Thymic Epithelial Neoplasms: Focusing on the Epigenetic Alterations

Thymic Epithelial Neoplasms (TENs) represent the most common tumors of the thymus gland. Epigenetic alterations are generally involved in initiation and progression of various cancer entities. However, little is known about the role of epigenetic modifications in TENs. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The search terms thymoma, thymic carcinoma, thymic epithelial neoplasm, epigenetics, DNA methylation, HDAC and miRNA were employed and we were able to identify forty studies focused on TENs and published between 1997 and 2021. Aberrant epigenetic alterations seem to be involved in the tumorigenesis of thymomas and thymic carcinomas, with numerous studies reporting on non-coding RNA clusters and altered gene methylation as possible biomarkers in different types of TENs. Interestingly, Histone Deacetylase Inhibitors have shown potent antitumor effects in clinical trials, thus possibly representing effective epigenetic therapeutic agents in TENs. Additional studies in larger patient cohorts are, nevertheless, needed to verify the clinical utility and safety of novel epigenetic agents in the treatment of patients with TENs.     

The EPH/Ephrin System in Gynecological Cancers: Focusing on the Roots of Carcinogenesis for Better Patient Management

Gynecological cancers represent some of the most common types of malignancy worldwide. Erythropoietin-producing hepatocellular receptors (EPHs) comprise the largest subfamily of receptor tyrosine kinases, binding membrane-bound proteins called ephrins. EPHs/ephrins exhibit widespread expression in different cell types, playing an important role in carcinogenesis. The aim of the current review was to examine the dysregulation of the EPH/ephrin system in gynecological cancer, clarifying its role in ovarian, endometrial, and cervical carcinogenesis. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The search terms ephrin, ephrin receptor, ovarian cancer, endometrial cancer, and cervical cancer were employed and we were able to identify 57 studies focused on gynecological cancer and published between 2001 and 2021. All researched ephrins seemed to be upregulated in gynecological cancer, whereas EPHs showed either significant overexpression or extensive loss of expression in gynecological tumors, depending on the particular receptor. EPHA2, the most extensively studied EPH in ovarian cancer, exhibited overexpression both in ovarian carcinoma cell lines and patient tissue samples, while EPHB4 was found to be upregulated in endometrial cancer in a series of studies. EPHs/ephrins were shown to exert their role in different stages of gynecological cancer and to influence various clinicopathological parameters. The analysis of patients’ gynecological cancer tissue samples, most importantly, revealed the significant role of the EPH/ephrin system in the development and progression of gynecological cancer, as well as overall patient survival. In conclusion, the EPH/ephrin system represents a large family of biomolecules with promising applications in the fields of diagnosis, prognosis, disease monitoring, and treatment of gynecological cancer, with an established important clinical impact.     

Investigating the relationship between the hair fiber proteome and hair quality

Many hair characteristics (e.g. color and curl) are genetically determined. Here, we investigated whether hair quality is also genetically controlled and related to differences in hair composition. Female, Caucasian subjects ( n  = 292) were recruited into this study and segmented by self-perceived hair quality and by permanent colorant usage. Hair fibers were collected and characterized by amino acid analysis, dry tensile elastic modulus testing and two-dimensional electrophoresis of hair protein extracts.
Protein analysis revealed a string of 66 kDa proteins that correlated with hair of high quality. Loss of low molecular weight (14–29 kDa) proteins increased with colorant usage, particularly in hair of low quality. Amino acid analysis showed that the levels of serine and threonine across all the subjects followed bimodal frequency distributions suggestive of a genetic influence. Overall, data suggested that perception of quality was linked to high serine and threonine levels. In addition, where hair was colored, quality was associated with lower cysteic acid levels. Lower cysteic acid levels were not linked to lower colorant usage and our data suggest that high quality hair may be more resistant to colorant damage. Elastic modulus was significantly higher in hair of higher quality (4.65 GPa) compared to all medium and low quality hair combined (4.3 GPa), P  < 0.02. This suggests a link between altered hair composition and mechanical properties. In conclusion, the composition and mechanical properties of hair have been linked to hair quality. We hypothesize that hair quality is thus likely to be genetically determined. Understanding of the links between hair composition and its properties could be utilized in the future for designing products targeted to each individual's hair make-up, and for producing diagnostic tools for determining hair quality.     

