Distinct miRNA Signatures and Networks Discern Fetal from Adult Erythroid Differentiation and Primary from Immortalized Erythroid Cells.

MicroRNAs (miRNAs) are small non-coding RNAs crucial for post-transcriptional and translational regulation of cellular and developmental pathways. The study of miRNAs in erythropoiesis elucidates underlying regulatory mechanisms and facilitates related diagnostic and therapy development. Here, we used DNA Nanoball (DNB) small RNA sequencing to comprehensively characterize miRNAs in human erythroid cell cultures.

Dysbiosis and Enhanced Beta-Defensin Production in Hair Follicles of Patients with Lichen Planopilaris and Frontal Fibrosing Alopecia.

Despite their distinct clinical manifestation, frontal fibrosing alopecia (FFA) and lichen planopilaris (LPP) display similar histopathologic features. Aberrant innate immune responses to endogenous or exogenous triggers have been discussed as factors that could drive inflammatory cascades and the collapse of the stem cell niche. In this exploratory study, we investigate the bacterial composition of scalp skin and plucked hair follicles (HF) of patients with FFA, LPP and alopecia areata circumscripta (AAc), as well as healthy individuals, in relation to cellular infiltrates and the expression of defense mediators.

Laboratory-Generated Urine Toxicology Interpretations: A Mixed Methods Study.

Background: Clinicians frequently order urine drug testing (UDT) for patients on chronic opioid therapy (COT), yet often have difficulty interpreting test results accurately.

Objectives: To evaluate the implementation and effectiveness of a laboratory-generated urine toxicology interpretation service for clinicians prescribing COT.

Study Design: Type II hybrid-convergent mixed methods design (implementation) and pre-post prospective cohort study with matched controls (effectiveness).

Implementation of multigene panel NGS diagnosis in the national primary ciliary dyskinesia cohort of Cyprus: An island with a high disease prevalence.

We aimed to determine a genetic diagnosis in the national primary ciliary dyskinesia (PCD) cohort of Cyprus, an island with a high disease prevalence. We used targeted next-generation sequencing (NGS) of 39 PCD genes in 48 patients of Greek-Cypriot and other ancestries. We achieved a molecular diagnosis in 74% of the unrelated families tested.

AAV9-mediated Schwann cell-targeted gene therapy rescues a model of demyelinating neuropathy.

Mutations in the GJB1 gene, encoding the gap junction (GJ) protein connexin32 (Cx32), cause X-linked Charcot-Marie-Tooth disease (CMT1X), an inherited demyelinating neuropathy. We developed a gene therapy approach for CMT1X using an AAV9 vector to deliver the GJB1/Cx32 gene under the myelin protein zero (Mpz) promoter for targeted expression in Schwann cells. Lumbar intrathecal injection of the AAV9-Mpz.

Toxicity Profiling of Biosurfactants Produced by Novel Marine Bacterial Strains.

Surface active agents (SAAs), currently used in modern industry, are synthetic chemicals produced from non-renewable sources, with potential toxic impacts on humans and the environment. Thus, there is an increased interest for the identification and utilization of natural derived SAAs. As such, the marine environment is considered a promising source of biosurfactants with low toxicity, environmental compatibility, and biodegradation compared to their synthetic counterparts.

An Evaluation of the Anti-Carcinogenic Response of Major Isothiocyanates in Non-Metastatic and Metastatic Melanoma Cells.

Malignant melanoma is one of the most deadly types of solid cancers, a property mainly attributed to its highly aggressive metastatic form. On the other hand, different classes of isothiocyanates, a class of phytochemicals, present in cruciferous vegetables have been characterized by considerable anti-cancer activity in both in vitro and in vivo experimental models. In the current study, we investigated the anti-cancer response of five isothiocyanates in an in vitro model of melanoma consisting of non-metastatic (A375, B16F-10) and metastatic (VMM1, Hs294T) malignant melanoma as well as non-melanoma epidermoid carcinoma (A431) and non-tumorigenic melanocyte-neighboring keratinocyte (HaCaT) cells.

An Early Stage Researcher's Primer on Systems Medicine Terminology.

Systems Medicine is a novel approach to medicine, that is, an interdisciplinary field that considers the human body as a system, composed of multiple parts and of complex relationships at multiple levels, and further integrated into an environment. Exploring Systems Medicine implies understanding and combining concepts coming from diametral different fields, including medicine, biology, statistics, modeling and simulation, and data science. Such heterogeneity leads to semantic issues, which may slow down implementation and fruitful interaction between these highly diverse fields.

A novel methylated analogue of L-Mimosine exerts its therapeutic potency through ROS production and ceramide-induced apoptosis in malignant melanoma.

Melanoma is an aggressive and highly metastatic type of skin cancer where the design of new therapies is of utmost importance for the clinical management of the disease. Thus, we have aimed to investigate the mode of action by which a novel methylated analogue of L-Mimosine (e.g.

Novel Variant Associated With Oculo-Dento-Digital Dysplasia Syndrome: Clinical Phenotype and Cellular Mechanisms.

Oculodentodigital dysplasia syndrome is associated with numerous pathogenic variants in , the gene encoding connexin43 gap junction protein. A novel in-frame deletion (p.Lys134del) was found in our clinic.

Greek Sage Exhibits Neuroprotective Activity against Amyloid Beta-Induced Toxicity.

