Milk exosomes and a new way of communication between mother and child.

Extracellular vesicles are a heterogeneous group of lipid-bound vesicles released by cells into the extracellular space. EVs are an important mediator of intercellular communications and carry a wide variety of molecules that exert a biological function, such as lipids, nucleic acids, proteins, ions, and adenosine triphosphate (ATP). Extracellular vesicles are classified into microvesicles, exosomes, and apoptotic bodies depending on their biogenesis and size. Exosomes are spherical lipid-bilayer vesicles with a diameter of about 40 to 100 nm. Exosomes originate from intracellular endosomal compartments, while microvesicles originated directly from a cell's plasma membrane and apoptotic bodies originate from cells undergoing apoptosis and are released via outward blebbing and fragmentation of the plasma membrane. Specifically, exosomes have garnered great attention since they display great potential as both biomarkers and carriers of therapeutic molecules.

Exosomal Epigenetics.

Epigenetics is the study of heritable changes in gene expression that occur without changes to the underlying DNA sequence. Epigenetic modifications can include DNA methylation, histone modifications, and non-coding RNAs, among others. These modifications can influence the expression of genes by altering the way DNA is packaged and accessed by transcriptional machinery, thereby affecting cellular function and behavior. Epigenetic modifications can be influenced by a variety of factors, including environmental exposures, lifestyle factors, and aging, whilst abnormal epigenetic modifications have been implicated in a range of diseases, including cancer, neurodegenerative disorders, and cardiovascular disease. The study of epigenetics has the potential to provide new insights into the mechanisms of disease and could lead to the development of new diagnostic and therapeutic strategies. Exosomes can transfer epigenetic information to recipient cells, thereby influencing various physiological and pathological processes, and the identification of specific epigenetic modifications that are associated with a particular disease could lead to the development of targeted therapies that restore normal gene expression patterns. In recent years, the emerging role of exosomal epigenetics in human breast milk, highlighting its significance in infant nutrition and immune development. Milk exosomes are shown to carry epigenetic regulators, including miRNAs and long non-coding RNAs, which can modulate gene expression in recipient cells. These epigenetic modifications mediated by milk exosomal RNAs have implications for the development of the gastrointestinal tract, immune system, and metabolic processes in infants.

SNP and Structural Study of the Notch Superfamily Provides Insights and Novel Pharmacological Targets against the CADASIL Syndrome and Neurodegenerative Diseases.

The evolutionary conserved Notch signaling pathway functions as a mediator of direct cell-cell communication between neighboring cells during development. Notch plays a crucial role in various fundamental biological processes in a wide range of tissues. Accordingly, the aberrant signaling of this pathway underlies multiple genetic pathologies such as developmental syndromes, congenital disorders, neurodegenerative diseases, and cancer. Over the last two decades, significant data have shown that the Notch signaling pathway displays a significant function in the mature brains of vertebrates and invertebrates beyond neuronal development and specification during embryonic development. Neuronal connection, synaptic plasticity, learning, and memory appear to be regulated by this pathway. Specific mutations in human Notch family proteins have been linked to several neurodegenerative diseases including Alzheimer's disease, CADASIL, and ischemic injury. Neurodegenerative diseases are incurable disorders of the central nervous system that cause the progressive degeneration and/or death of brain nerve cells, affecting both mental function and movement (ataxia). There is currently a lot of study being conducted to better understand the molecular mechanisms by which Notch plays an essential role in the mature brain. In this study, an in silico analysis of polymorphisms and mutations in human Notch family members that lead to neurodegenerative diseases was performed in order to investigate the correlations among Notch family proteins and neurodegenerative diseases. Particular emphasis was placed on the study of mutations in the Notch3 protein and the structure analysis of the mutant Notch3 protein that leads to the manifestation of the CADASIL syndrome in order to spot possible conserved mutations and interpret the effect of these mutations in the Notch3 protein structure. Conserved mutations of cysteine residues may be candidate pharmacological targets for the potential therapy of CADASIL syndrome.

