To evaluate internal tandem duplication (ITD) insertion sites and length as well as their clinical impact in younger adult patients with FLT3-ITD-positive acute myeloid leukemia (AML), sequencing after DNA-based amplification was performed in diagnostic samples from 241 FLT3-ITDmutated patients. All patients were treated on 3 German-Austrian AML Study Group protocols. Thirty-four of the 241 patients had more than 1 ITD, leading to a total of 282 ITDs; the median ITD length was 48 nucleotides (range, 15-180 nucleotides). ITD integration sites were categorized according to functional regions of the FLT3 receptor: juxtamembrane domain (JMD), n ‫؍‬ 148; JMD hinge region, n ‫؍‬ 48; beta1-sheet of the tyrosine kinase domain-1 (TKD1), n ‫؍‬ 73; remaining TKD1 region, n ‫؍‬ 13. ITD length was strongly correlated with functional regions (P < .001). In multivariable analyses, ITD integration site in the beta1-sheet was identified as an unfavorable prognostic factor for achievement of a complete remission (odds ratio, 0.22; P ‫؍‬ .01), relapsefree survival (hazard ratio, 1.86; P < .001), and overall survival (hazard ratio, 1.59; P ‫؍‬ .008). ITD insertion site in the beta1-sheet appears to be an important unfavorable prognostic factor in young adult patients with FLT3-ITD-positive AML.

• More than 90% of the patients with inv (16)

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In this study, we investigated the possibility of using local administration of allogeneic bone marrow mesenchymal stem cells (BMMSCs) to induce tissue regeneration in periodontal defects in a rat model of periodontitis. BMMSCs isolated from rats were mixed with 0.9% NaCl solution and injected into periodontal defects. Control groups were 0.9% NaCl solution or left untreated. The clinical assessments, x-rays, and histological examinations were used to evaluate the effect. At 12 wks post-transplantation, quantitative analysis revealed average probing bone loss values of 1.2 ± 0.19, 1.6 ± 0.2, and 1.7 ± 0.14; the bone regeneration rate was 53%, 45%, and 44% in the BMMSC+NaCl group, NaCl group, and untreated group, respectively. The clinical assessments, x-rays, and histological examinations revealed significant periodontal tissue regeneration in the BMMSC injection group, compared with the control groups. The ELISA results showed that TNFα, IFNγ, and IL1β were 2,674.88 ± 102.77 pg/mL vs. 3,422.1 ± 51.98 pg/mL, 609.85 ± 25.5 pg/mL vs. 803.79 ± 33.85 pg/mL, and 1,038.46 ± 76.29 pg/mL vs. 1,175.26 ± 105.55 pg/mL in the BMMSC+NaCl group and NaCl group, respectively, indicating that BMMSC injection inhibited the inflammatory factors TNFα, IFNγ, and IL1β. Our results indicate that local administration of BMMSCs can repair defects due to periodontitis, exerting anti-inflammatory and immunomodulatory functions.

No abstract

BackgroundRepetitive transcranial magnetic stimulation (rTMS) can modulate cortical excitability, and may be beneficial for motor recovery after stroke. However, the neuroplasticity effects of rTMS have not been thoroughly investigated in the early stage after stroke.ObjectiveTo comprehensively assess the effects of high- and low-frequency repetitive transcranial magnetic stimulations on motor recovery in early stroke patients, using a randomized controlled trial based on clinical, neurophysiological and functional imaging assessments.MethodsSixty hospitalized, first-ever ischemic stroke patients (within 2 weeks after stroke) with motor deficits were randomly allocated to receive, in addition to standard physical therapy, five consecutive sessions of either: (1) High-frequency (HF) rTMS at 10 Hz over the ipsilesional primary motor cortex (M1); (2) Low-frequency (LF) rTMS at 1 Hz over the contralesional M1; (3) sham rTMS. The primary outcome measure was a motor impairment score (Upper Extremity Fugl-Meyer) evaluated at baseline, after rTMS intervention, and at 3-month follow-up. Cortical excitability and functional magnetic resonance imaging (fMRI) data were obtained within 24 h before and after rTMS intervention. Analyses of variance were conducted to compare the recovery effects among the three rTMS groups, assessed using clinical, neurophysiological and fMRI tests.ResultsMotor improvement was significantly larger in the two rTMS groups than in the control group. The HF-rTMS group showed significantly increased cortical excitability and motor-evoked fMRI activation in ipsilesional motor areas, whereas the LF-rTMS group had significantly decreased cortical excitability and motor-evoked fMRI activation in contralesional motor areas. Activity in ipsilesional motor cortex significantly correlated with motor function, after intervention as well as at 3-month follow-up.ConclusionHF- and LF-rTMS can both improve motor function by modulating motor cortical activation in the early phase of stroke.

