Bioetics Issues of Artificial Placenta and Artificial Womb Technology.

Abstract: The worldwide infertility crisis and the increase in mortality and morbidity among infants, due to preterm births and associated complications, have stimulated research into artificial placenta (AP) and artificial womb (AW) technology as novel solutions. These technologies mimic the natural environment provided in the mother's womb, using chambers that ensure the supply of nutrients to the fetus and disposal of waste substances through an appropriate mechanism. This review aims to highlight the background of AP and AW technologies, revisit their historical development and proposed applications, and discuss challenges and bioethical and moral issues. Further research is required to investigate any negative effects of these new technologies, and ethical concerns pertaining to the structure and operation of this newly developed technology must be addressed and resolved prior to its introduction to the public sphere.

In Memory of Professor Derek Pheby.

Abstract: Professor Derek Pheby's passing in November 2022 marked a profound loss for the scientific community. Professor Derek Pheby, a stalwart figure in the fields of autoimmune diseases and bioethics, was known for his dedication to scientific research and patients' support, particularly for those affected by paraneoplastic autoimmune syndromes. Professor Pheby made significant contributions to research, especially about Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). His leadership of the ME Biobank and scientific coordination of EUROMENE demonstrated his commitment to pushing boundaries and fostering international collaborations. Professor Pheby's scientific work addressed various aspects of ME/CFS, from physician education to patient needs, the development of a post-mortem tissue bank, and effective treatments. Beyond his medical career, Professor Pheby was a crucial member of the Independent Ethics Committee of MAGI, he was a poet, humanitarian, and advocate for child protection. His generosity and boundless spirit left an enduring legacy, fostering innovative research in the pursuit of combating autoimmune diseases.

X-linked genodermatoses from diagnosis to tailored therapy.

Background: Genodermatoses are rare heterogeneous genetic skin diseases with multiorgan involvement. They severely impair an individual's well-being and can also lead to early death. Methods: During the progress of this review, we have implemented a targeted research approach, diligently choosing the most relevant and exemplary articles within the subject matter. Our method entailed a systematic exploration of the scientific literature to ensure a compre-hensive and accurate compilation of the available sources. Results: Among genodermatoses, X-linked ones are of particular importance and should always be considered when pediatric males are affected. Regardless of other syndromic forms without prevalence of skin symptoms, X-linked genodermatoses can be classified in three main groups: keratinization defects, pigmentation defects, and inflammatory skin diseases. Typical examples are dyskeratosis congenita, keratosis follicularis spinulosa decalvans, hypohidrotic ectodermal dysplasia, chondrodysplasia punctata, hypohidrotic ectodermal dysplasia, incontinentia pigmenti, chronic granulomatous disease, CHILD syndrome and ichthyosis. In this field, genetic diagnosis of the specific disease is important, also considering that numerous clinical trials of orphan drugs and genetic therapies are being proposed for these rare genetic diseases. Conclusions: Thus, this chapter starts from clinical to molecular testing and ends with a review of all clinical trials on orphan drugs and gene therapy for genodermatoses.

Non-Invasive Screening Test Paradox in a Case Born with Mixed Gonadal Dysgenesis (45,X/46,Xy).

Noninvasive prenatal testing (NIPT) is commonly used to screen for fetal trisomy 13, 18, and 21 and often for sex chromosomal aneuploidies (SCAs). Although the testing is also used for sex chromosomal aneuploidies, it is not as efficient as it is for common trisomies. In this particular study, we present a case for whom the NIPT diagnosis was originally 45,X and who was diagnosed with mixed gonadal dysgenesis 45,X/46,XY after birth. A 38-year-old [G3P3] pregnant woman underwent NIPT at 15 weeks' gestation and was found to be at probable risk for 45,X. Because cordocentesis is an invasive procedure, the pregnant woman did not want to undergo cordocentesis. Consequently, postnatal cytogenetic analysis was performed and the baby's karyotype was shown to be 45,X/46,X,+mar?. No numerical and/or structural anomalies were observed in the karyotypes of parents and siblings. Based on the microarray analysis of the analyzed sample, one copy of the X chromosome was detected in all cells and the presence of one copy of the Y chromosome was detected in a ~40% mosaic state: arr(X) x1,(Y)x1[0.4]. SRY gene duplication on Y chromosome was confirmed by fluorescence in situ hybridization (FISH) and microarray analysis. The patient's clinical examination showed ambiguous genitalia (clitoromegaly) and dysmorphic facial features. The baby underwent surgery for aortic coarctation. The results were consistent with a genetic diagnosis of 45,X/46,XY mixed gonadal dysgenesis. Genetic counselling was offered to the family. In conclusion, NIPT still has potential limitations in correctly identifying sex chromosomes and mosaicism that may mislead clinicians and families.