Thyroid Diseases and Intestinal Microbiome.

The human microbiome plays an integral role in health. In particular, it is important for the development, differentiation, and maturation of the immune system, 70% of which resides in the intestinal mucosa. Microbiome studies conducted to date have revealed an association between disturbances in the microbiota (dysbiosis) and various pathological disorders, including changes in host immune status. Autoimmune thyroid diseases are one of the most common organ-specific autoimmune disorders, with a worldwide prevalence higher than 5%. The predominant autoimmune thyroid diseases are Hashimoto's thyroiditis and Grave's disease. Several factors, such as genetic and environmental ones, have been studied. In accordance with recent studies, it is assumed that the gut microbiome might play a significant role in triggering autoimmune diseases of the thyroid gland. However, the exact etiology has not yet been elucidated. The present review aims to describe the work carried out so far regarding the role of gut microflora in the pathogenesis of autoimmune thyroid diseases and its involvement in the appearance of benign nodules and papillary thyroid cancer. It appears that future work is needed to elucidate more precisely the mechanism for gut microbiota involvement in the development of autoimmune thyroid diseases.

Review of Disease-Specific microRNAs by Strategically Bridging Genetics and Epigenetics in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most prevalent human malignancies and a global health concern with a poor prognosis despite some therapeutic advances, highlighting the need for a better understanding of its molecular etiology. The genomic landscape of OSCC is well-established and recent research has focused on miRNAs, which regulate gene expression and may be useful non-invasive biomarkers or therapeutic targets. A plethora of findings regarding miRNA expression have been generated, posing challenges for the interpretation and identification of disease-specific molecules. Hence, we opted to identify the most important regulatory miRNAs by bridging genetics and epigenetics, focusing on the key genes implicated in OSCC development. Based on published reports, we have developed custom panels of fifteen major oncogenes and five major tumor suppressor genes. Following a miRNA/target gene interaction analysis and a comprehensive study of the literature, we selected the miRNA molecules which target the majority of these panels that have been reported to be downregulated or upregulated in OSCC, respectively. As a result, miR-34a-5p, miR-155-5p, miR-124-3p, miR-1-3p, and miR-16-5p appeared to be the most OSCC-specific. Their expression patterns, verified targets, and the signaling pathways affected by their dysregulation in OSCC are thoroughly discussed.

A Systematic Review on the Adult Alpha Brainwave Activity After Essential Oil Inhalation.

Aroma extracts from plant species have been utilized since ancient times for a variety of discomforting circumstances. Aromatherapy is a recognized complementary therapeutic treatment performed in various ways such as massage or dermal application, with its main uses involving relaxation, pain relief, and stress management. Several studies have outlined that inhalation of fragrance may influence the brain function since their components can cross the blood-brain barrier and interact with central nervous system receptors. The aim of this review was to systematically present findings regarding alpha brain wave activity reported exclusively by electroencephalography. The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed and Scopus databases were screened for relevant papers, based on specific eligibility criteria. The final step of the process resulted in 13 studies published between 1998 and 2021, using different essential oils. Most of the studies revealed the increase of alpha brainwave activity post-essential oil inhalation. Given the proven positive outcomes of increased alpha wave activity on several domains such as cognitive performance and better mental state, further research on the impact of essential oil inhalation is warranted.

Soft Tissue Ewing Sarcoma Cell Drug Resistance Revisited: A Systems Biology Approach.

