TRBP2, a Major Component of the RNAi Machinery, Is Subjected to Cell Cycle-Dependent Regulation in Human Cancer Cells of Diverse Tissue Origin.

Background: Transactivation Response Element RNA-binding Protein (TRBP2) is a double-stranded RNA-binding protein widely known for its critical contribution to RNA interference (RNAi), a conserved mechanism of gene-expression regulation mediated through small non-coding RNA moieties (ncRNAs). Nevertheless, TRBP2 has also proved to be involved in other molecular pathways and biological processes, such as cell growth, organism development, spermatogenesis, and stress response. Mutations or aberrant expression of TRBP2 have been previously associated with diverse human pathologies, including Alzheimer's disease, cardiomyopathy, and cancer, with TRBP2 playing an essential role(s) in proliferation, invasion, and metastasis of tumor cells.

Opportunities and barriers in omics-based biomarker discovery for steatotic liver diseases.

The rising prevalence of liver diseases related to obesity and excessive use of alcohol is fuelling an increasing demand for accurate biomarkers aimed at community screening, diagnosis of steatohepatitis and significant fibrosis, monitoring, prognostication and prediction of treatment efficacy. Breakthroughs in omics methodologies and the power of bioinformatics have created an excellent opportunity to apply technological advances to clinical needs, for instance in the development of precision biomarkers for personalised medicine. Via omics technologies, biological processes from the genes to circulating protein, as well as the microbiome - including bacteria, viruses and fungi, can be investigated on an axis.

α-Synuclein oligomers potentiate neuroinflammatory NF-κB activity and induce Ca3.2 calcium signaling in astrocytes.

Background: It is now realized that Parkinson's disease (PD) pathology extends beyond the substantia nigra, affecting both central and peripheral nervous systems, and exhibits a variety of non-motor symptoms often preceding motor features. Neuroinflammation induced by activated microglia and astrocytes is thought to underlie these manifestations. α-Synuclein aggregation has been linked with sustained neuroinflammation in PD, aggravating neuronal degeneration; however, there is still a lack of critical information about the structural identity of the α-synuclein conformers that activate microglia and/or astrocytes and the molecular pathways involved.

Microtubule Dynamics Deregulation Induces Apoptosis in Human Urothelial Bladder Cancer Cells via a p53-Independent Pathway.

Bladder cancer (BLCA) is the sixth most common type of cancer and has a dismal prognosis if diagnosed late. To identify treatment options for BLCA, we systematically evaluated data from the Broad Institute DepMap project. We found that urothelial BLCA cell lines are among the most sensitive to microtubule assembly inhibition by paclitaxel treatment.

Identifying and profiling structural similarities between Spike of SARS-CoV-2 and other viral or host proteins with Machaon.

Using protein structure to predict function, interactions, and evolutionary history is still an open challenge, with existing approaches relying extensively on protein homology and families. Here, we present Machaon, a data-driven method combining orientation invariant metrics on phi-psi angles, inter-residue contacts and surface complexity. It can be readily applied on whole structures or segments-such as domains and binding sites.

Sphingolipids Are Depleted in Alcohol-Related Liver Fibrosis.

Background & Aims: Alcohol disturbs hepatic lipid synthesis and transport, but the role of lipid dysfunction in alcohol-related liver disease (ALD) is unclear. In this biopsy-controlled, prospective, observational study, we characterized the liver and plasma lipidomes in patients with early ALD.

Methods: We performed mass spectrometry-based lipidomics of paired liver and plasma samples from 315 patients with ALD and of plasma from 51 matched healthy controls.

AGO2 localizes to cytokinetic protrusions in a p38-dependent manner and is needed for accurate cell division.

Argonaute 2 (AGO2) is an indispensable component of the RNA-induced silencing complex, operating at the translational or posttranscriptional level. It is compartmentalized into structures such as GW- and P-bodies, stress granules and adherens junctions as well as the midbody. Here we show using immunofluorescence, image and bioinformatic analysis and cytogenetics that AGO2 also resides in membrane protrusions such as open- and close-ended tubes.

From Proteomic Mapping to Invasion-Metastasis-Cascade Systemic Biomarkering and Targeted Drugging of Mutant BRAF-Dependent Human Cutaneous Melanomagenesis.

Melanoma is classified among the most notoriously aggressive human cancers. Despite the recent progress, due to its propensity for metastasis and resistance to therapy, novel biomarkers and oncogenic molecular drivers need to be promptly identified for metastatic melanoma. Hence, by employing nano liquid chromatography-tandem mass spectrometry deep proteomics technology, advanced bioinformatics algorithms, immunofluorescence, western blotting, wound healing protocols, molecular modeling programs, and MTT assays, we comparatively examined the respective proteomic contents of WM115 primary ( = 3955 proteins) and WM266-4 metastatic ( = 6681 proteins) melanoma cells.

