Interplay between mTOR and Purine Metabolism Enzymes and Its Relevant Role in Cancer.

Tumor cells reprogram their metabolism to meet the increased demand for nucleotides and other molecules necessary for growth and proliferation. In fact, cancer cells are characterized by an increased "de novo" synthesis of purine nucleotides. Therefore, it is not surprising that specific enzymes of purine metabolism are the targets of drugs as antineoplastic agents, and a better knowledge of the mechanisms underlying their regulation would be of great help in finding new therapeutic approaches.

Clinical evaluation of the perception of post-trauma paresthesia in the mandible, using a biomimetic material: A preliminary study in humans.

There is a great effort from numerous research groups in the development of materials and therapeutic strategies for the functional recovery of patients who have suffered peripheral nerve injuries (PNI). In an article , the formation of a nerve bridge was observed, reconnecting the distal and proximal stumps, in the sciatic nerve of rats, indicating the effective participation of the biomaterial in the recovery of peripheral nerve injuries. For the current pilot study, 15 cases of multiple fractures of the mandible, with involvement of the inferior alveolar nerve (IAN) were selected and studied: JC (control cases) n = 6 with conventional treatment, and JT (treated cases) n = 9, with the use of biomimetic biomaterial.

Inborn Errors of Purine Salvage and Catabolism.

Cellular purine nucleotides derive mainly from de novo synthesis or nucleic acid turnover and, only marginally, from dietary intake. They are subjected to catabolism, eventually forming uric acid in humans, while bases and nucleosides may be converted back to nucleotides through the salvage pathways. Inborn errors of the purine salvage pathway and catabolism have been described by several researchers and are usually referred to as rare diseases.

The Good, the Bad and the New about Uric Acid in Cancer.

Uric acid is the final product of purine catabolism in man and apes. The serum concentration of uric acid is sex-, age- and diet-dependent and is maintained close to its maximal solubility, indicating that it plays some important role. Indeed, it has been demonstrated that, at physiological concentrations, uric acid is a powerful antioxidant, while at high intracellular concentrations, it is a pro-oxidant molecule.

Cytosolic 5'-Nucleotidase II Silencing in Lung Tumor Cells Regulates Metabolism through Activation of the p53/AMPK Signaling Pathway.

Cytosolic 5'-nucleotidase II (cN-II) is an allosteric catabolic enzyme that hydrolyzes IMP, GMP, and AMP. The enzyme can assume at least two different structures, being the more active conformation stabilized by ATP and the less active by inorganic phosphate. Therefore, the variation in ATP concentration can control both structure and activity of cN-II.

Fully automatic segmentation of sinonasal cavity and pharyngeal airway based on convolutional neural networks.

Introduction: This study aimed to test the accuracy of a new automatic deep learning-based approach on the basis of convolutional neural networks (CNN) for fully automatic segmentation of the sinonasal cavity and the pharyngeal airway from cone-beam computed tomography (CBCT) scans.

Methods: Forty CBCT scans from healthy patients (20 women and 20 men; mean age, 23.37 ± 3.

Metabolic Aspects of Adenosine Functions in the Brain.

Adenosine, acting both through G-protein coupled adenosine receptors and intracellularly, plays a complex role in multiple physiological and pathophysiological processes by modulating neuronal plasticity, astrocytic activity, learning and memory, motor function, feeding, control of sleep and aging. Adenosine is involved in stroke, epilepsy and neurodegenerative pathologies. Extracellular concentration of adenosine in the brain is tightly regulated.

Cytosolic 5'-Nucleotidase II Is a Sensor of Energy Charge and Oxidative Stress: A Possible Function as Metabolic Regulator.

Cytosolic 5'-nucleotidase II (NT5C2) is a highly regulated enzyme involved in the maintenance of intracellular purine and the pyrimidine compound pool. It dephosphorylates mainly IMP and GMP but is also active on AMP. This enzyme is highly expressed in tumors, and its activity correlates with a high rate of proliferation.

Effect of ozone therapy on wound healing in the buccal mucosa of rats.

Objective: The objective of this study was to evaluate the effects of ozone therapy on wound healing formed experimentally in the oral cavity of rats.