Ewing sarcoma is a rare type of cancer that develops in the bones and soft tissues. Drug therapy represents an extensively used modality for the treatment of sarcomas. However, cancer cells tend to develop resistance to antineoplastic agents, thereby posing a major barrier in treatment effectiveness. Thus, there is a need to uncover the molecular mechanisms underlying chemoresistance in sarcomas and, hence, to enhance the anticancer treatment outcome. In this study, a differential gene expression analysis was conducted on high-throughput transcriptomic data of chemoresistant versus chemoresponsive Ewing sarcoma cells. By applying functional enrichment analysis and protein-protein interactions on the differentially expressed genes and their corresponding products, we uncovered genes with a hub role in drug resistance. Granted that non-coding RNA epigenetic regulators play a pivotal role in chemotherapy by targeting genes associated with drug response, we investigated the non-coding RNA molecules that potentially regulate the expression of the detected chemoresistance genes. Of particular importance, some chemoresistance-relevant genes were associated with the autonomic nervous system, suggesting the involvement of the latter in the drug response. The findings of this study could be taken into consideration in the clinical setting for the accurate assessment of drug response in sarcoma patients and the application of tailored therapeutic strategies.

Angiotensinogen, Angiotensin-Converting Enzyme, and Chymase Gene Polymorphisms as Biomarkers for Basal Cell Carcinoma Susceptibility.

INTRODUCTION: The intake of angiotensin-converting enzyme (ACE) inhibitors and specific antagonists of angiotensin II receptors, widely used as antihypertensive drugs, significantly reduces the risk of developing basal cell carcinoma (BCC), highlighting the possible tumorigenic role of angiotensin II (AngII). We present here the investigated genetic association between the development of BCC and functional DNA polymorphisms M235T, I/D, and A1903G in the genes of angiotensinogen (AGT), angiotensin-converting enzyme (ACE), and chymase (CMA1), which mediate AngII production levels. METHODS: DNA samples of 203 unrelated Greeks were studied, including 100 patients with BCC and 103 matched healthy controls. RESULTS: The MT genotype of the AGT-M235T polymorphism was significantly more prevalent in the patient group (78.0%) versus the healthy control group (28.3%; p < 0.001). The DD genotype of the ACE-I/D polymorphism was also increased in BCC patients (72.8%) compared to controls (46.2%; p = 0.001). The heterozygous AG genotype of CMA1-A1903G was significantly more frequent in the BCC group (86%) than in the healthy controls (50.5%; p < 0.001). CONCLUSIONS: The MT, DD, and AG genotypes of the AGT- M235T, ACE-I/D, and CMA1-A1903G polymorphisms, respectively, were significantly increased in frequency within the group of cancer patients compared to the healthy controls. All three genotypes correspond to increased enzyme levels or activity and result in increased levels of AngII; therefore, they may be potentially utilized as reliable biomarkers associated with an individual's increased risk for BCC development.

Clinical and Molecular Genetic Analysis of Cases with Ectodermal Dysplasia.

INTRODUCTION: Ectodermal dysplasias are a group of >200 clinically and congenitally heterogeneous disorders characterized by abnormal development in the ectodermal structures, such as hair, nails, teeth, and sweat glands. We report here the clinical and molecular genetic analysis of five Greek families with different types of ectodermal dysplasia (ED). SUBJECTS: The study involved 15 individuals from 5 Greek families that included 8 ED patients, 5 carriers of recessive X-linked or autosomal ED, and 2 healthy relatives. After genetic counseling, the parents signed an informed consent form before subsequent genetic testing. METHODS: Genomic DNA was isolated from white blood cells of all studied individuals. The search for mutations was realized in patients' DNA samples using next-generation sequencing (NGS) gene panel, whole exome sequencing (WES), chromosomal microarray analysis (CMA), and multiplex ligation-dependent probe amplification (MLPA) technique. RESULTS: The clinical diagnosis of common X-linked recessive hypohidrotic ectodermal dysplasia (HED) was suspected in five male patients with partial anodontia of baby and permanent teeth, hypohidrosis, and thin hair from three families. All HED patients were hemizygous for deletions in the EDA1 gene (Xq13.1): three related patients had a 20 bp deletion, one had a 19 bp deletion, and one had a 180 bp deletion. A female patient had the rare autosomal dominant syndrome of ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC) caused by heterozygous missense mutation in the TP63 gene (3q28) that appeared de novo. Two siblings with hypotrichosis and hypodontia, a female and a male, had two pathogenic mutations in compound heterozygosity in the TSPEAR gene (21q22.3); therefore they presented with ectodermal dysplasia type 14 (ECTD14). CONCLUSION: Clinical and molecular genetic analysis may set an accurate diagnosis of different types of ED. In the reported families, genetic diagnosis and genetic counselling assisted the parents to view their children's condition realistically and to cooperate with the specialists who will contribute to the best possible treatment for their children.

