Transforming growth factor beta receptor II interacting protein-1 (TRIP-1) was recently localized in the mineralized matrices of bone and dentin. The function of TRIP-1 in the ECM is enigmatic, as it ...is known to function as an intracellular endoplasmic reticulum protein during protein synthesis. Based on its localization pattern in bones and teeth, we posited that TRIP-1 must function as a regulatory protein with multiple functions during mineralization. In this study, we determined the
function of TRIP-1 by an implantation assay performed using recombinant TRIP-1 and TRIP-1 overexpressing and knocked down cells embedded in a 3D biomimetic scaffold. After 4 weeks, the subcutaneous tissues from TRIP-1 overexpressing cells and scaffolds containing recombinant TRIP-1 showed higher expression levels of several ECM proteins such as fibronectin and collagen I. Picrosirius red and polarized microscopy was used to identify the birefringence of the collagen fibrils in the extracellular matrix (ECM). Interestingly, knockdown of TRIP-1 resulted in lower fibronectin and downregulation of the activation of the ERK MAP kinase. We further demonstrate that TRIP-1 overexpression leads to higher expression of pro-angiogenic marker VEGF and downregulation of anti-angiogenic factors such as pigment epithelium-derived factor and thrombospondin. Field emission scanning electron microscope results demonstrated that TRIP-1 overexpressing cells released large amount of extracellular microvesicles which were localized on the fibrillar matrix in the ECM. Overall, this study demonstrates that TRIP-1 can promote secretion of extracellular vesicles, synthesis of key osteogenic ECM matrix proteins and promote angiogenesis.
Dentin phosphophoryn synthesized and processed predominantly by the odontoblasts, functions as both structural and signaling protein. Mechanistic studies revealed that DPP stimulation of DPSCs ...positively impacted the differentiation of DPSCs into functional odontoblasts. Results show that NF-κB signaling and transcriptional activation of genes involved in odontoblast differentiation were influenced by DPP signaling. Specifically, RelA/p65 subunit of NF-κB was identified as being responsible for the initiation of the differentiation cascade. Confocal imaging demonstrated the nuclear translocation of p65 with DPP stimulation. Moreover, direct binding of nuclear NF-κB p65 subunit to the promoter elements of Runx2, Osx, OCN, MMP1, MMP3, BMP4 and PTX3 were identified by ChIP analysis. Pharmacological inhibition of the NF-κB pathway using TPCA-1, a selective inhibitor of IKK-2 and JSH-23, an inhibitor that prevents nuclear translocation and DNA binding of p65 showed impairment in the differentiation process. Functional studies using Alizarin-Red staining showed robust mineral deposits with DPP stimulation and sparse deposition with defective odontoblast differentiation in the presence of inhibitors. In vivo expression of NF-κB targets such as OSX, OCN, PTX3 and p65 in odontoblasts and dental pulp cells from DSPP null mouse was lower when compared with the wild-type. Overall, the results suggest an important role for DPP-mediated NF-κB activation in the transcriptional regulation of early odontogenic markers that promote differentiation of DPSCs.
Downregulation of brain-derived neurotrophic factor (BDNF) and its cognate neurotrophin receptor, TrkB, were observed during the progression of dementia, but whether the Alzheimer's disease (AD) ...pathological lesions diffuse plaques, (DPs), neuritic plaques (NPs), and neurofibrillary tangles (NFTs) are related to this alteration remains to be clarified.
Negative binomial (NB) regressions were performed using gene expression data accrued from a single population of CA1 pyramidal neurons and regional hippocampal dissections obtained from participants in the Rush Religious Orders Study (RROS).
Downregulation of Bdnf is independently associated with increased entorhinal cortex NPs. Downregulation of TrkB is independently associated with increased entorhinal cortex NFTs and CA1 NPs during the progression of AD.
Results indicate that BDNF and TrkB dysregulation contribute to AD neuropathology, most notably hippocampal NPs and NFTs. These data suggest attenuating BDNF/TrkB signaling deficits either at the level of BDNF, TrkB, or downstream of TrkB signaling may abrogate NPs and/or NFTs.
