Exosome-shuttled mitochondrial transcription factor A mRNA promotes the osteogenesis of dental pulp stem cells through mitochondrial oxidative phosphorylation activation.

OBJECTIVES: The treatment of bone defects by stem cells (MSCs) has achieved limited success over the recent few decades. The emergence of exosomes provides a new strategy for bone regeneration. Here, we aimed to investigate the effect and mechanisms of exosomes combined with dental pulp stem cells (DPSCs) on bone regeneration. MATERIALS AND METHODS: We isolated exosomes from stem cells from human exfoliated deciduous teeth (SHED) aggregates and evaluated the efficacy of exosomes combined with DPSCs in a cranial bone defect model. The potential mechanisms were further investigated. RESULTS: The effect of exosomes combined with DPSCs was remarkable on bone regeneration in vivo and exosomes promoted osteogenic differentiation of DPSCs in vitro. Mechanistically, exosomes increased the expression of mitochondrial transcription factor A (TFAM) in DPSCs by transferring TFAM mRNA. Moreover, highly expressed TFAM in DPSCs enhanced glutamate metabolism and oxidative phosphorylation (OXPHOS) activity. CONCLUSIONS: Consequently, exosomes strengthened bone regeneration of DPSCs through the activation of mitochondrial aerobic metabolism. Our study provides a new potential strategy to improve DPSC-based bone regenerative treatment.

RETRACTED: The effect of combined application of pentoxifylline and vitamin E for the treatment of osteoradionecrosis of the jaws: a meta-analysis.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the corresponding author and following a translated comparative examination of the two articles for similarity. It has been concluded that duplicate publication has occurred. The significantly duplicated article of the same title by same research team is: The effect of combined application of pentoxifylline and vitamin E for the treatment of osteoradionecrosis of the jaws: A meta-analysis Chin J Stomatol Res (Electronic Edition). August 2017, Vol.11, No.4. Both articles report on a meta-analysis study and focus on the treatment of osteoradionecrosis of the jaws by pentoxifylline combined with vitamin E, with search timeframe extending 2 years later in the retracted article.

Effects of auxin and ethylene on root growth adaptation to different ambient temperatures in Arabidopsis.

As sessile organisms, plants can modify their growth strategy in response to different temperatures, however very little is known about how roots growth responds to ambient temperature change. Here, we found that high temperature-induced root elongation is dependent on light intensity and the root growth of most TAA1 loss-of-function mutants is more sensitive to higher temperatures in Arabidopsis. TAA1 encodes a tryptophan aminotransferase which involved in the indole-3-pyruvic acid (IPA) pathway of indole-3-acetic acid (IAA) biosynthesis. The root elongation in ckrc1-1(one allele mutant of TAA1) is less sensitive to lower temperatures and more sensitive to higher temperatures than that of Col-0. By comparing the regulatory mechanisms of ckrc1-1 root growth at different temperatures (17 °C, 22 °C, and 27 °C), different interactions between signals (auxin and ethylene) and the effects of downstream genes were observed at different ambient temperatures in Arabidopsis. Lower temperature-enhanced ETR1-mediated ethylene signaling did not promote the expression of CKRC1, while higher temperature-enhanced signaling did. CKRC1 had an important role in the ACC inhibition of cell elongation at 22 °C and 27 °C but not at 17 °C. CKRC1-dependent auxin biosynthesis was critical for maintaining PIN1, PIN2, and AUX1 expression at lower temperatures. CKRC1, AUX1, and PIN2 regulated root elongation by affecting different regions of the root at different temperatures in Arabidopsis. Our experimental results suggested that changes in the in vivo signals at different temperatures were multi-layered in Arabidopsis.

Evaluation of a dual-wavelength size exclusion HPLC method with improved sensitivity to detect protein aggregates and its use to better characterize degradation pathways of an IgG1 monoclonal antibody.

The evaluation of a dual wavelength size exclusion high performance liquid chromatography (DW-SE-HPLC) method with improved sensitivity to detect aggregates in a high concentration IgG1 monoclonal antibody formulation is presented. This technique utilizes ultraviolet detection at two different wavelengths to monitor the levels of monomer, aggregate, and fragments and was shown to have improved sensitivity for the detection aggregates and fragments compared to light scattering (LS) detection. After assay optimization including the use of column conditioning, the limit of quantitation for aggregates was determined to be 0.04% with essentially complete recovery of aggregates from the column (>99.5%). The DW-SE-HPLC method was used to evaluate the level of protein aggregates generated by different environmental conditions such as exposure to elevated temperatures/acidic pH or intense light. The detection and characterization of protein aggregates by DW-SE-HPLC was compared with an orthogonal biophysical technique (sedimentation velocity analytical ultracentrifugation, SV-AUC). A good overall correlation was observed for levels of monomer, aggregates (dimer and multimers), and fragments as measured by the two analytical techniques (e.g., 6.0% vs. 5.3% and 14% vs. 11% for dimeric aggregates generated by elevated temperature/acidic pH and light exposure, respectively). The stability profile of a high concentration IgG1 monoclonal antibody formulation was investigated under stressed storage conditions (40 degrees C over 3 months) using the DW-SE-HPLC method including the loss of monomeric species with the concomitant accumulation of both aggregates and fragments. The nature and composition of the aggregates (primarily noncovalent dimers) and fragments (primarily loss of Fab from an intact IgG1) formed during storage were further characterized by a combination of LS measurements and mass spectroscopy analysis of deglycosylated IgG1 samples isolated by preparative SE-HPLC. The combination of DW-SE-HPLC, SV-AUC, LS, and mass spectroscopy results provided a detailed overall understanding the monomer, aggregate, fragment degradation pathway(s) for a high concentration IgG1 monoclonal antibody formulation during storage.