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.
Summary
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with abnormal T cell immune responses. We hypothesized that aberrant expression of microRNAs (miRNAs) in T cells may ...contribute to the pathogenesis of SLE. First, we analysed the expression profiles of 270 human miRNAs in T cells from five SLE patients and five healthy controls and then validated those potentially aberrant‐expressed miRNAs using real‐time polymerase chain reaction (PCR). Then, the expression of mRNAs regulated by these aberrant‐expressed miRNAs was detected using real‐time PCR. Finally, miRNA transfection into Jurkat T cells was conducted for confirming further the biological functions of these miRNAs. The initial analysis indicated that seven miRNAs, including miR‐145, miR‐224, miR‐513‐5p, miR‐150, miR‐516a‐5p, miR‐483‐5p and miR‐629, were found to be potentially abnormally expressed in SLE T cells. After validation, under‐expressed miR‐145 and over‐expressed miR‐224 were noted. We further found that STAT1 mRNA targeted by miR‐145 was over‐expressed and apoptosis inhibitory protein 5 (API5) mRNA targeted by miR‐224 was under‐expressed in SLE T cells. Transfection of Jurkat cells with miR‐145 suppressed STAT1 and miR‐224 transfection suppressed API5 protein expression. Over‐expression of miR‐224 facilitates activation‐induced cell death in Jurkat cells. In the clinical setting, the increased transcript levels of STAT1 were associated significantly with lupus nephritis. In conclusion, we first demonstrated that miR‐145 and miR‐224 were expressed aberrantly in SLE T cells that modulated the protein expression of their target genes, STAT1 and API5, respectively. These miRNA aberrations accelerated T cell activation‐induced cell death by suppressing API5 expression and associated with lupus nephritis by enhancing signal transducer and activator of transcription‐1 (STAT)‐1 expression in patients with SLE.
Simultaneous enhancement of out-coupling efficiency, internal quantum efficiency, and color purity in thermally activated delayed fluorescence (TADF) emitters is highly desired for the practical ...application of these materials. We designed and synthesized two isomeric TADF emitters, 2DPyM-mDTC and 3DPyM-pDTC, based on di(pyridinyl)methanone (DPyM) cores as the new electron-accepting units and di(tert-butyl)carbazole (DTC) as the electron-donating units. 3DPyM-pDTC, which is structurally nearly planar with a very small ΔE ST, shows higher color purity, horizontal ratio, and quantum yield than 2DPyM-mDTC, which has a more flexible structure. An electroluminescence device based on 3DPyM-pDTC as the dopant emitter can reach an extremely high external quantum efficiency of 31.9% with a pure blue emission. This work also demonstrates a way to design materials with a high portion of horizontal molecular orientation to realize a highly efficient pure-blue device based on TADF emitters.
Blended learning combines online digital resources with traditional classroom activities and enables students to attain higher learning performance through well-defined interactive strategies ...involving online and traditional learning activities. Learning analytics is a conceptual framework and as a part of our Precision education used to analyze and predict students' performance and provide timely interventions based on student learning profiles. This study applied learning analytics and educational big data approaches for the early prediction of students' final academic performance in a blended Calculus course. Real data with 21 variables were collected from the proposed course, consisting of video-viewing behaviors, out-of-class practice behaviors, homework and quiz scores, and after-school tutoring. This study applied principal component regression to predict students' final academic performance. The experimental results show that students' final academic performance could be predicted when only one-third of the semester had elapsed. In addition, we identified seven critical factors that affect students' academic performance, consisting of four online factors and three traditional factors. The results showed that the blended data set combining online and traditional critical factors had the highest predictive performance.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Inflammatory markers such as interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-α) are elevated in dialysis patients and can predict cardiovascular events and all-cause mortality. Endotoxin is ...an important source and also another marker of inflammation in patients with chronic kidney disease. The aim of this study was to evaluate the impact of oral probiotics on serum levels of endotoxemia and cytokines in peritoneal dialysis (PD) patients. The decline of residual renal function, peritonitis episodes, and cardiovascular events were also recorded. From July 2011 to June 2012, a randomised, double-blind, placebo-controlled trial was conducted in PD patients. The intervention group received one capsule of probiotics containing 109 cfu Bifobacterium bifidum A218, 109 cfu Bifidobacterium catenulatum A302, 109 cfu Bifidobacterium longum A101, and 109 cfu Lactobacillus plantarum A87 daily for six months, while the placebo group received similar capsules containing maltodextrin for the same duration. Levels of serum TNF-α, interferon gamma, IL-5, IL-6, IL-10, IL-17, and endotoxin were measured before and six months after intervention. 39 patients completed the study (21 in the probiotics group and 18 in the placebo group). In patients receiving probiotics, levels of serum TNF-α, IL-5, IL-6, and endotoxin significantly decreased after six months of treatment, while levels of serum IL-10 significantly increased. In contrast, there were no significant changes in levels of serum cytokines and endotoxin in the placebo group after six months. In addition, the residual renal function was preserved in patients receiving probiotics. In conclusion, probiotics could significantly reduce the serum levels of endotoxin, pro-inflammatory cytokines (TNF-α and IL-6), IL-5, increase the serum levels of anti-inflammatory cytokine (IL-10), and preserve residual renal function in PD patients.
A 36‐year‐old woman who presented with upper limb distal weakness since the age of 15 years, with gradual progression to the lower limbs, is reported. Hereditary motor neuropathy was initially ...suspected based on distal weakness and hyporeflexia; however, whole exome sequencing accidentally revealed a compound heterozygous variant in the GNE gene, and ultrasound revealed increased homogeneous echogenicity in the involved muscles, which is characteristic of myopathic changes. Muscle magnetic resonance imaging revealed fatty infiltration in all limb muscles, sparing the triceps brachii, vastus lateralis and vastus medialis. Muscle biopsy revealed intracytoplasmic rimmed vacuole, supporting the diagnosis of GNE myopathy.