Design: Two surgical wounds were generated on the cheeks of 24 Wistar rats, bilaterally. Half of the animals were submitted to ozone therapy on both wounds (experimental group) and the other half received no treatment (control group).

Evaluation of pulp cavity/chamber changes after tooth-borne and bone-borne rapid maxillary expansions: a CBCT study using surface-based superimposition and deviation analysis.

Objectives: To compare volume and shape changes of pulp chamber of maxillary posterior teeth between tooth-borne and bone-borne maxillary expansions in adolescents.

Materials And Methods: This study included 36 adolescents with bilateral maxillary crossbite who received tooth-borne rapid maxillary expansion (TB group, average age 14.4 years) or bone-borne rapid maxillary expansion (BB group, average age 14.

Guided Surgery with 3D Printed Device: A Case Report.

Dental surgeons need in-depth knowledge of the bone tissue status and gingival morphology of atrophic maxillae. The aim of this study is to describe preoperative virtual planning of placement of 5 implants and to compare the plan with the actual surgical results. Three-dimensional (3D) planning of rehabilitation using software programs enables surgical guides to be specially designed for the implant site and manufactured using 3D printing.

Purine-Metabolising Enzymes and Apoptosis in Cancer.

The enzymes of both de novo and salvage pathways for purine nucleotide synthesis are regulated to meet the demand of nucleic acid precursors during proliferation. Among them, the salvage pathway enzymes seem to play the key role in replenishing the purine pool in dividing and tumour cells that require a greater amount of nucleotides. An imbalance in the purine pools is fundamental not only for preventing cell proliferation, but also, in many cases, to promote apoptosis.

Epigenetic Control of Mitochondrial Fission Enables Self-Renewal of Stem-like Tumor Cells in Human Prostate Cancer.

Cancer stem cells (CSCs) contribute to disease progression and treatment failure in human cancers. The balance among self-renewal, differentiation, and senescence determines the expansion or progressive exhaustion of CSCs. Targeting these processes might lead to novel anticancer therapies.

Analysis of Trauma Intensity during Surgical Bone Procedures Using NF-κB Expression Levels as a Stress Sensor: An Experimental Study in a Wistar Rat Model.

It is well known that the transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions and functions as a pivotal mediator of inflammatory responses. In the present study, we evaluated the trauma generated (inflammatory reaction) after osteotomy bone surgical procedures and placement of implants in the femoral cortical bone of Wistar rats. Surgical stress was evaluated measuring the release and activation of the NF-κB factor.

Emerging Role of Purine Metabolizing Enzymes in Brain Function and Tumors.

The growing evidence of the involvement of purine compounds in signaling, of nucleotide imbalance in tumorigenesis, the discovery of purinosome and its regulation, cast new light on purine metabolism, indicating that well known biochemical pathways may still surprise. Adenosine deaminase is important not only to preserve functionality of immune system but also to ensure a correct development and function of central nervous system, probably because its activity regulates the extracellular concentration of adenosine and therefore its function in brain. A lot of work has been done on extracellular 5'-nucleotidase and its involvement in the purinergic signaling, but also intracellular nucleotidases, which regulate the purine nucleotide homeostasis, play unexpected roles, not only in tumorigenesis but also in brain function.

Cytosolic 5'-Nucleotidase II Silencing in a Human Lung Carcinoma Cell Line Opposes Cancer Phenotype with a Concomitant Increase in p53 Phosphorylation.

Purine homeostasis is maintained by a purine cycle in which the regulated member is a cytosolic 5'-nucleotidase II (cN-II) hydrolyzing IMP and GMP. Its expression is particularly high in proliferating cells, indeed high cN-II activity or expression in hematological malignancy has been associated to poor prognosis and chemoresistance. Therefore, a strong interest has grown in developing cN-II inhibitors, as potential drugs alone or in combination with other compounds.

Analysis of the frequency of visualization of morphological variations in anatomical bone features in the mandibular interforaminal region through cone-beam computed tomography.

Purpose: The purpose of this study was to analyze the frequency of visualization of anatomical bone features and their possible variations in the mandibular interforaminal region through cone-beam computed tomography (CBCT).

