The incidence of multiple sclerosis (MS) has increased in recent years. Its pathogenesis involves the interaction between various elements, with interleukin 27 (IL-27) playing a key role in autoimmuni Show more
The incidence of multiple sclerosis (MS) has increased in recent years. Its pathogenesis involves the interaction between various elements, with interleukin 27 (IL-27) playing a key role in autoimmunity. The presence of the IL-27 receptor on astrocytes emphasizes its involvement in the disease's progression. The study aims to investigate possible associations between IL27 rs181206, serum level of IL27, and the development of MS. The study comprised 70 MS patients and 70 seemingly healthy controls. They were genotyped for IL27 rs181206 using the Taqman allelic discrimination approach, and their serum IL27 levels were estimated using ELISA. The frequency of TT genotype, T allele, and IL27 serum level were significantly higher among MS patients compared to controls. There was no significant difference between IL27 serum levels among different genotypes in both MS patients and controls; however, individuals with TT genotype showed higher levels of IL27 than those with CC genotype. TT genotype and T allele can increase the risk of developing MS. On the other hand, carrying the C allele may be associated with a lower risk of MS development. Understanding IL27 genetics and epistatic interactions can help clarify IL27's role in MS pathogenesis and utilize it as a therapeutic target. Show less
Solid-tubulocystic variant of intrahepatic cholangiocarcinoma (ST-iCCA) is newly described entity characterized by two distinct histologic growth patterns: (1) solid sheets of tumor cells with focal n Show more
Solid-tubulocystic variant of intrahepatic cholangiocarcinoma (ST-iCCA) is newly described entity characterized by two distinct histologic growth patterns: (1) solid sheets of tumor cells with focal necrosis giving pseudopapillary appearance and (2) tubular or pseudoglandular structures containing pink, colloid-like material. Tumor cells are inhibin-positive and harbor NIPBL::NACC1 fusion gene. To date, only 28 cases of ST-iCCA have been documented. While prior molecular studies provided insights into ST-iCCA, genetic profiles of individual histologic components have not been explored. This study presents first transcriptomic analysis comparing the solid/pseudopapillary and pseudoglandular components of ST-iCCA. Two cases of histologically confirmed ST-iCCA were identified for RNA sequencing which was performed on solid/pseudopapillary component, pseudoglandular component, and normal tissue. Analysis revealed distinct gene expression profiles for each pattern. Solid/pseudopapillary component uniquely overexpressed DMRTA1, NEXMIF, PRDM6, SORCS3, and NALF, while pseudoglandular component exhibited unique overexpression of HRG, ITIH3, TAT, APOA2, CP, ALDOB, CPS1, F2, KHG1, SERPINC1, HPX, C9, ADGRF1, MUC21, SAA2, SPRR2A, SAA1, FGL1, CFHR1, and LBP. These findings establish unique gene signatures for these variants of ST-iCCA, providing potential biomarkers for differential diagnosis, prognosis and targeted therapy. The distinct genetic profiles may also uncover novel therapeutic targets to address the aggressive nature of ST-iCCA. Show less