Alzheimer's disease (AD) is the most common neurodegenerative disease, affecting the elderly at a high incidence. AD is of unknown etiology and currently, no cure is available. Present medication is restricted to treating symptoms; thus, a need exists for the development of effective remedies.

Generalized linear models provide a measure of virulence for specific mutations in SARS-CoV-2 strains.

This study aims to highlight SARS-COV-2 mutations which are associated with increased or decreased viral virulence. We utilize genetic data from all strains available from GISAID and countries' regional information, such as deaths and cases per million, as well as COVID-19-related public health austerity measure response times. Initial indications of selective advantage of specific mutations can be obtained from calculating their frequencies across viral strains.

Muscle-derived exosomes encapsulate myomiRs and are involved in local skeletal muscle tissue communication.

Exosomes are extracellular vesicles that are released from most cell types encapsulating specific molecular cargo. Exosomes serve as mediators of cell-to-cell and tissue-to-tissue communications under normal and pathological conditions. It has been shown that exosomes carrying muscle-specific miRNAs, myomiRs, are secreted from skeletal muscle cells in vitro and are elevated in the blood of muscle disease patients.

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Background: Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking.

Methods: We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes.

Aldehyde Dehydrogenase 1B1 Is Associated with Altered Cell Morphology, Proliferation, Migration and Chemosensitivity in Human Colorectal Adenocarcinoma Cells.

Aldehyde dehydrogenases (ALDHs) are NAD(P)-dependent enzymes that catalyze the oxidation of endogenous and exogenous aldehydes to their corresponding carboxylic acids. ALDHs participate in a variety of cellular mechanisms, such as metabolism, cell proliferation and apoptosis, as well as differentiation and stemness. Over the last few years, ALDHs have emerged as cancer stem cell markers in a wide spectrum of solid tumors and hematological malignancies.

Genetic mechanisms of peripheral nerve disease.

Peripheral neuropathies of genetic etiology are a very diverse group of disorders manifesting either as non-syndromic inherited neuropathies without significant manifestations outside the peripheral nervous system, or as part of a systemic or syndromic genetic disorder. The former and most frequent group is collectively known as Charcot-Marie-Tooth disease (CMT), with prevalence as high as 1:2,500 world-wide, and has proven to be genetically highly heterogeneous. More than 100 different genes have been identified so far to cause various CMT forms, following all possible inheritance patterns.

A Systems Bioinformatics Approach to Interconnect Biological Pathways.

Signal transduction tasks as well as other complex biological processes involve many different changes in groups of genes, proteins, and metabolites linked together in chains or networks called pathways or networks of pathways. In a classical functional analysis, the biomolecules found to play a role in the biological status under investigation are members of a group of pathways that are not necessarily interconnected. However, interconnectivity is a critical factor for functionality.

NGS Panel Testing of Triple-Negative Breast Cancer Patients in Cyprus: A Study of -Negative Cases.

In Cyprus, approximately 9% of triple-negative (estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2-negative) breast cancer (TNBC) patients are positive for germline pathogenic variants (PVs) in . However, the contribution of other genes has not yet been determined. To this end, we aimed to investigate the prevalence of germline PVs in -negative TNBC patients in Cyprus, unselected for family history of cancer or age of diagnosis.

Altered Expression of Glial Gap Junction Proteins Cx43, Cx30, and Cx47 in the 5XFAD Model of Alzheimer's Disease.

Glial gap junction proteins, called connexins (Cxs), form gap junctions in the central nervous system (CNS) to allow the bidirectional cytosolic exchange of molecules between adjacent cells. Their involvement in inheritable diseases and the use of experimental animal models that closely mimic such diseases revealed the critical role of glial GJs in myelination and homeostasis. Cxs are also implicated in acquired demyelinating disorders, such as Multiple Sclerosis (MS) and Alzheimer's disease (AD).

Repurposing denosumab in breast cancer beyond prevention of skeletal related events: Could nonclinical data be translated into clinical practice?

Introduction: Denosumab is a human monoclonal antibody inhibiting the receptor activator of nuclear factor kappa-B ligand (RANKL). Initially approved as antiosteοporotic agent, denosumab is being currently pursued as a candidate for drug repurposing in oncology, especially breast cancer.

Areas Covered: The present review provides an overview of the therapeutic potential of denosumab in breast cancer beyond prevention of skeletal-related events (SREs), with focus on prevention of carcinogenesis in BRCA mutation carriers and on adjuvant treatment in early breast cancer patients.

Investigating the Transition of Pre-Symptomatic to Symptomatic Huntington's Disease Status Based on Omics Data.

Huntington's disease is a rare neurodegenerative disease caused by a cytosine-adenine-guanine (CAG) trinucleotide expansion in the Huntingtin () gene. Although Huntington's disease (HD) is well studied, the pathophysiological mechanisms, genes and metabolites involved in HD remain poorly understood. Systems bioinformatics can reveal synergistic relationships among different omics levels and enables the integration of biological data.

An unusual combination of an atypical maternally inherited novel 0.3 Mb deletion in Williams-Beuren region and a de novo 22q11.21 microduplication in an infant with supravalvular aortic stenosis.

Williams-Beuren syndrome (WBS) is a rare neurodevelopmental disorder characterized by supravalvular aortic stenosis (SVAS), intellectual disability, overfriendliness and dysmorphic features. It is typically caused by 1.5-1.