In vitro and clinical studies on the efficacy of α-cyclodextrin and hydroxytyrosol against SARS-CoV-2 infection.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new coronavirus responsible for the current pandemic of coronavirus disease 2019 (COVID-19). This virus attacks cells of the airway epithelium by binding transmembrane angiotensin-converting enzyme 2 (ACE2). Hydroxytyrosol has anti-viral properties. Alpha-cyclodextrin can deplete sphingolipids and phospholipids from cell membranes. The aim of the present experimental study was to evaluate the efficacy of α-cyclodextrin and hydroxytyrosol in improving defenses against SARS-CoV-2 infection in in vitro cell models and humans. PATIENTS AND METHODS: For in vitro experiments on Vero E6 cells, RNA for RT-qPCR analysis was extracted from Caco2 and human fibroblast cell lines. For study in humans, the treatment group consisted of 149 healthy volunteers in Northern Cyprus, considered at higher risk of SARS-CoV-2 infection than the general population. The volunteers used nasal spray containing α-cyclodextrin and hydroxytyrosol for 4 weeks. The control group consisted of 76 healthy volunteers who did not use the spray. RESULTS: RT-qPCR experiments on targeted genes involved in endocytosis showed a reduction in gene expression, whereas cytotoxicity and cytoprotective tests showed that the compounds exerted a protective effect against SARS-CoV-2 infection at non-cytotoxic concentrations. None of the volunteers became positive to SARS-CoV-2 RT-qPCR assay during the 30 days of treatment. CONCLUSIONS: Treatment with α-cyclodextrin and hydroxytyrosol nasal spray improved defenses against SARS-CoV-2 infection and reduced synthesis of viral particles.

Scoping review on the role and interactions of hydroxytyrosol and alpha-cyclodextrin in lipid-raft-mediated endocytosis of SARS-CoV-2 and bioinformatic molecular docking studies.

OBJECTIVE: The aim of the study was to show the effect that two naturally occurring compounds, a cyclodextrin and hydroxytyrosol, can have on the entry of SARS-CoV-2 into human cells. MATERIALS AND METHODS: The PubMed database was searched to retrieve studies published from 2000 to 2020, satisfying the inclusion criteria. The search keywords were: SARS-CoV, SARS-CoV-2, coronavirus, lipid raft, endocytosis, hydroxytyrosol, cyclodextrin. Modeling of alpha-cyclodextrin and hydroxytyrosol were done using UCSF Chimera 1.14. RESULTS: The search results indicated that cyclodextrins can reduce the efficiency of viral endocytosis and that hydroxytyrosol has antiviral properties. Bioinformatic docking studies showed that alpha-cyclodextrin and hydroxytyrosol, alone or in combination, interact with the viral spike protein and its host cell receptor ACE2, thereby potentially influencing the endocytosis process. CONCLUSIONS: Hydroxytyrosol and alpha-cyclodextrin can be useful against the spread of SARS-CoV-2.

Dual Effect of the GHRL Gene Variant in the Molecular Pathogenesis of Obesity.

Obesity is as a global health problem due to its interaction with complex chronic disorders such as cardiovascular disorders, type 2 diabetes mellitus (T2DM) and cancer. Despite the fact that pathogenesis of obesity is not yet clearly understood, it is associated with a combination of psychological, environmental and various genetic factors. Here, employing a case-control design, we aimed to examine the effects of the GHRL c.152C>T (p.Arg51Gln) (rs34911341) and c.214G>T (p.Leu72Met) (rs696217) markers on susceptibility to obesity in a Turkish-Cypriot population, as well as to evaluate whether these markers affect biochemical parameters and show their putative functional consequences. This study involved 211 Turkish-Cypriot subjects (106 obese and 95 non obese). Genotyping for the GHRL gene polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Our results indicate that the GHRL Leu72Met polymorphism was found to be significantly higher in obese patients, with respect to genotypic (p = 0.0012) and allelic (p = 0.0005) frequencies. Strikingly, the rs696217 GT genotype (heterozygous) had significantly lower serum high-density lipoprotein cholesterol (HDL-C) (p = 0.015) than GG (wild type) genotypes. Overall, Leu72Met susceptibility variant may be considered as risk and crucial marker for both obesity and cholesterol metabolism in the community of Turkish-Cypriots. Thus, the dual effect of the GHRL gene Leu72Met variant may be used for clinical diagnosis.

Mutation Status and Immunohistochemical Correlation of EGFR Mutations in Gastrointestinal Stromal Tumors.