Human Breast Milk Omics and Neurodevelopment.

Breast milk is the ideal food for the premature and mature babies and has undoubtedly immediate and ultimate benefits. Among other things, it protects against infections, reduces the risk of necrotizing enterocolitis and retinopathy of the premature babies, improves neurodevelopmental outcome, and reduces the risk of obesity and metabolic syndrome later in life. In the present study, breast milk will be studied with all the available omics technologies. More specifically, functional genomics, comparative genomics, transcriptomics, sequencing, proteomics, and metabolomics will be performed. The above results and this multidimensional information will be coordinated under the framework of a holistic approach of systems biology and bioinformatic analysis. Important IncRNAs and protein molecules will be validated as candidate biomarkers in exosomes of a larger group of breast milk and blood/serum samples. Validated ncRNAs/proteins will be analyzed in exudates of breast milk and bovine, goat, and sheep milk to explore new ways to improve milk synthesis. Expression of ncRNAs, unlike mRNAs, is a direct indicator of their functional presence. The information to be generated in this study will be analyzed by mining and data combining techniques and algorithms. After defining breast milk molecular fingerprinting, an attempt will be made to enhance the commercial product. The benefits of breast milk are attributed to its various components, including nutrients, hormones, growth factors, immune cells, antibodies, cytokines, antimicrobial peptides, and extracellular vesicles.

Characteristics of Café-au-lait Macules and their Association with the Neurofibromatosis type I Genotype in a Cohort of Greek Children.

Cafe-au-lait macules are the most distinctive clinical finding in neurofibromatosis type I. The aim of this prospective study of Greek children diagnosed with neurofibromatosis type I was to describe the dermatological phenotype and to analyse the characteristics of cafe-au-lait macules and their association with genotype. Pigment intensity and melatonin content of cafe-au-lait macules were measured with a narrowband spectrophotometer. A total of 63 children aged 6 months to 16 years old were studied. Mean melanin content varied, both among patients, and within each patient (p < 0.001). Females had a higher number of cafe-au-lait macules than did males (p = 0.025), and the melanin content of cafe-au-lait macules was lower in females than males (p < 0.001). Patients with protein-truncating variants in the neurofibromatosis type I gene had higher melanin content of cafe-au-lait macules than other types of genetic variants t (55) = 2.196, p = 0.032. Plexiform neurofibromas were also detected in the majority of patients with protein- truncating variants, while juvenile xanthogranulomas were detected equally in patients with protein-truncating and non-protein-truncating variants. In conclusion, cafe-au-lait macules with high melatonin content are associated with patients carrying non-protein-truncating variants. Therefore, measurement of cafe-au-lait macule pigment intensity might provide useful information for initial assessment of patients with neurofibromatosis type I and the severity of their future phenotype.

Molecular Modeling Analysis Provides Genotype-Phenotype Correlation Insights in a Patient with Ankyloblepharon-Ectodermal Dysplasia-Clefting Syndrome.

