Abstract Liquid-chromatography coupled with high-resolution mass spectrometry (LC-HRMS) has become a workhorse in global metabolomics studies with growing applications across biomedical and environmental sciences. However, outstanding bioinformatics challenges in terms of data processing, statistical analysis and functional interpretation remain critical barriers to the wider adoption of this technology. To help the user community overcome these barriers, we have made major updates to the well-established MetaboAnalyst platform (www.metaboanalyst.ca). This protocol is part four of four and provides stepwise instructions on how to use MetaboAnalyst to conduct exploratory statistical analysis with complex metadata.
This study was to determine whether microRNA (miRNA)-126 regulates osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Rat BMSCs were extracted and stimulated for osteogenic differentiation. Functional experiments were conducted to assess miR-126’s impact on BMSCs differentiation. Western blot and RT-qPCR determined miR-126 expression. ALP activity detection and alizarin red staining detection were also performed. After osteogenic differentiation of BMSCs, miR-126 expression was gradually decreased over time. Overexpression of miR-26 decreased ALP activity, Notch signaling activity as well as declined Runx2 expression and calcium Salt nodules after treatment. Importantly, we found that Smad4 serves as a target of miR-126 while upregulation of the miRNA was accompanied with the decreased Smad4 protein expression without affecting the Smad4 mRNA level. In conclusion, miR-126 restrains osteogenic differentiation through inhibition of SMAD4 signaling, providing a novel insight into the mechanism.
Abstract Liquid-chromatography coupled with high-resolution mass spectrometry (LC-HRMS) has become a workhorse in global metabolomics studies with growing applications across biomedical and environmental sciences. However, outstanding bioinformatics challenges in terms of data processing, statistical analysis and functional interpretation remain critical barriers to the wider adoption of this technology. To help the user community overcome these barriers, we have made major updates to the well-established MetaboAnalyst platform (www.metaboanalyst.ca). This protocol is part one of four and provides stepwise instructions on how to use MetaboAnalyst to optimize parameters for LC-HRMS spectra processing. It may take ~2 hours to complete depending on the server load.
Abstract Background: The objective of this study was to explore the limit of orthodontic tooth movement by evaluating changes of alveolar bone during mandibular incisor retraction and comparing the bone modeling/tooth movement (B/T) ratio among patients with different vertical facial types. Methods: There were 103 patients with bimaxillary dentoalveolar protrusion evaluated with cephalograms in this study. The alveolar bone thickness (ABT) and cortical plate remodeling at cervical level (S1), middle level (S2) and apical level (S3) in Tip and Torque groups were measured, and B/T ratio in patients with different vertical facial types was calculated. Results: After excluding growth effect, buccolingual ABT at S1 and S2, as well as labial ABT at S1 in both Tip and Torque group decreased significantly. Cortical plate at three levels in Torque group remodeled to the lingual side. But in Tip group, cortical plate at S1 remodeled to the lingual side and cortical plate at S2 and S3 remodeled to the labial side. Regarding the B/T ratio, high-angle patients was smaller than average-angle and low-angle patients. Conclusions: In conclusion, resorption of alveolar bone was more than apposition during mandibular incisor retraction. The direction of alveolar cortical modeling was as same as tooth movement and the modeling amount was proportional to the distance of tooth movement. In addition, the B/T ratio was different among patients with different vertical craniofacial patterns. Close attention should be paid to high-angle patients with narrower ABT and smaller B/T ratio. Keywords: alveolar bone modeling, orthodontic tooth movement limit, incisor retraction, vertical facial patterns
IDH2 encodes a mitochondrial metabolic enzyme that converts isocitrate to α-ketoglutarate (α-KG) by reducing nicotinamide adenine dinucleotide phosphate (NADP+) to NADPH and participates in the citric acid cycle for energy production. Notably, this gene has been shown to be critical for cell proliferation. The abnormal expression of IDH2 has been reported in several types of cancer, and mutations in IDH2 have been identified in gliomas and acute myelogenous leukemia. The overexpression of IDH2 has been reported in endometrial, prostate and testicular cancer as well as in Kashin-Beck disease. In this study, we observed that IDH2 expression was significantly downregulated in early phase but was upregulated in advanced phase colon carcinoma compared to peritumoral tissues. In addition, we demonstrated that the growth of a colon carcinoma cell line was inhibited by IDH2-siRNA and increased following transfection with an IDH2-overexpressing plasmid. These results indicate that IDH2 may play a unique role in the development of colon carcinoma.
Abstract Liquid-chromatography coupled with high-resolution mass spectrometry (LC-HRMS) has become a workhorse in global metabolomics studies with growing applications across biomedical and environmental sciences. However, outstanding bioinformatics challenges in terms of data processing, statistical analysis and functional interpretation remain critical barriers to the wider adoption of this technology. To help the user community overcome these barriers, we have made major updates to the well-established MetaboAnalyst platform (www.metaboanalyst.ca). This protocol is part three of four and provides stepwise instructions on how to use MetaboAnalyst to integrate metabolomics data with transcriptomics data or to combine multiple metabolomics datasets.
A theoretical inverse relationship exists between osteogenic (bone forming) and adipogenic (fat forming) mesenchymal stem cell (MSC) differentiation. This inverse relationship in theory partially underlies the clinical entity of osteoporosis, in which marrow MSCs have a preference for adipose differentiation that increases with age. Two pro-osteogenic cytokines have been recently studied that each also possesses antiadipogenic properties: Sonic Hedgehog (SHH) and NELL-1 proteins. In the present study, we assayed the potential additive effects of the biologically active N-terminus of SHH (SHH-N) and NELL-1 protein on osteogenic and adipogenic differentiation of human primary adipose-derived stromal cell (hASCs). We observed that both recombinant SHH-N and NELL-1 protein significantly enhanced osteogenic differentiation and reduced adipose differentiation across all markers examined (alkaline phosphatase, Alizarin red and Oil red O staining, and osteogenic gene expression). Moreover, SHH-N and NELL-1 directed signaling produced additive effects on the pro-osteogenic and antiadipogenic differentiation of hASCs. NELL-1 treatment increased Hedgehog signaling pathway expression; coapplication of the Smoothened antagonist Cyclopamine reversed the pro-osteogenic effect of NELL-1. In summary, Hedgehog and Nell-1 signaling exert additive effects on the pro-osteogenic and antiadipogenic differentiation of ASCs. These studies suggest that the combination cytokines SHH-N+NELL-1 may represent a viable future technique for inducing the osteogenic differentiation of MSCs.
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