👤 Mikhail O Lebedev

Visceral obesity plays a pivotal role in initiating and sustaining chronic systemic inflammation through complex interactions involving adipose tissue dysfunction, insulin resistance, immune system activation, and gut microbiome composition. Visceral obesity is also hypothesized to contribute to the development and progression of extraintestinal manifestations and complications in inflammatory bowel disease (IBD). The aim was to evaluate the interrelationships between ultrasound-measured visceral and subcutaneous adipose tissue thickness with carotid artery atherosclerosis indicators in IBD patients. The study included 90 patients with IBD aged 40-64 years. All patients underwent duplex ultrasound scanning of the carotid arteries with measurement of carotid plaque burden indicators. Ultrasound measurements of subcutaneous and visceral adipose tissue thickness (ATT) were performed: minimal subcutaneous adipose tissue thickness (mSATT), maximal preperitoneal adipose tissue thickness (mPATT), periumbilical subcutaneous adipose tissue thickness (PSATT), visceral abdominal adipose tissue thickness, peri- and pararenal adipose tissue thickness. Ultrasound-derived indicators of visceral obesity (mPATT and abdominal ATT), but not BMI or WC, were associated with an increased odds ratio for the presence of carotid plaque after adjustment for sex and age. Both mPATT and abdominal ATT demonstrated positive correlations with apoB concentration, LDL-C, sdLDL, eLDL-TG, and inverse correlations with adiponectin concentration. In patients with IBD aged 40-64 years, visceral adipose tissue thickness measured by ultrasound and WC were associated with the carotid plaque burdens. Ultrasound-measured mPATT and abdominal ATT, but not BMI and WC, were independently associated with carotid atherosclerosis in patients with IBD. Show less

The Drosophila Nonspecific Lethal (NSL) complex is a major transcriptional regulator of housekeeping genes. It contains at least seven subunits that are conserved in the human KANSL complex: Nsl1/Wah (KANSL1), Dgt1/Nsl2 (KANSL2), Rcd1/Nsl3 (KANSL3), Rcd5 (MCRS1), MBD-R2 (PHF20), Wds (WDR5) and Mof (MOF/KAT8). Previous studies have shown that Dgt1, Rcd1 and Rcd5 are implicated in centrosome maintenance. Here, we analyzed the mitotic phenotypes caused by RNAi-mediated depletion of Rcd1, Rcd5, MBD-R2 or Wds in greater detail. Depletion of any of these proteins in Drosophila S2 cells led to defects in chromosome segregation. Consistent with these findings, Rcd1, Rcd5 and MBD-R2 RNAi cells showed reduced levels of both Cid/CENP-A and the kinetochore component Ndc80. In addition, RNAi against any of the four genes negatively affected centriole duplication. In Wds-depleted cells, the mitotic phenotypes were similar but milder than those observed in Rcd1-, Rcd5- or MBD-R2-deficient cells. RT-qPCR experiments and interrogation of published datasets revealed that transcription of many genes encoding centromere/kinetochore proteins (e.g., cid, Mis12 and Nnf1b), or involved in centriole duplication (e.g., Sas-6, Sas-4 and asl) is substantially reduced in Rcd1, Rcd5 and MBD-R2 RNAi cells, and to a lesser extent in wds RNAi cells. During mitosis, both Rcd1-GFP and Rcd5-GFP accumulate at the centrosomes and the telophase midbody, MBD-R2-GFP is enriched only at the chromosomes, while Wds-GFP accumulates at the centrosomes, the kinetochores, the midbody, and on a specific chromosome region. Collectively, our results suggest that the mitotic phenotypes caused by Rcd1, Rcd5, MBD-R2 or Wds depletion are primarily due to reduced transcription of genes involved in kinetochore assembly and centriole duplication. The differences in the subcellular localizations of the NSL components may reflect direct mitotic functions that are difficult to detect at the phenotypic level, because they are masked by the transcription-dependent deficiency of kinetochore and centriolar proteins. Show less