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Background β-catenin mutations that constitutively activate the canonical Wnt signaling have been observed in a subset of hepatocellular carcinomas (HCCs). These mutations are associated with chromosomal stability, low histological grade, low tumor invasion and better patient survival. We hypothesized that canonical Wnt signaling is selectively activated in well-differentiated, but repressed in poorly differentiated HCCs. To this aim, we characterized differentiation status of HCC cell lines and compared their expression status of Wnt pathway genes, and explored their activity of canonical Wnt signaling. Results We classified human HCC cell lines into \"well-differentiated\" and \"poorly differentiated\" subtypes, based on the expression of hepatocyte lineage, epithelial and mesenchymal markers. Poorly differentiated cell lines lost epithelial and hepatocyte lineage markers, and overexpressed mesenchymal markers. Also, they were highly motile and invasive. We compared the expression of 45 Wnt pathway genes between two subtypes. TCF1 and TCF4 factors, and LRP5 and LRP6 co-receptors were ubiquitously expressed. Likewise, six Frizzled receptors, and canonical Wnt3 ligand were expressed in both subtypes. In contrast, canonical ligand Wnt8b and noncanonical ligands Wnt4, Wnt5a, Wnt5b and Wnt7b were expressed selectively in well- and poorly differentiated cell lines, respectively. Canonical Wnt signaling activity, as tested by a TCF reporter assay was detected in 80% of well-differentiated, contrary to 14% of poorly differentiated cell lines. TCF activity generated by ectopic mutant β-catenin was weak in poorly differentiated SNU449 cell line, suggesting a repressive mechanism. We tested Wnt5a as a candidate antagonist. It strongly inhibited canonical Wnt signaling that is activated by mutant β-catenin in HCC cell lines. Conclusion Differential expression of Wnt ligands in HCC cells is associated with selective activation of canonical Wnt signaling in well-differentiated, and its repression in poorly differentiated cell lines. One potential mechanism of repression involved Wnt5a, acting as an antagonist of canonical Wnt signaling. Our observations support the hypothesis that Wnt pathway is selectively activated or repressed depending on differentiation status of HCC cells. We propose that canonical and noncanonical Wnt pathways have complementary roles in HCC, where the canonical signaling contributes to tumor initiation, and noncanonical signaling to tumor progression.

Essential thrombocythemia (ET) is a myeloproliferative disorder with elevated numbers of thrombocytes and facioscapulohumeral muscular dystrophy (FSHD) is the third most common dystrophy among all dystrophies. In this paper, we report a novel case of FSHD coinciding with ET.

Background The role of genetic variants in Mucin-5B (MUC5B) and telomerase reverse transcriptase (TERT) in idiopathic pulmonary fibrosis (IPF) pathogenesis, as well as their associations with clinical characteristics, remain uncertain and may exhibit ethnic variations. Methods This single-center, cross-sectional study aimed to investigate the distribution of MUC5B rs35705950 and TERT rs2736100 variants among Turkish IPF patients. Additionally, we assessed associations between these genetic variants and clinical parameters including gender-age-physiology (GAP) score, percent predicted forced vital capacity (FVC%), percent predicted diffusing capacity for carbon monoxide (DLCO%), and the presence of honeycombing on high-resolution computed tomography (HRCT). Results The allele frequency of the TERT rs2736100 variant showed no significant difference between IPF patients and healthy controls (41.7% vs. 43.7%, OR = 0.92, p  = 0.73). Conversely, the allele frequency of the MUC5B rs35705950 variant was significantly higher in IPF patients compared to controls (39.6% vs. 12%, OR = 4.81, p  = 0.0001). IPF patients carrying the homozygous MUC5B variant (TT) exhibited significantly higher mean FVC% values than those without the variant (GG) (82.2% vs. 71.7%, respectively; p  = 0.004). Furthermore, the mean age at diagnosis was significantly older in IPF patients carrying at least one T allele of the MUC5B variant (GT + TT) compared to non-carriers (GG) (67.7 years vs. 62.3 years, respectively; p  = 0.013). Conclusions Our findings indicate that the MUC5B rs35705950 variant is significantly associated with increased IPF susceptibility among Turkish patients. In contrast, the TERT rs2736100 variant was not linked to IPF risk. Additionally, the presence of the MUC5B rs35705950 variant correlated with later disease onset and relatively preserved pulmonary function in this patient population.