Genetic Variability and Phylogeny of High Risk HPV Type 16, 18, 31, 33 and 45 L1 Gene in Greek Women

The present study explores nucleotide variability, phylogeny and association with cervical neoplasia in high risk HPV types 16, 18, 31, 33 and 45 collected from Greek women. Of the 1894 women undergoing routine cervical cytology examination, 160 samples test positive for single infections of HPV type 16 (n = 104), HPV 31 (n = 40), HPV 33 (n = 7), HPV 18 (n = 5), and HPV 45 (n = 4) were typed by microarrays method, amplified by PCR then sequenced and phylogenetically analyzed. For HPV 16, 9 variants with nucleotide variations were included into the study. For HPV 31, 33, 18 and 45, nucleotide variations were identified in 6, 4, 2 and 3 variants, respectively. The Bayesian inference and Maximum Parsimony methods were used in order to construct the phylogenetic trees. When types were analyzed independently HPV 16 (European and non-European) and HPV 18 (African and non-African) formed distinct clades. The genomic characterization of HPV variants will be important for illuminating the geographical relatedness and biological differences and for the determination of their risk.     

Apolipoprotein E epsilon4 allele as a genetic risk factor for left ventricular failure in homozygous beta-thalassemia

In homozygous beta-thalassemia, the organ damage is mainly attributed to excessive iron deposition through the formation of oxygen free radicals. Despite appropriate transfusion and chelation therapy and low ferritin levels, patients still develop organ failure, heart failure being the main cause of death. This study was designed to determine whether the decreased antioxidant activity of the apolipoprotein E (APOE) 4 allele could represent a genetic risk factor for the development of left ventricular failure (LVF) in beta-thalassemia homozygotes. A total of 251 Greek beta-thalassemia homozygotes were studied. Patients were divided in three groups: group A (n = 151) with no cardiac impairment, group C (n = 47) with LVF, and 53 patients with LV dilatation and normal LV systolic function constituted the group B. DNA was obtained from all patients, and the polymerase chain reaction was used to analyze the polymorphism at the APOE locus. The APOE allele frequencies were compared with those of a Greek control sample of 216 healthy blood donors. Patients with no cardiac impairment had an APOE 4 allele frequency (7.9%) not different from population controls (6.5%, P > .05), while patients with LVF had a significantly higher frequency of APOE 4 (12.8%) than the controls (P < .05, odds ratio = 2.11, 95% confidence interval 1.03 to 4.32). The APOE 4 allele may represent an important genetic risk factor for the development of organ damage in homozygous beta-thalassemia.     

Physicochemical,textural and sensory properties of white soft cheese made from buffalo and cow milk mixtures

The physicochemical, textural and sensory properties of white soft cheeses made from three different buffalo and cow milk mixtures (100:0, 70:30 and 30:70) during 3‐month storage were studied. The increase in buffalo milk concentration resulted in increasing total cheese yield, dry matter (DM) and fat retention and fat in DM content. However, it caused reductions in moisture content, salt intake, hardness, chewiness, elasticity, sensory hardness and sensory cohesiveness of the samples. The percentage of water‐soluble nitrogen to total nitrogen increased during storage resulting in decreased fracturability, hardness (textural and sensory), cohesiveness (textural and sensory), springiness, chewiness and elasticity. The panellists evaluated the white soft cheese made with buffalo milk as the most acceptable.     

The p.Pro482Ala Variant in the CNNM2 Gene Causes Severe Hypomagnesemia Amenable to Treatment with Spironolactone

Renal hypomagnesemia syndromes involving CNNM2 protein pathogenic variants are associated with variable degrees of neurocognitive dysfunction and hypomagnesemia. Here, we report a family with a novel CNNM2 p.Pro482Ala variant, presenting with overt hypomagnesemia and mild neurological involvement (autosomal dominant renal hypomagnesemia 6, HOMG6, MIM# 613882). Using a bioinformatics approach, we showed that the p.Pro482Ala amino acid substitution causes a 3D conformational change in CNNM2 structure in the cystathionin beta synthase (CBS) domain and the carboxy-terminal protein segment. A novel finding was that aldosterone inhibition with spironolactone helped to alleviate hypomagnesemia and symptoms in the proband.