Background
Exposure to environmental endocrine‐disrupting chemicals (EDCs) is associated with allergy, chronic inflammation, and immunodeficiency. Phthalates, the common EDCs used in plastic ...industry, may act as adjuvants to disrupt immune system and enhance allergy. Plasmacytoid DCs (pDCs) are predominant cells secreting type I interferon (IFN) against infection and are professional antigen‐presenting cells in regulating adaptive immunity. However, the effects of phthalates on the function of pDCs are unknown.
Methods
Circulating pDCs were isolated from healthy subjects, were pretreated with diethylhexyl phthalate (DEHP) and butyl benzyl phthalate (BBP), and were stimulated with Toll‐like receptor (TLR)‐9 agonist CpG. IFN‐α/IFN‐β levels, surface markers, and T‐cell stimulatory function were investigated using ELISA, flow cytometry, and pDC/T‐cell coculture assay. Mechanisms were investigated using receptor antagonists, pathway inhibitors, Western blotting, and chromatin immunoprecipitation.
Results
Diethylhexyl phthalate and butyl benzyl phthalate suppressed CpG‐induced IFN‐α/IFN‐β expression in pDCs, and the effect was reversed by aryl hydrocarbon receptor (AHR) antagonist. Diethylhexyl phthalate suppressed CpG‐activated mitogen‐activated protein kinase (MAPK)‐MEK1/2‐ERK‐ELK1 and NFκB signaling pathways. Diethylhexyl phthalate suppressed CpG‐induced interferon regulatory factor (IRF)‐7 expression by suppressing histone H3K4 trimethylation at IRF7 gene promoter region through inhibiting translocation of H3K4‐specific trimethyltransferase WDR5 from cytoplasm into nucleus. Butyl benzyl phthalate or diethylhexyl phthalate‐treated pDCs suppressed IFN‐γ but enhanced IL‐13 production by CD4+ T cells.
Conclusion
Phthalates may interfere with immunity against infection and promote the deviation of Th2 response to increase allergy by acting on human pDCs via suppressing IFN‐α/IFN‐β expression and modulating the ability to stimulate T‐cell responses.
Summary Objective To study the effect of intra-articular injection of meloxicam (Mobic) on the development of osteoarthritis (OA) in rats and examine concomitant changes in nociceptive behavior and ...the expression of mitogen-activated protein kinases (MAPKs) in articular cartilage chondrocytes. Methods OA was induced in Wistar rats by right anterior cruciate ligament transection (ACLT); the left knee was not treated. The OA + meloxicam (1.0 mg) group was injected intra-articularly in the ACLT knee with 1.0 mg of meloxicam once a week for 5 consecutive weeks starting 5 weeks after ACLT. The OA + meloxicam (0.25 mg) group was treated similarly with 0.25 mg meloxicam. The sham group underwent arthrotomy only and received vehicle of 0.1 mL sterile 0.9% saline injections, whereas the naive rats in meloxicam-only groups were treated similarly with 1.0- and 0.25-mg meloxicam. Nociception was measured as secondary mechanical allodynia and hind paw weight-bearing distribution at before (pre-) and 5, 10, 15, and 20 weeks post-ACLT. Histopathology of the cartilage and synovia was examined 20 weeks after ACLT. Immunohistochemical analysis was performed to examine the effect of meloxicam on MAPKs (p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK)) expression in the articular cartilage chondrocytes. Results OA rats receiving intra-articular meloxicam treatment showed significantly less cartilage degeneration and synovitis than saline-treated controls. Nociception were improved in the OA + meloxicam groups compared with the OA group. Moreover, meloxicam attenuated p38 and JNK but enhanced ERK expression in OA-affected cartilage. Conclusions Intra-articular injection of meloxicam (1) attenuates the development of OA, (2) concomitantly reduces nociception, and (3) modulates chondrocyte metabolism, possibly through inhibition of cellular p38 and JNK, but enhances ERK expression.
Matrix metalloproteinase (MMP)-2 plays critical roles in tumor development and in the metastasis of multiple cancers, including human oral cavity squamous cell carcinoma (OCSCC). One of the upstream ...regulators of MMP-2 is FOXM1, which is overexpressed in a microarray dataset of OCSCC. It is interesting that FLJ10540 exhibits similar gene expression profiles with MMP-2 and FOXM1, raising the possibility that these molecules might participate in MMP-2-elicited cancer progression and metastasis of OCSCC. To examine this connection, we first showed that FLJ10540 was significantly overexpressed in OCSCC. A strong FLJ10540 expression was significantly correlated with an advanced tumor node metastasis stage and the cumulative 5-year survival rate. Thus, an elevated FLJ10540 expression is an indicator of poor survival. Functionally, FLJ10540 had the abilities to stimulate cell migration and invasion in oral cancer cells through increased FOXM1 and MMP-2 expressions. Conversely, the depletion of the FLJ10540 expression by small interfering RNAs suppressed the FOXM1 and MMP-2 protein expressions. The suppression of either FLJ10540 or FOXM1 could cause significant inhibition on cell migratory and invasive ability in oral cancer cells. Finally, the immunohistochemical and western blotting analyses of human aggressive OCSCC specimens showed a significant positive correlation among FLJ10540, FOXM1 and MMP-2 expressions. These findings suggest that FLJ10540 is not only an important prognostic factor but also a new therapeutic target in the FLJ10540/FOXM1/MMP-2 pathway for OCSCC treatment.
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