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare autosomal dominant disorder. AEC is caused by mutations in the TP63 gene that encodes the tumor suppressor p63 protein, itself involved in the regulation of epidermal proliferation, development, and differentiation. We present here a typical AEC case of a four-year-old girl with extensive skin erosions and erythroderma of the scalp and the trunk, and to a lesser extent of the limbs, nail dystrophy on the fingers and toes, xerophthalmia, a high-arched palate, oligodontia, and hypohidrosis. Mutation analysis of the TP63 gene detected a de novo missense mutation in exon 14 (c.1799G>T; p.Gly600Val). We discuss the phenotype-genotype correlation by presenting the clinical features of AEC in the patient, and the effect of the detected mutation in p63 structure and function using protein structural modeling, in view of similar cases in the literature. We performed a molecular modeling study in order to link the effect on the protein structure level of the missense mutation G600V. We noted that the introduction of the bulkier Valine residue in place of the slim Glycine residue caused a significantly altered 3D conformational arrangement of that protein region, pushing away the adjacent antiparallel α helix. We propose that the introduced locally altered structure of the G600V mutant p63 has a significant functional effect on specific protein-protein interactions, thus affecting the clinical phenotype.

Stress and Well-Being of Greek Primary School Educators: A Cross-Sectional Study.

The teaching profession has always been challenging, while for various reasons the magnitude of observed stress in teachers has been continually growing over time. This study was conducted to demonstrate the relevance of stress in this professional group and to generate evidence for the benefit of primary school teachers and, indirectly, their pupils. To this end, we examined a large number of school teachers in a descriptive cross-sectional study. The survey comprised 786 primary school instructors aged 21 to 65 years, 646 women (82.2%) and 140 males (17.8%), and was performed from March to October 2022. Participants were asked about their gender, age, marital status, place of domicile, satisfaction with their income, whether their income met their needs, number of children, whether they cared for a person with a disability, work experience, alcohol use, eating patterns, and their height and weight for computation of their Body Mass Index (BMI). The survey included the Teacher Subjective Well-being Questionnaire (TSWQ), the Perceived Stress Scale (PSS), the Healthy Lifestyle and Personal Control Questionnaire (HLPCQ), and the Pittsburgh Sleep Quality Index (PSQI). The results showed that there were significant differences between the two sexes in age, marital status, work experience, smoking, alcohol use, and eating breakfast. Furthermore, there were significant differences between the two sexes in BMI, PSS Total, Dietary Health Choice, Harm Avoidance and Total HLPCQ. The variance of PSS Total was predicted by Sex, Teacher Efficacy, Total PSQI, Dietary Health Choice, organized physical exercise, social support and mental control, and Total HLPCQ. Between teacher efficacy, school connectedness, teacher well-being, organized physical exercise, social support and mental control, Total HLPCQ and PSS Total, the correlation coefficients were negative and significant at the <0.05 level. Between Total PSQI and PSS Total, the correlation coefficient was positive and significant at the <0.05 level. Between teacher efficacy, school connectedness and teacher well-being, organized physical exercise, social support and mental control, Total HLPCQ and Total PSQI, the correlation coefficients were negative and significant at the <0.05 level. In summary, we demonstrated that Greek primary school teachers experience significant stress, which is intertwined with their way of life, and reflected in significant decreases in their sense of well-being, quality of sleep, and overall life satisfaction, as well as in their standards of teaching.

Cardiovascular Magnetic Resonance Imaging Patterns in Rare Cardiovascular Diseases.

Rare cardiovascular diseases (RCDs) have low incidence but major clinical impact. RCDs' classification includes Class I-systemic circulation, Class II-pulmonary circulation, Class III-cardiomyopathies, Class IV-congenital cardiovascular diseases (CVD), Class V-cardiac tumors and CVD in malignancy, Class VI-cardiac arrhythmogenic disorders, Class VII-CVD in pregnancy, Class VIII-unclassified rare CVD. Cardiovascular Magnetic Resonance (CMR) is useful in the diagnosis/management of RCDs, as it performs angiography, function, perfusion, and tissue characterization in the same examination. Edema expressed as a high signal in STIRT2 or increased T2 mapping is common in acute/active inflammatory states. Diffuse subendocardial fibrosis, expressed as diffuse late gadolinium enhancement (LGE), is characteristic of microvascular disease as in systemic sclerosis, small vessel vasculitis, cardiac amyloidosis, and metabolic disorders. Replacement fibrosis, expressed as LGE, in the inferolateral wall of the left ventricle (LV) is typical of neuromuscular disorders. Patchy LGE with concurrent edema is typical of myocarditis, irrespective of the cause. Cardiac hypertrophy is characteristic in hypertrophic cardiomyopathy (HCM), cardiac amyloidosis (CA) and Anderson-Fabry Disease (AFD), but LGE is located in the IVS, subendocardium and lateral wall in HCM, CA and AFD, respectively. Native T1 mapping is increased in HCM and CA and reduced in AFD. Magnetic resonance angiography provides information on aortopathies, such as Marfan, Turner syndrome and Takayasu vasculitis. LGE in the right ventricle is the typical finding of ARVC, but it may involve LV, leading to the diagnosis of arrhythmogenic cardiomyopathy. Tissue changes in RCDs may be detected only through parametric imaging indices.