Methods: This is a cross-sectional study that evaluated CBCT scans of the mandible of 141 women and 61 men, obtained by imaging archives from two private clinics of dental radiology. The study analyzed the frequency of visualization of: lingual symphyseal foramen (LSF), additional mental foramen (AdMF), absence of mental foramen (AbMF), mandibular incisive canal (MIC), and anterior loop (AL).

Interplay between adenylate metabolizing enzymes and AMP-activated protein kinase.

Purine nucleotides are involved in a variety of cellular functions, such as energy storage and transfer, and signalling, in addition to being the precursors of nucleic acids and cofactors of many biochemical reactions. They can be generated through two separate pathways, the de novo biosynthesis pathway and the salvage pathway. De novo purine biosynthesis leads to the formation of IMP, from which the adenylate and guanylate pools are generated by two additional steps.

Amorphous calcium phosphate (ACP) in tissue repair process.

Synthetic biomaterials submitted to new structural technologies have become ideal for the recovery of traumatized bone tissues and some bone substitutes such as bioactive glass, β-Tricalcium phosphate (β-TCP) and amorphous calcium phosphate (ACP) are being used in areas of tissue defects. For this study, ACP was produced in the form of fibers and then submitted to cytotoxicity testing. A sample of ACP was inserted into the mandibular region of a patient with a lost implant so after removal and curettage, the remaining bone site was filled with the ACP biomaterial.

Functions of the multi-interacting protein KIDINS220/ARMS in cancer and other pathologies.

Development of an organ and subsequently the whole system from an embryo is a highly integrated process. Although there is evidence that different systems are interconnected during developmental stages, the molecular understanding of this relationship is either not known or only to a limited extent. Nervous system development, amongst all, is maybe the most crucial and complex process.

A promoter-proximal transcript targeted by genetic polymorphism controls E-cadherin silencing in human cancers.

Long noncoding RNAs are emerging players in the epigenetic machinery with key roles in development and diseases. Here we uncover a complex network comprising a promoter-associated noncoding RNA (paRNA), microRNA and epigenetic regulators that controls transcription of the tumour suppressor E-cadherin in epithelial cancers. E-cadherin silencing relies on the formation of a complex between the paRNA and microRNA-guided Argonaute 1 that, together, recruit SUV39H1 and induce repressive chromatin modifications in the gene promoter.

Phase I trial of the oral smoothened inhibitor sonidegib in combination with paclitaxel in patients with advanced solid tumors.

Purpose To establish a recommended phase II dose (RP2D) for the oral smoothened inhibitor sonidegib in combination with paclitaxel; secondary objectives include evaluation of safety, tolerability, markers of Hedgehog (Hh) signaling and preliminary antitumor activity. Methods Patients with advanced solid tumors were enrolled in cohorts of escalating sonidegib dose levels (400mg, 600mg and 800mg orally, once daily on days 1-28) in combination with paclitaxel 80 mg/m on days 1, 8 and 15 in 4-weekly cycles. Dose-limiting toxicities (DLTs) were assessed using CTCAE v4.

A Small-Molecule Inhibitor of Lin28.

New discoveries in RNA biology underscore a need for chemical tools to clarify their roles in pathophysiological mechanisms. In certain cancers, synthesis of the let-7 microRNA tumor suppressor is blocked by an RNA binding protein (RBP) Lin28, which docks onto a conserved sequence in let-7 precursor RNA molecules and prevents their maturation. Thus, the Lin28/let-7 interaction might be an attractive drug target, if not for the well-known difficulty in targeting RNA-protein interactions with drugs.

Hydroxyapatite Dome for Bone Neoformation in Rabbit Tibia.

Purpose: To evaluate supracortical bone neoformation with the use of hydroxyapatite (HA) hollow domes specially manufactured for osteogenesis promotion.

Materials And Methods: Nine New Zealand rabbits were selected and 18 domes were placed, divided into three groups according to the filler: control (blood clot), vitamin complex, and particulate β-tricalcium phosphate (β-TCP). The healing period was 8 weeks, hence fluorescent markers were applied.