Translational research : the journal of laboratory and clinical medicine
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CDKN2C/p18 (Cyclin-Dependent Kinase Inhibitor 2C) is a cell growth regulator that controls cell cycle progression and has previously been associated with increased risk for type II diabetes (T2D) and reduced peripheral adipose tissue (AT) storage capacity. This study explored the role of CDKN2C in AT lipid and glucose metabolism in T2D. Expression of CDKN2C and other genes was analyzed by transcriptomics, or real-time PCR in subcutaneous AT (SAT) samples obtained from T2D and control subjects matched for sex, age and BMI and also in paired SAT and omental AT (OAT) samples. ⋯ Knockdown of CDKN2C did not affect the percentage of differentiating cells compared to wild type cultures. However, CDKN2C knockdown cultures had significantly lower expression of differentiation markers CEBPA, ADIPOQ and FASN and transiently reduced lipid accumulation per adipocyte during differentiation. Our findings suggest that adipose CDKN2C expression might be reduced as a consequence of insulin resistance and obesity, and this can further contribute to impairment of SAT lipid storage.
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Meta Analysis
Differential Expression of Members of SOX Family of Transcription Factors in Failing Human Hearts.
The Sry-related high-mobility-group box (SOX) gene family, with 20 known transcription factors in humans, plays an essential role during development and disease processes. Several SOX proteins (SOX4, 11, and 9) are required for normal heart morphogenesis. SOX9 was shown to contribute to cardiac fibrosis. ⋯ Using a meta-analysis combining epigenetics and genome-wide association data, we reported several genomic variants associated with HF phenotype linked to SOX4 or SOX8. In summary, our results implicate that SOX4 and SOX8 have a role in cardiomyopathy, leading to HF in humans. The molecular mechanism associated with them in HF warrants further investigation.
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The rapid development of two nucleoside-modified mRNA vaccines that are safe and highly effective against coronavirus disease 2019 has transformed the vaccine field. The mRNA technology has the advantage of accelerated immunogen discovery, induction of robust immune responses, and rapid scale up of manufacturing. Efforts to develop genital herpes vaccines have been ongoing for 8 decades without success. ⋯ While these goals have been elusive, new efforts with nucleoside-modified mRNA-lipid nanoparticle vaccines show great promise. We review past approaches to vaccine development that were unsuccessful or partially successful in large phase 3 trials, and describe lessons learned from these trials. We discuss our trivalent mRNA-lipid nanoparticle approach for a prophylactic genital herpes vaccine and the ability of the vaccine to induce higher titers of neutralizing antibodies and more durable CD4+ T follicular helper cell and memory B cell responses than protein-adjuvanted vaccines.