in HTR8/SVneo cells significantly enhanced cell-collagen IV adhesion, but suppressed cell migration and invasion. Notably, we found that GALNT2 increased the expression of Tn antigen (GalNAc-Ser/Thr) on β1-integrin as revealed by Vicia Villosa agglutinin (VVA) binding. Furthermore, GALNT2 suppressed the phosphorylation of focal adhesion kinase (FAK), a crucial downstream signaling molecule of β1-integrin. Our findings suggest that GALNT2 is a critical initiating enzyme of O -glycosylation for regulating EVT invasion.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary
Background
Acral melanoma (AM) is the most common histopathological subtype of malignant melanoma in Asians. However, differences in the mutational profiles underlying AM and nonacral ...cutaneous melanoma (NAM) in Asians are not well understood.
Objectives
To augment the understanding of the prevalence, patterns and associations of various mutations between different subtypes of melanoma.
Methods
We performed comprehensive genomic profiling of 409 cancer‐associated genes, using next‐generation sequencing, in 66 primary melanomas comprised of 45 AMs and 21 NAMs.
Results
Most of the AMs (n = 27/45; 60%), but only five of 21 (24%) NAMs, were triple wild‐type (triple‐WT) tumours. Compared with AMs, NAMs exhibited a significantly higher frequency of BRAF mutations. The frequencies of NRAS/KRAS mutations, cell‐cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and gains of receptor tyrosine kinase genes were significantly higher in AMs. Ulceration was found at significantly higher rates in the AMs and NAMs with cell‐cycle aberrations and gains of receptor tyrosine kinase genes. Notably, cell‐cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma‐specific survival in the 66 patients with melanoma and especially in the 45 patients with AM. Multivariate analysis showed that lymph node metastasis and cell‐cycle aberrations were independent prognostic factors of melanoma‐specific survival.
Conclusions
This study strengthens our understanding of the patterns and clinical associations of oncogenic mutations in AMs and NAMs in Asians.
What's already known about this topic?
Mutation frequencies of driver genes vary between melanoma subtypes.
Acral melanoma is the most common subtype of melanoma in Asians.
KIT mutations and copy number variations occur more frequently in the acral subtype of melanoma than in the nonacral subtype
What does this study add?
NRAS/KRAS mutations, cell‐cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and amplifications of receptor tyrosine kinase genes were significantly enriched in acral melanoma and could be potential targets for treatment.
Melanomas with cell‐cycle aberrations and gains in receptor tyrosine kinase genes were significantly more likely to contain ulceration.
What is the translational message?
Cell‐cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma‐specific survival.
These observations should be explored further for future drug development.
Linked Comment: Johansson. Br J Dermatol 2020; 182:1085.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Fracture liaison services (FLS) have been demonstrated to improve outcomes following osteoporotic fracture. The aim of this systematic literature review (SLR) was to determine the characteristics of ...an FLS that lead to improved patient outcomes. We conducted a SLR, including articles published between 2000 and February 2017, using global (Medline, EMBASE, PubMed and Cochrane Library) and local databases. Studies including patients aged ≥ 50 years with osteoporotic fractures enrolled in an FLS were assessed. Information extracted from each article included key person coordinating the FLS (physician, nurse or other healthcare professional), setting (hospital vs community), intensity (single vs multiple), duration (long vs short term), fracture type and gender. A meta-analysis of randomised controlled trials was conducted based on the key person coordinating the FLS. Out of 7236 articles, 57 were considered to be high quality and identified for further analysis. The SLR identified several components which contributed to FLS success, including multidisciplinary involvement, driven by a dedicated case manager, regular assessment and follow-up, multifaceted interventions and patient education. Meta-analytic data confirm the effectiveness of an FLS following an osteoporotic fracture: approximate 27% increase in the likelihood of BMD testing and up to 21% increase in the likelihood of treatment initiation compared with usual care. The balance of evidence indicates that the multifaceted FLS and dedicated coordination are important success factors that contribute to effective FLS interventions which reduce fracture-related morbidity and mortality.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To establish an ideal microenvironment for regenerating maxillofacial defects, recent research interests have concentrated on developing scaffolds with intricate configurations and manipulating the ...stiffness of extracellular matrix toward osteogenesis. Herein, we propose to infuse a degradable RGD-functionalized alginate matrix (RAM) with osteoid-like stiffness, as an artificial extracellular matrix, to a rigid 3D-printed hydroxyapatite scaffold for maxillofacial regeneration. The 3D-printed hydroxyapatite scaffold was produced by microextrusion technology and showed good dimensional stability with consistent microporous detail. RAM was crosslinked by calcium sulfate to manipulate the stiffness, and its degradation was accelerated by partial oxidation using sodium periodate. The results revealed that viability of bone marrow stem cells was significantly improved on the RAM and was promoted on the oxidized RAM. In addition, the migration and osteogenic differentiation of bone marrow stem cells were promoted on the RAM with osteoid-like stiffness, specifically on the oxidized RAM. The in vivo evidence revealed that nonoxidized RAM with osteoid-like stiffness upregulated osteogenic genes but prevented ingrowth of newly formed bone, leading to limited regeneration. Oxidized RAM with osteoid-like stiffness facilitated collagen synthesis, angiogenesis, and osteogenesis and induced robust bone formation, thereby significantly promoting maxillofacial regeneration. Overall, this study supported that in the stabilized microenvironment, oxidized RAM with osteoid-like stiffness offered requisite mechanical cues for osteogenesis and an appropriate degradation profile to facilitate bone formation. Combining the 3D-printed hydroxyapatite scaffold and oxidized RAM with osteoid-like stiffness may be an advantageous approach for maxillofacial regeneration.