Background Many studies have revealed that microRNA (miRNA) molecules may take part in idiopathic pulmonary fibrosis (IPF). But, the role of miRNAs in the development of IPF is not yet clear. Methods We investigated the plasma levels of miR-21, miR-590, miR-192, and miR-215 in IPF (n = 88) and healthy control (n = 20) groups in this study. We compared the expression levels of target miRNAs in patients with IPF and healthy participants. We grouped the patients with IPF according to age, forced vital capacity, carbon monoxide diffusing capacity (DLCO), gender-Age-pulmonary physiology (GAP) score, the presence of honeycombing and compared the expression levels of target miRNAs in these clinical subgroups. Results 82 (93.18%) of the patients with IPF were male and the mean age was 66.6 ± 8.6 years. There was no significant difference between the gender and age distributions of IPF and the control group. The mean plasma miR-21 and miR-590 levels in IPF group were significantly higher than in the control group (p < 0.0001, p < 0.0001, respectively). There was no significant difference between the miR-192 and miR-215 expression levels of the IPF and control group. Both miR-21 and miR-590 correlated positively with age (p = 0.041, p = 0.007, respectively) while miR-192 and miR-215 displayed a negative correlation with age (p = 0.0002, p < 0.0001, respectively). The levels of miR-192 and miR-215 increased as the GAP score decreased. The levels of miR-192 in patients with honeycombing were significantly lower than in those without honeycombing (p = 0.003). Conclusions Our study showed that both miR-21 and miR-590 were overexpressed in IPF. The miR-21 and miR-590 were associated with DLCO, while miR-192 and miR-215 were associated with the GAP score and honeycombing.

This study presents an adult 7p21 deletion patient, including a literature review specific to 7p21 deletion, and concludes recommendations toward such patients. A 47-year-old male with moderate-to-severe learning disability and significant dysmorphic features was seen in our Medical Genetics clinic. Initially, a chromosome analysis was requested considering a pre-diagnosis of Down syndrome with adult age, and other chromosomal abnormalities. In karyotype analysis, one chromosome 7 was observed to have a deletion on its short arm. Subsequently, single nucleotide polymorphism array (SNP Array) analysis was pursued to confirm the abnormality seen in the chromosome analysis and to elucidate its details. The results indicated a 16-megabase loss in the 7p21.3-p15.3 regions.

Multiple pterygium syndrome is characterized by a number of phenotypic features, small stature, webbing of the neck, elbows, and/or knees, and joint contractures. In this report, we present an 11-year-old boy who had the classical findings of multiple pterygium syndrome, and his chromosomal analysis revealed a 47,XXY karyotype. Interestingly, he did not show any of the main clinical signs of Klinefelter syndrome. This patient appears to be the first reported case in the literature in which a non-mosaic 47,XXY karyotype has been found in a patient with multiple pterygium syndrome. The aim of the present report is to describe a non-classic Klinefelter syndrome associated with multiple pterygium syndrome and to emphasize the importance of karyotype analysis in patients with multiple pterygium syndrome.

Hepatosellüler karsinoma (HCC) vasküler bir tümördür ve hipoksi HCC gelişiminde ve ilerleyişinde önemli bir anjiyogenik faktördür. Hipoksi tarafından uyarılan birçok faktör tümör hücrelerini ve komşu hücreleri etkileyerek, tümörün daha agresif olmasına ve tedavi direncine neden olmaktadır. Bu faktörlerden birisi olan hepatosit büyüme faktörünün (HGF) karaciğer hücrelerinin büyüme ve farklılaşmasında önemli bir rolü olduğu bilinmektedir. HGF ve reseptörü olan c-Met ekspresyonunun hipoksik koşullarda arttığı belirlenmiştir. Ancak HCC gelişimi, ilerleyişi ve tedavi yanıtında HGF/cMet yolağının rolü tam olarak bilinmemektedir.Çalışmamızda HGF/c-Met yolağı aktivasyonunun, HCC hücrelerinin hipoksi yanıtında ve radyoterapi direncinde rolü olabileceği düşüncesi ile HGF/c-Met yolağı aktivasyonu ile hipoksik koşullarda hücre sağ kalımını, hücre motilite ve invazyonunu, HİF ve HİF aracılı gen ekspresyonlarını ve HCC hücrelerinin radyasyon uygulamasına yanıtlarının nasıl etkilendiğini araştırdık.Sonuçlarımız HCC hücre dizilerinde HGF/c-Met sinyal ileti yolağının hipoksi ve radyasyon ile uyarılabildiğini göstermektedir. Hipoksi ve / veya HGF uygulaması hücre canlılığını değiştirmemekte ancak motilite ve invazyonda belirgin artışa neden olmaktadır. HCC hücrelerinde radyasyon stresine verilen yanıt erken dönemde motilite artışı şeklinde olmakta geç dönemde ise hücre canlılığı etkilenmektedir. Radyasyon uygulaması öncesinde hücrelerin hipoksi ve / veya HGF ile uyarılmaları halinde canlılıklarında, motilite ve invazyonlarında belirgin artış olduğu görülmüştür.Bu veriler HCC hücrelerinin malign fenotip kazanmalarında özellikle invazyon ve metastaz sürecinde HGF/c-Met yolağı aktivasyonunun önemli rol oynadığını göstermektedir. Bu etkiyi gerçekleştirmesinde hipoksi tarafından uyarılan HIF aktivasyonu ve VEGF, EPO, integrin gen ekspresyonlarındaki artış önemli olabilir. Elde ettiğimiz veriler HCC hücrelerindeki radyasyon direncinin gelişmesinde HGF ve hipoksi tarafından uyarılan genlere ek olarak MT1-MMP ve Rlip76’nın da rolü olabileceğini düşündürmektedir.