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•Negative binomial models associate Bdnf &TrkB levels with Alzheimer neuropathology.•CA1 neuron and hippocampal Bdnf &TrkB levels are similar in Alzheimer's disease.•Hippocampal Bdnf inversely correlates with entorhinal cortex neuritic plaques.•Hippocampal TrkB inversely correlates with entorhinal cortex neurofibrillary tangles.•Hippocampal TrkB inversely correlates with hippocampal CA1 neuritic plaques.
Secretory microRNAs (miRNAs) have been used increasingly as biomarkers for cancers, autoimmune diseases and inflammatory diseases. They are reported as being freely circulated or encapsulated in ...microvesicles such as exosomes. This study was performed to elucidate the presence of miRNAs with exosomes in human gingival crevicular fluid (GCF), and the expression profile of miRNA-29 during orthodontic tooth movement. Four healthy volunteer and fifteen orthodontic patients were enrolled in the study. Secretory miRNA in GCF was collected and analyzed using a bioanalyzer, realtime PCR and Western blot analysis. The expression profile of secretory miR-29 family in GCF was analyzed during the course of canine retraction for 6 weeks. The results demonstrated the presence of miRNAs in the GCF. After series of ultracentrifugation and RT-PCR array, exosome-depleted fractions and pellets were isolated and we found that secretory miRNAs were detected in both the exosome-associated fraction and the exosome-depleted supernatant fraction; however, the concentration of miRNAs was higher in the exosome-associated fraction than in the exosome-depleted fraction suggesting a close association between the secretory miRNAs and exosomes in GCF. We also demonstrated the increased expression profiles of miR-29 family during six weeks of orthodontic tooth movement in humans. Secretory miRNAs are present in GCF and secretory miRNA-29 family expression profiles increase during the tooth movement in humans. Secretory miRNA-29 in GCF could serve as potential biomarkers for periodontal remodeling.
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•A model between particle image grayscale features and LOI was investigated.•GA-ELM has higher accuracy, ability, and stability in detecting LOI than ELM.•A new method for LOI ...detection based on image recognition was investigated.
Loss on ignition (LOI) is an essential evaluation index for fly ash triboelectric separation to recover unburned carbon products, and an important basis to regulate the technology parameters of triboelectric separation. Due to the problems of the traditional cauterization method, such as complex process, time-consuming, and error interference, the purpose of the paper is to introduce a new method for rapid detection of fly ash LOI based on image recognition and machine learning. An image recognition technique was applied to extract image grayscale features of unburned carbon particles recycled by triboelectric separation. The extreme learning machine (ELM) and genetic algorithm-optimized extreme learning machine (GA-ELM) neural networks established the relationship between grayscale feature parameters and LOI. Fly ash original samples and electrowinning experimental samples were used to evaluate the feasibility of 2 neural networks. The results showed that the evaluation indexes of GA-ELM network consisted of R2 is 95.218%, MAE is 0.0041546%, RMSE is 0.006709% and MAPE is 0.04213% at different voltages in the triboelectric separation experiments. The detection accuracy and detection ability of GA-ELM network was higher than ELM model. Therefore, the method can quickly and accurately detect the LOI of unburned carbon recovered from fly ash triboelectric separation.
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•Separation efficiency is affected by micro characteristics of particles.•Ball milling can improve the recycling efficiency of unburned carbon in fly ash.•Effects of flow velocity and ...voltage on three kinds of particles are diverse.