Being one of the leading causes of cancer deaths worldwide and their resistance to conventional treatment methods, made gastrointestinal stromal tumors (GISTs) one of the hot topics in medical research areas in the past decade. To investigate molecular alterations underlying the tumor is of great importance to be able to develop new, targeted treatment options. In this study, GIST samples obtained from 40 Turkish patients were analyzed for actionable epidermal growth factor receptor (EGFR) mutations that are related to treatment regimes in non small cell lung cancer (NSCLC) to understand whether EGFR expression is altered in GISTs. Established alterations in EGFR can make the use of tyrosine kinase inhibitors possible, which are currently used in cancer therapy, especially in NSCLC. Our results indicated that EGFR mutations are rare in GISTs. Further research is needed to sequence whole coding regions of the gene to investigate new actionable mutations in EGFR in an increased sample size.

First direct human-to-cat transmission of the SARS-CoV-2 B.1.1.7 variant.

A highly transmissible severe acute respiratory coronavirus 2 (SARS-CoV-2) caused the coronavirus diseases 2019 (COVID-19) pandemic, which resulted the highest morbidity and mortality rates among SARS-CoV and MERS-CoV. SARS-CoV-2 B.1.1.7 variant indicated the higher transmission among human-to-human and increasing hospitalisation. SARS-CoV-2 infection was observed in domestic animals showing human-to-pet transmission. In the current study, we report the first direct known human-to-cat transmission of the SARS-CoV-2 B.1.1.7 variant within the same family. Previous findings showed that companion animals can get infected by COVID-19 patients after 3-6 weeks; however, according to our molecular findings, the cat was infected by the viral variant at the same period. Moreover, B.1.1.7 infection caused and developed several clinical symptoms including cardiac and ocular abnormalities. Overall, our findings determined the first direct and high transmission ability of the B.1.1.7 variant from COVID-19 affected family members to cat. This result showed that the SARS-CoV-2 B.1.1.7 variant could have the highest transition capacity from human to domestic cat as shown for human-to-human. The governmental or worldwide policies should consider more detailed against the war with COVID-19 pandemic.

Investigation of KCNQ1 polymorphisms as biomarkers for cardiovascular diseases in the Turkish Cypriots for establishing preventative medical measures.

Potassium channels are important in transmitting electrical signals through potassium ions transport. These potassium channels are made from signals encoded by KCNQ1 gene. KCNQ1 polymorphisms were associated with many diseases, including many metabolic and cardiovascular diseases and therefore they can be employed as biomarkers. In this study we aimed to investigate KCNQ1 polymorphisms in the Turkish Cypriot population to reveal the allele frequencies specific for this population and use these polymorphisms as biomarkers to develop preventative medical measures. The genotypes of KCNQ1 polymorphisms (rs231361, rs231359, rs151290, rs2283228, rs2237895, rs2237896) were investigated for the first time in Turkish Cypriot population. The correlation between genotypes of these polymorphisms and plasma lipid levels in this population was also explored. The results of this study showed that there was significant differences of the allele frequencies of between rs2283228 allele of C and rs2237896 (P > 0.05) in Turkish Cypriot population. There was no association between the genotypes of the six polymorphisms and the lipid metabolism. This study is the first genetic epidemiology study that investigated the allelic frequencies of KCNQ1 polymorphisms associated with metabolic syndromes as well as cardiovascular diseases. This study proves to be crucial since the etiologic determinants and molecular pathology of cardiovascular diseases have not yet clearly understood. This study showed that genome wide association studies should be designed for preventative medicine in the Turkish Cypriot population.

Investigation of potential biomarkers for thrombosis related diseases in Turkish Cypriot population.

Genetic and environmental factors are involved in development of many diseases. The allelic frequencies may differ in different populations and in different ethnic groups. The aim of this study was to investigate the genotypes of MTHFR and factor VII polymorphisms and to identify biomarkers for thrombosis related diseases in Turkish Cypriot population. The lipid profiles and genotypes of MTHFR polymorphisms (rs1801133, rs1801131) and factor VII (rs6046) genes were investigated for the first time in the Turkish Cypriot population. The heterozygosity for MTHFR (rs1801133, rs1801131) and FVII (rs6046) polymorphisms is high in Turkish Cypriot population. The heterozygosity for MTHFR C677T was 38%, MTHFR A1298C was 40% and factor VII G353A was 37%, respectively. Allelic frequencies between males and females were similar. There were no correlations between the genotypes of polymorphisms and the lipid profiles. This study is the first genetic epidemiology study that investigated the allelic frequencies of MTHFR and FVII polymorphisms associated with metabolic syndromes. This study proves to be a crucial analysis in order to use these polymorphisms as a predictor of disease development in the Turkish Cypriot community.