Long non­coding RNAs and microRNAs as regulators of stress in cancer (Review).

Resistance to stress is a feature of cancer cells. Cellular stress includes oxidative, metabolic and genotoxic stress conditions, which under normal conditions lead to cell death. However, in contrast to normal cells, cancer cells overcome the checkpoints that normally restrict growth, and are able to resist cellular stress and subsequent cell death through a variety of mechanisms, which include several non­coding RNAs (ncRNAs). Within this context, long ncRNAs (lncRNAs) and microRNAs (miRNAs/miRs) are the main categories of ncRNAs that have been shown in the literature to function as regulators of stress resistance pathways in cancer. miRNAs play a key role in the majority of biological pathways, as they regulate the expression of hundreds of target genes, including genes involved in stress response and cell death, oncogenes, or tumor suppressor genes, by inhibiting protein translation or promoting the degradation of mRNAs. Respectively, lncRNAs are epigenetic regulators, which are also involved in cancer progression, stress response and metabolic pathways by promoting or inhibiting the transcription, splicing, translation and modulation of protein function. Thus, the present review summarizes recent knowledge related to the role of these molecules in the cancer response to stress, highlighting the ability of these non­coding molecules to be effective drug targets and biomarkers in cancer treatment.

Protracted stress-induced hypocortisolemia may account for the clinical and immune manifestations of Long COVID.

About one out of eight people to convalesce from COVID-19 suffer from the so called Long COVID, a syndrome of non-specific symptoms with unclear pathogenesis. In a recent study published in Cell Long COVID participants reporting respiratory symptoms had low cortisol levels. In an as yet unpublished analysis from Yale University low plasma cortisol levels discriminated Long COVID from asymptomatic convalescent or healthy non-infected controls. Although various immune perturbations were present in Long COVID, low levels of cortisol were prominent and strikingly, depression and anxiety were increased. It has become clear that Long COVID features may be similar to those described in myalgic encephalomyelitis/chronic fatigue syndrome, post-SARS sickness syndrome, and various chronic stress syndromes which have been linked to hypocortisolemia. Notably, lack of response of the hypothalamic-pituitary-adrenal axis to hypocortisolemia shows a suppressed axis in Long COVID. We suggest that the inability of hypothalamic-pituitary-adrenal axis to recover after the acute illness, perhaps due to protracted stress in predisposed individuals, may represent the pathogenetic basis of the Long COVID-associated clinical and immunological manifestations.

Metabolic effects of truncal vagotomy when combined with bariatric-metabolic surgery.

Bariatric-metabolic surgery (BMS) in patients with obesity frequently leads to remission of concurrent type 2 diabetes mellitus (T2DM), even before body weight loss takes place. This is probably based on the correction of a dysmetabolic cycle in the gastrointestinal physiology of T2DM that includes increased vagus-dependent exocrine pancreatic secretion (EPS) and, hence, amplified digestion and nutrient absorption. The resultant chronic exposure of tissues to high plasma levels of glucose, fatty acids and amino acids causes tissue resistance to the actions of insulin and, at a later stage, ß-cell dysfunction and reduction of insulin release. We hypothesize that the addition of a surgical truncal vagotomy (TV) may improve and solidify the beneficial results of BMS on T2DM by stably decreasing EPS, - hence reducing the digestion and absorption of nutrients -, and increasing incretin secretion as a result of increased delivery of unabsorbed nutrients to the distal intestine. This hypothesis is supported by surgical data from gastrointestinal malignancies and peptic ulcer operations that include TV, as well as by vagal blockade studies. We suggest that TV may result in a stable reduction of EPS, and that its combination with the appropriate type of BΜS, may enhance and sustain the salutary effects of the latter on T2DM.