It is meaningful to investigate fly ash triboelectrostatic separation from a microscopic point of view. The ball milling pretreatment was proposed to improve the recycling efficiency (RC) of unburned carbon in fly ash. Particles models were established referring to the microscopic characteristics of particles obtained by scanning electron microscope (SEM). Electrostatic separation of three particles with different microscopic characteristics was analyzed by CFD-DEM coupled calculation. The comparative experiments between pretreated and untreated particles were performed. The feasibility of ball milling pretreatment was evaluated based on the loss on ignition (LOI) and productivity (PR). The results show that microscopic characteristics of particles have a serious impact on separation. Higher voltage is beneficial to the separation, but the flow velocity needs to consider the particles characteristics. It is difficult to realize high-efficiency separation by adjusting flow velocity and voltage. The ball milling treatment can destroy the complex microscopic characteristics of particles and reduce the particle size. As compared with untreated particles, the RC and PR of unburnt carbon for particles treated by ball milling can be increased by 2.19% and 32.38% respectively. The flow velocity of 10 m/s and voltage of 15 kV are suitable operating conditions.
Abstract Objective This study was designed to measure the circulating level of microparticles (MP) in patients with type 2 diabetes mellitus versus healthy volunteers and to evaluate their ...correlation with arterial elasticity and endothelium-dependent dilation. Methods Flow cytometry was used to measure the circulating levels of MP, including annexinV+MP, platelet-derived microparticles (PMP), leukocyte-derived microparticles (LMP) and endothelial microparticles (EMP), in 63 patients with type 2 diabetes mellitus and 29 healthy volunteers. Brachial ankle pulse wave velocity (baPWV) and endothelium-dependent flow-mediated dilation (FMD) of the brachial artery were also measured. Results The levels of annexinV+MP, PMP, LMP, CD31+/CD42−EMP and CD51+EMP increased significantly in diabetic patients compared with healthy controls ( P < 0.001). Correlation analysis showed that HbA1c was positively correlated to CD31+/CD42−EMP ( r s = 0.337, P = 0.008) and CD51+EMP ( r s = 0.266, P = 0.038). FMD in diabetic patients was significantly lower than that in healthy individuals ( P = 0.007). FMD was negatively correlated to CD31+/CD42−EMP ( r s = −0.441, P = 0.008) and CD51+EMP ( r s = −0.405, P = 0.016). baPWV level in diabetic patients was significantly higher than that in healthy individuals ( P < 0.001). baPWV was positively correlated to CD31+/CD42−EMP ( r s = 0.497, P < 0.001) and CD51+EMP ( r s = 0.428, P = 0.001). Multiple regression analysis indicated that EMP was an independent risk factor of FMD and baPWV. Conclusions The circulating level of microparticles increases in patients with type 2 diabetes. The level of endothelial microparticles is closely associated with vascular dysfunction.
This meta-analysis assessed the treatment effectiveness of acupuncture in patients with vascular dementia.
The PubMed, Embase, Cochrane library, and China National Knowledge Infrastructure were ...searched to identify eligible randomized controlled trials (RCTs). The odds ratios (ORs) and weighted mean differences (WMDs) with 95 % confidence intervals (CIs) were used to assess the pooled effect estimates using a random-effects model for categorical and continuous outcomes, respectively.
Thirty-four RCTs (2672 patients) were selected for the final meta-analysis. The use of acupuncture showed association with an increased incidence of effective rate (OR: 3.28; 95 % CI: 2.54–4.24; P < 0.001). The pooled WMDs revealed that acupuncture was significantly associated with an improvement in the Hasegawa dementia scale (HDS) (WMD: 4.31; 95 % CI: 3.15–5.47; P < 0.001), and Mini-Mental State Examination scores (MMSE) (WMD: 3.07; 95 % CI: 2.40–3.74; P < 0.001). However, the use of acupuncture showed no association with the level of Activities of daily living (ADL) (WMD: 1.93; 95 % CI: − 2.53 to 6.38; P = 0.397). Finally, acupuncture was associated with lower levels of Scale for the differentiation of syndromes of vascular dementia (SDSVD) (WMD: − 2.15; 95 % CI: − 4.14 to − 0.16; P = 0.034), and National Institutes of Health stroke scale (NIHSS) (WMD: − 3.90; 95 % CI: − 4.87 to − 2.94; P < 0.001).