BackgroundMesenchymal stem cells (MSCs) are the most promising cell types for bone regeneration and repair due to their osteogenic potential. MSC differentiation is precisely regulated and orchestrated by the mechanical and molecular signals from the extracellular environment, involving complex pathways regulated at both the transcriptional and post-transcriptional levels. However, the potential role of long noncoding RNA (lncRNA) in the osteogenic differentiation of human MSCs remains largely unclear.MethodsHere, we undertook the survey of differential coding and noncoding transcript expression profiling and functional network analysis during osteogenic differentiation of human bone marrow mesenchymal stem cells (BMSCs) using human whole transcriptome microarray. The key pathways, mRNAs, and lncRNAs controlling osteogenic differentiation of BMSCs were identified by further bioinformatic analysis. The role of lncRNA in the osteogenic differentiation of MSCs was verified by lncRNA overexpression or knockdown methods.ResultsA total of 1269 coding transcripts with 648 genes significantly upregulated and 621 genes downregulated, and 1408 lncRNAs with 785 lncRNAs significantly upregulated and 623 lncRNAs downregulated were detected along with osteogenic differentiation. Bioinformatic analysis identified that several pathways may be associated with osteogenic differentiation potentials of BMSCs, such as the MAPK signaling pathway, the Jak-STAT signaling pathway, the Toll-like receptor signaling pathway, and the TGF-beta signaling pathway, etc. Bioinformatic analysis also revealed 13 core regulatory genes including seven mRNAs (GPX3, TLR2, BDKRB1, FBXO5, BRCA1, MAP3K8, and SCARB1), and six lncRNAs (XR_111050, NR_024031, FR374455, FR401275, FR406817, and FR148647). Based on the analysis, we identified one lncRNA, XR_111050, that could enhance the osteogenic differentiation potentials of MSCs.ConclusionsThe potential regulatory mechanisms were identified using bioinformatic analyses. We further predicted the interactions of differentially expressed coding and noncoding genes, and identified core regulatory factors by co-expression networks during osteogenic differentiation of BMSCs. Our results could lead to a better understanding of the molecular mechanisms of genes and lncRNAs, and their cooperation underlying MSC osteogenic differentiation and bone formation. We identified that one lncRNA, XR_111050, could be a potential target for bone tissue engineering.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0485-6) contains supplementary material, which is available to authorized users.

Periodontitis is a common intraoral infection and is inextricably linked to systemic diseases. Recently, the regulation between host immunologic response and periodontal pathogens has become a hotspot to explain the mechanism of periodontitis and related systemic diseases. Since Porphyromonas gingivalis ( P. gingivalis ) was proved as critical periodontal pathogen above all, researches focusing on the mechanism of its virulence factors have received extensive attention. Studies have shown that in the development of periodontitis, in addition to the direct release of virulent factors by periodontal pathogens to destroy periodontal tissues, over-low or over-high intrinsic immune and inflammatory response mediated by Toll-like receptors (TLRs) can lead to more lasting destruction of periodontal tissues. It is very necessary to sort out how various cytopathic factors of P. gingivalis mediate inflammation and immune responses between the host through TLRs so as to help precisely prevent, diagnose, and treat periodontitis in clinic. This review summarizes the role of three most widely studied pathogenic factors produced by P. gingivalis (lipopolysaccharide, gingipains, pili) and their interactions with TLRs at the cellular and molecular level in the progress of periodontitis.