An In Vitro Study of Saffron Carotenoids: The Effect of Crocin Extracts and Dimethylcrocetin on Cancer Cell Lines.

Crocus sativus L. has various pharmacological properties, known for over 3600 years. These properties are attributed mainly to biologically active substances, which belong to the terpenoid group and include crocins, picrocrocin and safranal. The aim of the current work was to examine the effects of crocins (CRCs) and their methyl ester derivate dimethylcrocetin (DMCRT) on glioblastoma and rhabdomyosarcoma cell lines, in terms of cytotoxicity and gene expression, implicated in proapoptotic and cell survival pathways. Cell cytotoxicity was assessed with Alamar Blue fluorescence assay after treatment with saffron carotenoids for 24, 48 and 72 h and concentrations ranging from 22.85 to 0.18 mg/mL for CRCs and 11.43 to 0.09 mg/mL for DMCRT. In addition, BAX, BID, BCL2, MYCN, SOD1, and GSTM1 gene expression was studied by qRT-PCR analysis. Both compounds demonstrated cytotoxic effects against glioblastoma and rhabdomyosarcoma cell lines, in a dose- and time-dependent manner. They induced apoptosis, via BAX and BID upregulation, MYCN and BCL-2, SOD1, GSTM1 downregulation. The current research denotes the possible anticancer properties of saffron carotenoids, which are considered safe phytochemicals, already tested in clinical trials for their health promoting properties.

Integrated Deadenylase Genetic Association Network and Transcriptome Analysis in Thoracic Carcinomas.

The poly(A) tail at the 3' end of mRNAs determines their stability, translational efficiency, and fate. The shortening of the poly(A) tail, and its efficient removal, triggers the degradation of mRNAs, thus, regulating gene expression. The process is catalyzed by a family of enzymes, known as deadenylases. As the dysregulation of gene expression is a hallmark of cancer, understanding the role of deadenylases has gained additional interest. Herein, the genetic association network shows that CNOT6 and CNOT7 are the most prevalent and most interconnected nodes in the equilibrated diagram. Subsequent silencing and transcriptomic analysis identifies transcripts possibly regulated by specific deadenylases. Furthermore, several gene ontologies are enriched by common deregulated genes. Given the potential concerted action and overlapping functions of deadenylases, we examined the effect of silencing a deadenylase on the remaining ones. Our results suggest that specific deadenylases target unique subsets of mRNAs, whilst at the same time, multiple deadenylases may affect the same mRNAs with overlapping functions.

Molecular fusion events in carcinogenic organisms: a bioinformatics study for the detection of fused proteins between viruses, bacteria and eukaryotes.

Molecular fusion events have a prominent role in the initial steps of carcinogenesis. In this study, a bioinformatics analysis was performed between four organisms that are known to induce cancer development in humans: two viruses, Human Herpesvirus 4, and Human T-cell leukaemia virus, one bacterium, Helicobacter Pylori, and one trematode, Schistosoma mansoni. The annotated proteomes from these organisms were analysed using the SAFE software to identify protein fusion events, which may provide insight into protein function similarities and possible merging events during the course of evolution. Based on the results, five fused proteins with very similar functions were detected, whereas proteins with different functions that might act in the same molecular complex or biochemical pathway were not found. Thus, this study analysed the above four well-known cancer-related organisms with de novo bioinformatics programs and provided useful information on protein fusion events, hopefully leading to deeper understanding of carcinogenenesis.