Acupuncture is probably helpful in vascular stroke, but strong supportive data are not yet available. Acupuncture should be used cautiously, owing to the analysis of this study based on low to moderate evidence. Further high-quality, large-scale RCTs should be conducted.
•Acupuncture is probably helpful in vascular stroke.•Unfortunately, strong supportive data are not yet available.•This study revealed low/moderate evidence, and acupuncture should be used cautiously.
Previous publications indicate that Alzheimer's Disease (AD) related cortical atrophy may develop in asymmetric patterns, with accentuation of the left hemisphere. Since fluorodeoxyglucose positron ...emission tomography (FDG PET) measurements of the regional cerebral metabolic rate of glucose (rCMRgl) provide a sensitive and specific marker of neurodegenerative disease progression, we sought to investigate the longitudinal pattern of rCMRgl in amyloid-positive persons with mild cognitive impairment (MCI) and dementia, hypothesizing asymmetric declines of cerebral glucose metabolism.
Using florbetapir PET and cerebrospinal fluid (CSF) measures to define amyloid-β (Aβ) positivity, 40 Aβ negative (Aβ-) cognitively unimpaired controls (CU; 76 ± 5y), 76 Aβ positive (Aβ+) persons with MCI (76 ± 7y) and 51 Aβ + persons with probable AD dementia (75 ± 7y) from the AD Neuroimaging Initiative (ADNI) were included in this study with baseline and 2-year follow-up FDG PET scans. The degree of lateralization of longitudinal rCMRgl declines in subjects with Aβ + MCI and AD in comparison with Aβ- CU were statistically quantified via bootstrapped lateralization indices (LI); range − 1 (right) to 1 (left).
Compared to Aβ- CU, Aβ + MCI patients showed marked left hemispheric lateralization (LI: 0.78). In contrast, modest right hemispheric lateralization (LI: −0.33) of rCMRgl declines was found in Aβ + persons with probable AD dementia. Additional comparisons of Aβ + groups (i.e. MCI and probable AD dementia) consequently indicated right hemispheric lateralization (LI: −0.79) of stronger rCMRgl declines in dementia stages of AD. For all comparisons, voxel-based analyses confirmed significant (pFWE<0.05) declines of rCMRgl within AD-typical brain regions. Analyses of cognitive data yielded predominant decline of memory functions in both MCI and dementia stages of AD.
These data indicate that in early stages, AD may be characterized by a more lateralized pattern of left hemispheric rCMRgl declines. However, metabolic differences between hemispheres appear to diminish with further progression of the disease.
•Lateralized cerebral glucose metabolism declines in Alzheimer's Disease.•Early stages show strong left-hemispheric lateralization.•Advanced stages show weak right-hemispheric lateralization.
Macrophages, a key cell in the inflammatory cascade, have been associated with poor prognosis in cancers, including breast cancer. In this study, we investigated the relationship of a subset of ...macrophages—proliferating macrophages (
promacs
)—with clinico-pathologic characteristics of breast cancer, including tumor size, grade, stage, lymph node metastases, hormone receptor status, subtype, as well as early recurrence, and survival. This study included a discovery and validation set that was conducted at two institutions and laboratories (University of California, San Francisco and University of Chicago) using two independent cohorts of patients with breast cancer. Formalin-fixed, paraffin-embedded sections and/or tissue microarrays were double-stained with anti-CD68 (a macrophage marker) and anti-PCNA (a proliferation marker) antibodies. The presence of intratumoral
promacs
was significantly correlated with high grade, hormone receptor negative tumors, and a basal-like subtype. In contrast, there was no correlation between
promacs
and tumor size, stage, or the number of the involved lymph nodes. These findings were consistent between the two study cohorts. Finally,
promac
numbers were a significant predictor of recurrence and survival. In the pooled analysis, elevated
promac
levels were associated with a 77% increased risk of dying (
P
= 0.015). The presence of
promacs
in human breast cancer may serve as a prognostic indicator for poor outcomes and early recurrence and serve as a potential cellular target for novel therapeutic interventions.
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