Dicing the Disease with Dicer: The Implications of Dicer Ribonuclease in Human Pathologies.

Gene expression dictates fundamental cellular processes and its de-regulation leads to pathological conditions. A key contributor to the fine-tuning of gene expression is Dicer, an RNA-binding protein (RBPs) that forms complexes and affects transcription by acting at the post-transcriptional level via the targeting of mRNAs by Dicer-produced small non-coding RNAs. This review aims to present the contribution of Dicer protein in a wide spectrum of human pathological conditions, including cancer, neurological, autoimmune, reproductive and cardiovascular diseases, as well as viral infections.

From the Argonauts Mythological Sailors to the Argonautes RNA-Silencing Navigators: Their Emerging Roles in Human-Cell Pathologies.

Regulation of gene expression has emerged as a fundamental element of transcript homeostasis. Key effectors in this process are the Argonautes (AGOs), highly specialized RNA-binding proteins (RBPs) that form complexes, such as the RNA-Induced Silencing Complex (RISC). AGOs dictate post-transcriptional gene-silencing by directly loading small RNAs and repressing their mRNA targets through small RNA-sequence complementarity.

Targeting of copper-trafficking chaperones causes gene-specific systemic pathology in : prospective expansion of mutational landscapes that regulate tumor resistance to cisplatin.

Copper, a transition metal, is an essential component for normal growth and development. It acts as a critical co-factor of many enzymes that play key roles in diverse cellular processes. The present study attempts to investigate the regulatory functions decisively controlling copper trafficking during development and aging of the model system.

Number of Dental Stem Cells on Root Canal Dentin after Application of Triple Antibiotic Paste or Calcium Hydroxide: An In Vitro Study.

Objective: The aim of this study was to evaluate the viability of stem cells from exfoliated and deciduous teeth (SHED) on dentin surface treated with triple antibiotic paste or calcium hydroxide.

Materials And Methods: Nine single-rooted extracted premolars were prepared appropriately and divided into three groups. In group A, the root canals were left empty, a triple antibiotic paste was placed in the root canals of group B, and calcium hydroxide was placed in the root canals of group C.

Revisiting Histone Deacetylases in Human Tumorigenesis: The Paradigm of Urothelial Bladder Cancer.

Urinary bladder cancer is a common malignancy, being characterized by substantial patient mortality and management cost. Its high somatic-mutation frequency and molecular heterogeneity usually renders tumors refractory to the applied regimens. Hitherto, methotrexate-vinblastine-adriamycin-cisplatin and gemcitabine-cisplatin represent the backbone of systemic chemotherapy.

Gene-Specific Intron Retention Serves as Molecular Signature that Distinguishes Melanoma from Non-Melanoma Cancer Cells in Greek Patients.

Background: Skin cancer represents the most common human malignancy, and it includes BCC, SCC, and melanoma. Since melanoma is one of the most aggressive types of cancer, we have herein attempted to develop a gene-specific intron retention signature that can distinguish BCC and SCC from melanoma biopsy tumors.

Methods: Intron retention events were examined through RT-sqPCR protocols, using total RNA preparations derived from BCC, SCC, and melanoma Greek biopsy specimens.

Assessment of cell viability in four novel endodontic sealers.

Objective: The aim of this study was to evaluate the viability of human periodontal ligament (PDL) cells on MTA-Fillapex, GuttaFlow 2, TotalFill Sealer, and BioRoot™ RCS in comparison to conventional epoxy resin-based (AH Plus) and zinc oxide-eugenol-based (Roth's 801) sealers.

Materials And Methods: Sealers were divided into two groups, and five coverslips for each material per group were prepared. In the first group, PDLs were added immediately after the preparation of sealers (Fresh Group), and in the second, PDLs were added after 24 h.

A High-Resolution Proteomic Landscaping of Primary Human Dental Stem Cells: Identification of SHED- and PDLSC-Specific Biomarkers.

Dental stem cells (DSCs) have emerged as a promising tool for basic research and clinical practice. A variety of adult stem cell (ASC) populations can be isolated from different areas within the dental tissue, which, due to their cellular and molecular characteristics, could give rise to different outcomes when used in potential applications. In this study, we performed a high-throughput molecular comparison of two primary human adult dental stem cell (hADSC) sub-populations: Stem Cells from Human Exfoliated Deciduous Teeth (SHEDs) and Periodontal Ligament Stem Cells (PDLSCs).

