5 research outputs found
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TET2 facilitates PPARĪ³ agonistāmediated gene regulation and insulin sensitization in adipocytes
Emerging evidence indicates that epigenetic mechanisms like DNA methylation directly contribute to metabolic regulation. For example, we previously demonstrated that de novo DNA methyltransferase Dnmt3a plays a causal role in the development of adipocyte insulin resistance. Recent studies suggest that DNA demethylation plays an important role in the developmental process of adipocytes. However, little is known about whether DNA demethylase ten-eleven translocation (TET) proteins regulate the metabolic functions of adipocytes.MethodsThe expression of Tet genes was assessed in the fractionated adipocytes of chow- and high fat diet-fed C57/Bl6 mice using qPCR and western blotting. The effect of Tet2 gain- or loss-of-function in fully mature 3T3-L1 adipocytes in the presence/absence of Rosiglitazone (Rosi) and TNF-Ī± on insulin sensitivity was using the insulin-stimulated glucose uptake and insulin signaling assays. Gene expression and DNA methylation analyses of PPARĪ³ target genes was performed in the same setting. In addition, PPARĪ³ reporter assays, co-immunoprecipitation assays, PPARĪ³ ChIP-PCR analyses were performed.ResultsWe found that adipose expression of TET2, alone among its family members, was significantly reduced in diet-induced insulin resistance. TET2 gain-of-function was sufficient to promote insulin sensitivity while loss-of-function was necessary to facilitate insulin sensitization in response to the PPARĪ³ agonist Rosiglitazone (Rosi) in cultured adipocytes. Consistent with this, TET2 was required for Rosi-dependent gene activation of certain PPARĪ³ targets accompanied by changes in DNA demethylation at the promoter regions. Furthermore, TET2 was necessary to sustain PPARĪ³ binding to target loci upon activation with Rosi via physical interaction with PPARĪ³.ConclusionsOur data demonstrate that TET2 works as an epigenetic regulator of Rosi-mediated insulin sensitization and transcriptional regulation in adipocytes
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Primary Spinal Infections in Patients With Hematologic Immunocompromising Conditions: A Systematic Literature Review
PurposePrimary spinal infections (PSIs) are a group of infectious diseases characterized by inflammation of the end plate-disk unit or its surroundings. PSI is considered more prevalent and aggressive among patients with chronic immunocompromised states. Association of PSIs, immunocompromising cancers, and hemoglobinopathies has not been systematically analyzed. We conducted a systematic review to study characteristics, clinical presentation, and mortality of patients with PSI in the setting of hematologic disease.MethodsA systematic literature search in PubMed, Web of Science, and Scopus was conducted in April 2022 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included retrospective case series and individual case reports.ResultsOn careful review, 28 articles published between 1970 and 2022 were selected. These studies featured 29 patients who met inclusion criteria (mean age 29 years, age range 1.5 to 67 years; 63.3% male). Lumbar infection was the most common location (65.5%), with Salmonella (24.1%) as the main causative microorganism. Neurologic compromise was present in 41% of patients, and surgical intervention occurred in 48.3%. Average antibiotic duration was 13 weeks. The postoperative complication rate was 21.4%, with a mortality of 6.9%.ConclusionPSI in patients with hematologic disease, while having shorter periods to diagnosis, presents increased rates of neurologic deficit, surgical intervention, and complications
Citation analysis of the most influential ependymoma research articles illustrates improved knowledge of the molecular biology of ependymoma.
The history of academic research on ependymoma is expansive. This review summarizes its history with a bibliometric analysis of the 100 most cited articles on ependymoma. In March 2020, we queried the Web of Science database to identify the most cited articles on ependymoma using the terms "ependymoma" or "ependymal tumors," yielding 3145 publications. Results were arranged by the number of times each article was cited in descending order. The top 100 articles spanned across nearly a century; the oldest article was published in 1924, while the most recent was in 2017. These articles were published in 35 unique journals, including a mix of basic science and clinical journals. The three institutions with the most papers in the top 100 were St. Jude Children's Research Hospital (16%), the University of Texas MD Anderson Cancer Center (6%), and the German Cancer Research Center (5%). We analyzed the publications that may be considered the most influential in the understanding and treatment management of ependymoma. Studies focused on the molecular classification of ependymomas were well-represented among the most cited articles, reflecting the field's current area of focus and its future directions. Additionally, this article also offers a reference for further studies in the ependymoma field