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CMK, NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Despite optimal pharmacotherapy and cognitive-behavioral treatments, a proportion of patients with obsessive-compulsive disorder (OCD) remain refractory to treatment. Neurosurgical ablative or ...nondestructive stimulation procedures to treat these refractory patients have been investigated. However, despite the potential benefits of these surgical procedures, patients show significant surgery-related complications. This preliminary study investigated the use of bilateral thermal capsulotomy for patients with treatment-refractory OCD using magnetic resonance-guided focused ultrasound (MRgFUS) as a novel, minimally invasive, non-cranium-opening surgical technique. Between February and May 2013, four patients with medically refractory OCD were treated with MRgFUS to ablate the anterior limb of the internal capsule. Patients underwent comprehensive neuropsychological evaluations and imaging at baseline, 1 week, 1 month and 6 months following treatment. Outcomes were measured with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety (HAM-A), and treatment-related adverse events were evaluated. The results showed gradual improvements in Y-BOCS scores (a mean improvement of 33%) over the 6-month follow-up period, and all patients showed almost immediate and sustained improvements in depression (a mean reduction of 61.1%) and anxiety (a mean reduction of 69.4%). No patients demonstrated any side effects (physical or neuropsychological) in relation to the procedure. In addition, there were no significant differences found in the comprehensive neuropsychological test scores between the baseline and 6-month time points. This study demonstrates that bilateral thermal capsulotomy with MRgFUS can be used without inducing side effects to treat patients with medically refractory OCD. If larger trials validate the safety, effectiveness and long-term durability of this new approach, this procedure could considerably change the clinical management of treatment-refractory OCD.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Mechanisms of the development of abnormal metabolic phenotypes among obese population are not yet clear. In this study, we aimed to screen metabolomes of both healthy and subjects with abnormal ...obesity to identify potential metabolic pathways that may regulate the different metabolic characteristics of obesity.
We recruited subjects with body mass index (BMI) over 25 from the weight-loss clinic of a central hospital in Taiwan. Metabolic healthy obesity (MHO) is defined as without having any form of hyperglycemia, hypertension and dyslipidemia, while metabolic abnormal obesity (MAO) is defined as having one or more abnormal metabolic indexes. Serum-based metabolomic profiling using both liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry of 34 MHO and MAO individuals with matching age, sex and BMI was performed. Conditional logistic regression and partial least squares discriminant analysis were applied to identify significant metabolites between the two groups. Pathway enrichment and topology analyses were conducted to evaluate the regulated pathways.
A differential metabolite panel was identified to be significantly differed in MHO and MAO groups, including L-kynurenine, glycerophosphocholine (GPC), glycerol 1-phosphate, glycolic acid, tagatose, methyl palmitate and uric acid. Moreover, several metabolic pathways were relevant in distinguishing MHO from MAO groups, including fatty acid biosynthesis, phenylalanine metabolism, propanoate metabolism, and valine, leucine and isoleucine degradation.
