Obesity and dyslipidemia in patients with psoriasis: A case-control study.

The aim of this study was to conduct a more comprehensive analysis of the association between psoriasis and abnormal lipid metabolism.The case-control study included 222 psoriatic patients and 445 non-psoriatic control patients matched for age and gender. Clinical parameters included age, gender, and body mass index (BMI). Serum lipid levels were recorded and included cholesterol (CHO), triglycerides (TG), low-density lipoprotein (LDL), high density lipoprotein (HDL), phospholipids (PLIP), free fatty acids (FFA), lipoprotein (a) [Lp(a)], and apolipoproteins (apoA1, apoB, and apoE). Statistical analysis was carried out through the IBM Statistical Package for the Social Studies version 23.0.Compared with controls, levels of BMI and the prevalence of obesity were significantly higher in psoriatic patients. The results revealed that when compared to controls, significant elevation of serum TG (P <.001) and Lp(a) (P = .022) was observed. Levels of HDL (P <.001) and apoA1 (P <.001) were significantly lower in psoriatic patients. There was no significant difference in CHO (P = .367), LDL (P = .400), apoB (P = .294), apoE (P = .05), PLIP (P = .931) and FFA (P = .554) between patients and controls. The levels of CHO, TG, PLIP, FFA, and apoE were positively correlated with BMI level.Dyslipidemia was more common in psoriatic patients, compared with non-psoriatic controls.

Dynamic acetylation of the kinetochore-associated protein HEC1 ensures accurate microtubule-kinetochore attachment.

Faithful chromosome segregation during mitosis is critical for maintaining genome integrity in cell progeny and relies on accurate and robust kinetochore-microtubule attachments. The NDC80 complex, a tetramer comprising kinetochore protein HEC1 (HEC1), NDC80 kinetochore complex component NUF2 (NUF2), NDC80 kinetochore complex component SPC24 (SPC24), and SPC25, plays a critical role in kinetochore-microtubule attachment. Mounting evidence indicates that phosphorylation of HEC1 is important for regulating the binding of the NDC80 complex to microtubules. However, it remains unclear whether other post-translational modifications, such as acetylation, regulate NDC80-microtubule attachment during mitosis. Here, using pulldown assays with HeLa cell lysates and site-directed mutagenesis, we show that HEC1 is a bona fide substrate of the lysine acetyltransferase Tat-interacting protein, 60 kDa (TIP60) and that TIP60-mediated acetylation of HEC1 is essential for accurate chromosome segregation in mitosis. We demonstrate that TIP60 regulates the dynamic interactions between NDC80 and spindle microtubules during mitosis and observed that TIP60 acetylates HEC1 at two evolutionarily conserved residues, Lys-53 and Lys-59. Importantly, this acetylation weakened the phosphorylation of the N-terminal HEC1(1-80) region at Ser-55 and Ser-62, which is governed by Aurora B and regulates NDC80-microtubule dynamics, indicating functional cross-talk between these two post-translation modifications of HEC1. Moreover, the TIP60-mediated acetylation was specifically reversed by sirtuin 1 (SIRT1). Taken together, our results define a conserved signaling hierarchy, involving HEC1, TIP60, Aurora B, and SIRT1, that integrates dynamic HEC1 acetylation and phosphorylation for accurate kinetochore-microtubule attachment in the maintenance of genomic stability during mitosis.