👤 Theo M de Kok

Cardiovascular and metabolic disorders, particularly diabetes and obesity, are highly prevalent in the Middle East and North Africa (MENA) region, exhibiting some of the highest global incidence rates. These conditions significantly increase the severity of infectious diseases, notably COVID-19, leading to a rise in long-COVID cases among affected individuals. Furthermore, the MENA region's extreme temperatures exacerbate cardiovascular issues by elevating heart rates and blood pressure, increasing dehydration and blood viscosity. Extracorporeal therapies, such as apheresis, effectively reduces plasma lipids and inflammatory markers. Furthermore, apheresis has shown promise in reducing autoantibodies associated to long-COVID. Our previous research indicated that apheresis alleviates symptoms in patients with long-COVID and chronic fatigue syndrome. In this study, we treated 24 male patients from the MENA region suffering from chronic fatigue and/or different metabolic diseases such as diabetes, dyslipidemia, or obesity, using double filtration plasmapheresis. Comprehensive plasma analyses were performed before and after apheresis to assess lipid profiles, inflammatory markers, and autoantibodies, revealing significant changes following the procedure. Genetic analyses on a subgroup of the patients showed no mutations in the LDLR, APOB, APOE, PCSK9, LIPA, and LDLRAP1 genes known to be associated with predispositions to monogenic lipid disorders. However, all patients in this subgroup demonstrated an intermediate to high likelihood that their elevated lipid levels have a polygenic basis. These findings suggest that implementing apheresis in the MENA region could significantly improve health outcomes and life expectancy for affected individuals. Show less

This study investigated the impact of alterations in six key genes ( Genomic data from five datasets were merged to identify 437 ESCC patients, categorized into altered ( The altered group exhibited a significantly higher tumor mutational burden (TMB) and mutation count than the unaltered group ( This study highlights that genomic alterations in these six genes are associated with poorer OS in ESCC, despite higher TMB potentially increasing tumor neo-antigens. These findings underscore the need for further research to explore their prognostic and therapeutic potential. Show less

Particulate matter (PM) exposure leads to premature death, mainly due to respiratory and cardiovascular diseases. Identification of transcriptomic biomarkers of air pollution exposure and effect in a healthy adult population. Microarray analyses were performed in 98 healthy volunteers (48 men, 50 women). The expression of eight sex-specific candidate biomarker genes (significantly associated with PM Average long-term PM Expression of the sex-specific candidate genes identified in the discovery population predicted PM Show less

In searching for a tumor suppressor gene in the 3p21.3 region, we isolated two genes, RBM5 and RBM6. Sequence analysis indicated that these genes share similarity. RBM5 and-to a lesser extent-RBM6 also have similarity to DXS8237E at Xp11.3-11.23, which maps less than 20 kb upstream of UBE1. A homologue of UBE1, UBE1L, is located at 3p21. 3. FISH analysis showed that the distance between UBE1L and RBM5 in 3p21.3 is about 265 kb. DXS8237E and UBE1 on the X chromosome have the same orientation, whereas on chromosome 3 the orientation of RBM5 and that of RBM6 are opposite to the orientation of UBE1L. Presumably, part of the Xp11.3-11.23 region has duplicated to chromosome 3. Part of this region on chromosome 3 may subsequently have duplicated again within the same chromosomal region. Inversion at some stage of the evolution of the human genome would explain the change in orientation of the genes on chromosome 3 compared with that of the genes on the X chromosome. Show less

In the search for a tumour suppressor gene in the 3p21.3 region we isolated two genes, RBM5 and RBM6. Gene RBM5 maps to the region which is homozygously deleted in the small cell lung cancer cell line GLC20; RBM6 crosses the telomeric breakpoint of this deletion. Sequence comparison revealed that at the amino acid level both genes show 30% identity. They contain two zinc finger motifs, a bipartite nuclear signal and two RNA binding motifs, suggesting that the proteins for which RBM5 and RBM6 are coding have a DNA/RNA binding function and are located in the nucleus. Northern and Southern analysis did not reveal any abnormalities. By SSCP analysis of 16 lung cancer cell lines we found only in RBM5 a single presumably neutral mutation. By RT-PCR we demonstrated the existence of two alternative splice variants of RBM6, one including and one excluding exon 5, in both normal lung tissue and lung cancer cell lines. Exclusion of exon 5 results in a frameshift which would cause a truncated protein of 520 amino acids instead of 1123 amino acids. In normal lung tissue, the relative amount of the shorter transcript was much greater than that in the lung tumour cell lines, which raises the question whether some tumour suppressor function may be attributed to the derived shorter protein. Show less