Different metabolomic profiles and metabolic pathways are important for distinguishing between MHO and MAO groups. We have identified and discussed the key metabolites and pathways that may prove important in the regulation of metabolic traits among the obese, which could provide useful clues to study the underlying mechanisms of the development of abnormal metabolic phenotypes.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Resveratrol, a phytochemical found in various plants and Chinese herbs, is associated with multiple tumor-suppressing activities, has been tested in clinical trials. However, the molecular mechanisms ...involved in resveratrol-mediated tumor suppressing activities are not yet completely defined. Here, we showed that treatment with resveratrol inhibited cell mobility through induction of the mesenchymal-epithelial transition (MET) in lung cancer cells. We also found that downregulation of FOXC2 (forkhead box C2) is critical for resveratrol-mediated suppression of tumor metastasis in an in vitro and in vivo models. We also identified a signal cascade, namely, resveratrol-∣miRNA-520h-∣PP2A/C-∣Akt → NF-κB → FOXC2, in which resveratrol inhibited the expression of FOXC2 through regulation of miRNA-520h-mediated signal cascade. This study identified a new miRNA-520h-related signal cascade involved in resveratrol-mediated tumor suppression activity and provide the clinical significances of miR-520h, PP2A/C and FOXC2 in lung cancer patients. Our results indicated a functional link between resveratrol-mediated miRNA-520h regulation and tumor suppressing ability, and provide a new insight into the role of resveratrol-induced molecular and epigenetic regulations in tumor suppression.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The analysis aimed to identify the treatment gaps in current fracture liaison services (FLS) and to provide recommendations for best practice establishment of future FLS across the Asia-Pacific ...region. The findings emphasize the unmet need for the implementation of new programs and provide recommendations for the refinement of existing ones. The study’s objectives were to evaluate fracture liaison service (FLS) programs in the Asia-Pacific region and provide recommendations for establishment of future FLS programs. A systematic literature review (SLR) of Medline, PubMed, EMBASE, and Cochrane Library (2000–2017 inclusive) was performed using the following keywords: osteoporosis, fractures, liaison, and service. Inclusion criteria included the following: patients ≥ 50 years with osteoporosis-related fractures; randomized controlled trials or observational studies with control groups (prospective or retrospective), pre–post, cross-sectional and economic evaluation studies. Success of direct or indirect interventions was assessed based on patients’ understanding of risk, bone mineral density assessment, calcium intake, osteoporosis treatment, re-fracture rates, adherence, and mortality, in addition to cost-effectiveness. Overall, 5663 unique citations were identified and the SLR identified 159 publications, reporting 37 studies in Asia-Pacific. These studies revealed the unmet need for public health education, adequate funding, and staff resourcing, along with greater cooperation between departments and physicians. These actions can help to overcome therapeutic inertia with sufficient follow-up to ensure adherence to recommendations and compliance with treatment. The findings also emphasize the importance of primary care physicians continuing to prescribe treatment and ensure service remains convenient. These findings highlight the limited evidence supporting FLS across the Asia-Pacific region, emphasizing the unmet need for new programs and/or refinement of existing ones to improve outcomes. With the continued increase in burden of fractures in Asia-Pacific, establishment of new FLS and assessment of existing services are warranted to determine the impact of FLS for healthcare professionals, patients, family/caregivers, and society.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This work presents the synthesis of platinum nanoparticles (Pt NPs) and their subsequent deposition on the nitrogen-doped carbon nanotubes, which have been directly grown on a carbon cloth (CNT-CC ...electrode). The CNT-CC electrode provides a fast electron-transfer path to the carbon cloth, resulting in energy-loss reduction and enhancing catalytic activity of Pt NPs. The N-dopants in CNT serve as the defect sites to enhance nucleation of Pt particles. The reduction of the Pt precursor salt was carried out in the ethylene glycol solution at an elevated temperature. In order to control the Pt NP size, the pH of the reaction solution was controlled by the addition of NaOH. Zeta potential measurements of the as-prepared sample indicate that a higher zeta potential results in a smaller particle size, due to a stronger electrostatic repulsion between NPs. This serves a powerful tool for size control of the Pt nanoparticle. The Pt NPs dispersed on the CNT-CC have an average size of 2.81 nm (Pt/CNT-CC) prepared using 15 mM NaOH, with high uniformity under electron microscopy. Cyclic voltammetry measurements of the electrocatalytic activity of the Pt/CNT-CC for methanol oxidation indicate that it exhibits excellent electrocatalytic activity and are ideal for direct methanol fuel cell applications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A general low‐cost method for ink‐jet printing transparent amorphous oxide semiconductors (see figure) is presented. The process uses metal halide precursors dissolved in acetonitrile, and this ...precursor solution is capable of forming a uniform and continuous metal halide thin film over a large area through both ink‐jet printing and blanket‐coating techniques.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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