p57 Phosphorylation Modulates Its Localization, Stability, and Interactions.

p57 is a member of the cyclin-dependent kinase (CDK) Interacting Protein/Kinase Inhibitory Protein (CIP/Kip) family that also includes p21 and p27. Different from its siblings, few data are available about the p57 protein, especially in humans. Structurally, p57 is an intrinsically unstructured protein, a characteristic that confers functional flexibility with multiple transient interactions influencing the metabolism and roles of the protein.

Plasmon resonance biosensor for interleukin-1β point-of-care determination: A tool for early periodontitis diagnosis.

Among pro-inflammatory cytokines, Interleukin-1β is crucially involved in several inflammatory-based diseases and even cancer. Increased Interleukin-1β levels in oral fluids have been proposed as an early marker of periodontitis, a broadly diffused chronic inflammatory condition of periodontal-supporting tissues, leading eventually to tooth loss. We describe the development of a portable surface-plasmon-resonance-based optical fiber probe suitably coated with an anti-Interleukin-1β antibody monolayer.

A novel plasmonic optical-fiber-based point-of-care test for periodontal MIP-1α detection.

The analysis of salivary biomarkers as expression of periodontal health conditions has been proposed as a useful aid to conventional diagnostic approaches. In this study, we present a point-of-care test (POCT) exploiting a surface plasmon resonance (SPR)-based optical biosensor to detect salivary macrophage inflammatory protein (MIP)-1α, a promising marker of periodontitis. A plastic optical fiber (POF) was suitably modified and functionalized by an antibody self-assembled monolayer against MIP-1α for plasmonic detection.

Genome editing and cancer therapy: handling the hypoxia-responsive pathway as a promising strategy.

The precise characterization of oxygen-sensing pathways and the identification of pO-regulated gene expression are both issues of critical importance. The O-sensing system plays crucial roles in almost all the pivotal human processes, including the stem cell specification, the growth and development of tissues (such as embryogenesis), the modulation of intermediate metabolism (including the shift of the glucose metabolism from oxidative to anaerobic ATP production and vice versa), and the control of blood pressure. The solid cancer microenvironment is characterized by low oxygen levels and by the consequent activation of the hypoxia response that, in turn, allows a complex adaptive response characterized mainly by neoangiogenesis and metabolic reprogramming.

An optical fiber-based point-of-care test for periodontal MMP-8 detection: A proof of concept.

Objectives: The evaluation of salivary biomarkers has been proposed as a simple and non-invasive aid to the conventional periodontal diagnosis based on clinical-radiographic parameters. Matrix metalloproteinase-8 (MMP-8), especially in its active form, is considered one of the most reliable biomarkers of periodontitis, and point-of-care tests (POCTs) have been proposed for its clinical monitoring. In this proof-of-concept study, a novel highly sensitive POCT based on a plastic optical fiber (POF) biosensor exploiting surface plasmon resonance (SPR) to detect salivary MMP-8 is described.

Plasmonic optical fiber biosensor development for point-of-care detection of malondialdehyde as a biomarker of oxidative stress.

Numerous pieces of evidence demonstrate that oxidative stress impairs biological functions, speeds up aging, and has a role in a variety of human diseases, including systemic and oral inflammatory disorders, and even cancer. Therefore, technologies providing accurate measures of oxidative stress indicators or biomarkers appear essential in the identification/prevention of such diseases, and in their management. Particularly advantageous is the employement of point-of-care tests based on affordable and small biochips since they can quickly process biological samples and deliver results near the point of care for a prompt therapeutic intervention.

Towards a point-of-care test to cover atto-femto and pico-nano molar concentration ranges in interleukin 6 detection exploiting PMMA-based plasmonic biosensor chips.

Point-of-Care tests based on biomarkers, useful to monitor acute and chronic inflammations, are required for advances in medicine. In this scope, a key role is played by pro-inflammatory cytokines, of which interleukin 6 (IL-6) is generally thought as one of the most relevant. To use IL-6 in real scenarios, detection in ultra-low concentration ranges is required.

Hypocalcemia: A key biomarker in hospitalized COVID-19 patients.

Background: At the end of 2019 a new respiratory syndrome emerged in China named Coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection. Considering the severity of the disease in adult subjects with one or more chronic pathologies, it was mandatory to find simple and effective biomarkers for negative prognosis of the disease easily available at the admission to the hospital.

Methods: To identify possible parameters showing association with the outcome in COVID-19 patients with pre-existing chronic diseases, blood biochemical profiles of 511 patients, enrolled from March to June 2020, were retrospectively evaluated.

An Unanticipated Modulation of Cyclin-Dependent Kinase Inhibitors: The Role of Long Non-Coding RNAs.

It is now definitively established that a large part of the human genome is transcribed. However, only a scarce percentage of the transcriptome (about 1.2%) consists of RNAs that are translated into proteins, while the large majority of transcripts include a variety of RNA families with different dimensions and functions.

p27, an Intrinsically Unstructured Protein with Scaffold Properties.

The Cyclin-dependent kinase (CDK) regulator p27 is a gatekeeper of G1/S transition. It also regulates G2/M progression and cytokinesis completion, via CDK-dependent or -independent mechanisms. Recently, other important p27 functions have been described, including the regulation of cell motility and migration, the control of cell differentiation program and the activation of apoptosis/autophagy.