Unraveling the human protein atlas of metastatic melanoma in the course of ultraviolet radiation-derived photo-therapy.

Unlabelled: To explore the photo-therapeutic capacity of UV radiation in solid tumors, we herein employed an nLC-MS/MS technology to profile the proteomic landscape of irradiated WM-266-4 human metastatic-melanoma cells. Obtained data resulted in proteomic catalogues of 5982 and 7280 proteins for UVB- and UVC-radiation conditions, respectively, and indicated the ability of UVB/C-radiation forms to eliminate metastatic-melanoma cells through induction of synergistically operating programs of apoptosis and necroptosis. However, it seems that one or more WM-266-4 cell sub-populations may escape from UV-radiation's photo-damaging activity, acquiring, besides apoptosis tolerance, an EMT phenotype that likely offers them the advantage of developing resistance to certain chemotherapeutic drugs.

Deep-proteome mapping of WM-266-4 human metastatic melanoma cells: From oncogenic addiction to druggable targets.

Cutaneous melanoma is a malignant tumor of skin melanocytes that are pigment-producing cells located in the basal layer (stratum basale) of epidermis. Accumulation of genetic mutations within their oncogenes or tumor-suppressor genes compels melanocytes to aberrant proliferation and spread to distant organs of the body, thereby resulting in severe and/or lethal malignancy. Metastatic melanoma's heavy mutational load, molecular heterogeneity and resistance to therapy necessitate the development of novel biomarkers and drug-based protocols that target key proteins involved in perpetuation of the disease.

Interaction of dental pulp stem cells with Biodentine and MTA after exposure to different environments.

Objective:: The aim of the present study was to evaluate and compare the cytotoxic effects of Biodentine and MTA on dental pulp stem cells (DPSCs) and to assess cell viability and adherence after material exposure to an acidic environment.

Material And Methods:: DPSCs were cultured either alone or in contact with either: Biodentine; MTA set for 1 hour; or MTA set for 24 hours. After 4 and 7 days, cell viability was measured using the MTT assay.

An Ethanol Extract of Hawaiian Turmeric: Extensive In Vitro Anticancer Activity Against Human Colon Cancer Cells.

Context: Turmeric (Curcuma longa) is a food spice and colorant reported to be beneficial for human health. Curcumin (diferuloylmethane) is the major ingredient in turmeric, and existing data suggest that the spice, in combination with chemotherapy, provides a superior strategy for treatment of gastrointestinal cancer. However, despite its significant effects, curcumin suffers from poor bioavailability, due to poor absorption in the body.

3-BrPA eliminates human bladder cancer cells with highly oncogenic signatures via engagement of specific death programs and perturbation of multiple signaling and metabolic determinants.

Background: Urinary bladder cancer is one of the most fatal and expensive diseases of industrialized world. Despite the strenuous efforts, no seminal advances have been achieved for its clinical management. Given the importance of metabolic reprogramming in cancer cell survival and growth, we have herein employed 3-BrPA, a halogenated derivative of pyruvate and historically considered inhibitor of glycolysis, to eliminate bladder cancer cells with highly oncogenic molecular signatures.

Dental Stem Cell Migration on Pulp Ceiling Cavities Filled with MTA, Dentin Chips, or Bio-Oss.

MTA, Bio-Oss, and dentin chips have been successfully used in endodontics. The aim of this study was to assess the adhesion and migration of dental stem cells on human pulp ceiling cavities filled with these endodontic materials in an experimental model, which mimics the clinical conditions of regenerative endodontics. Cavities were formed, by a homemade mold, on untouched third molars, filled with endodontic materials, and observed with electron microscopy.

Proteomic studies of pediatric medulloblastoma tumors with 17p deletion.

CNS tumors are the leading cause of cancer-related death in children. Medulloblastoma is the commonest pediatric CNS malignancy, wherein, despite multimodal therapy with surgery, radiation, and chemotherapy, 5 year survival rates merely approach 60%. Until present, gene expression and cytogenetic studies have produced contradicting findings regarding the molecular background of the specific disease.

Silencing of CCDC6 reduces the expression of 14-3-3σ in colorectal carcinoma cells.

Coiled-coil domain containing 6 (CCDC6) is frequently rearranged in papillary thyroid carcinomas participating in the formation of RET/PTC1 oncogene. Other rearrangements involving CCDC6 have also been identified demonstrating its high susceptibility to chromosomal recombination. Malignancies bearing CCDC6 fusion genes are developed in a background where CCDC6 is either lost or deregulated.