A Beckwith-Wiedemann-Associated Mutation Allows the Identification of a Novel Nuclear Localization Signal in Human p57.

p57 protein is a member of the CIP/Kip family, mainly localized in the nucleus where it exerts its Cyclin/CDKs inhibitory function. In addition, the protein plays key roles in embryogenesis, differentiation, and carcinogenesis depending on its cellular localization and interactors. Mutations of , the gene encoding human p57, result in the development of different genetic diseases, including Beckwith-Wiedemann, IMAGe and Silver-Russell syndromes.

A cancer-associated CDKN1B mutation induces p27 phosphorylation on a novel residue: a new mechanism for tumor suppressor loss-of-function.

CDKN1B haploinsufficiency promotes the development of several human cancers. The gene encodes p27 , a protein playing pivotal roles in the control of growth, differentiation, cytoskeleton dynamics, and cytokinesis. CDKN1B haploinsufficiency has been associated with chromosomal or gene aberrations.

Dendritic Cells and SARS-CoV-2 Infection: Still an Unclarified Connection.

The ongoing pandemic due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has so far infected about 2.42 × 10 (as at 27 August 2020) subjects with more than 820,000 deaths. It is the third zoonotic coronavirus-dependent outbreak in the last twenty years and represents a major infective threat for public health worldwide.

Effects of Germline VHL Deficiency on Growth, Metabolism, and Mitochondria.

Mutations in , which encodes von Hippel-Lindau tumor suppressor (VHL), are associated with divergent diseases. We describe a patient with marked erythrocytosis and prominent mitochondrial alterations associated with a severe germline VHL deficiency due to homozygosity for a novel synonymous mutation (c.222C→A, p.

High Dosage Lithium Treatment Induces DNA Damage and p57 Decrease.

Lithium salt is the first-line therapeutic option for bipolar disorder and has been proposed as a potential antitumoral drug. The effects of LiCl treatment were investigated in SH-SY5Y, a human neuroblastoma cell line and an in vitro model of dopaminergic neuronal differentiation. LiCl, at the dosage used in psychiatric treatment, does not affect cell proliferation, while at higher doses it delays the SH-SY5Y cell division cycle and for prolonged usage reduces cell viability.

Genetic and Epigenetic Control of CDKN1C Expression: Importance in Cell Commitment and Differentiation, Tissue Homeostasis and Human Diseases.

The gene encodes the p57 protein which has been identified as the third member of the CIP/Kip family, also including p27 and p21. In analogy with these proteins, p57 is able to bind tightly and inhibit cyclin/cyclin-dependent kinase complexes and, in turn, modulate cell division cycle progression. For a long time, the main function of p57 has been associated only to correct embryogenesis, since -ablated mice are not vital.

p27 and human cancers: A reappraisal of a still enigmatic protein.

p27 is a cell cycle regulator firstly identified as a cyclin-dependent kinase inhibitor. For a long time, its function has been associated to cell cycle progression inhibition at G1/S boundary in response to antiproliferative stimuli. The picture resulted complicated by the discovery that p27 is an intrinsically unstructured protein, with numerous CDK-dependent and -independent functions and involvement in many cellular processes, such as cytoskeleton dynamics and cell motility control, apoptosis and autophagy activation.

Multiple pathways of SIRT6 at the crossroads in the control of longevity, cancer, and cardiovascular diseases.

Sirtuin 6 (SIRT6) is a member of the sirtuin family NAD-dependent deacetylases with multiple roles in controlling organism homeostasis, lifespan, and diseases. Due to its complex and opposite functional roles, this sirtuin is considered a two-edged sword in health and disease. Indeed, SIRT6 improves longevity, similarly to the founding yeast member, silent information regulator-2 (Sir2), and modulates genome stability, telomere integrity, transcription, and DNA repair.

Tyrosine kinase inhibitors and mesenchymal stromal cells: effects on self-renewal, commitment and functions.

The hope of selectively targeting cancer cells by therapy and eradicating definitively malignancies is based on the identification of pathways or metabolisms that clearly distinguish "normal" from "transformed" phenotypes. Some tyrosine kinase activities, specifically unregulated and potently activated in malignant cells, might represent important targets of therapy. Consequently, tyrosine kinase inhibitors (TKIs) might be thought as the "vanguard" of molecularly targeted therapy for human neoplasias.

Iron overload enhances human mesenchymal stromal cell growth and hampers matrix calcification.

Background: Iron overload syndromes include a wide range of diseases frequently associated with increased morbidity and mortality. Several organs are affected in patients with iron overload including liver, heart, joints, endocrine glands, and pancreas. Moreover, severe bone and hemopoietic tissue alterations are observed.

Histone Deacetylase Inhibitors Increase p27(Kip1) by Affecting Its Ubiquitin-Dependent Degradation through Skp2 Downregulation.

Histone deacetylase inhibitors (HDACIs) represent an intriguing class of pharmacologically active compounds. Currently, some HDACIs are FDA approved for cancer therapy and many others are in clinical trials, showing important clinical activities at well tolerated doses. HDACIs also interfere with the aging process and are involved in the control of inflammation and oxidative stress.