Tumor Microenvironment in Sporadic Vestibular Schwannoma: A Systematic, Narrative Review.

Although diagnosis and treatment of vestibular schwannomas (VSs) improved in recent years, no factors have yet been identified as being capable of predicting tumor growth. Molecular rearrangements occur in neoplasms before any macroscopic morphological changes become visible, and the former are the underlying cause of disease behavior. Tumor microenvironment (TME) encompasses cellular and non-cellular elements interacting together, resulting in a complex and dynamic key of tumorigenesis, drug response, and treatment outcome.

Liquid Crystalline Nanoparticles Conjugated with Dexamethasone Prevent Cisplatin Ototoxicity In Vitro.

The conjugation of drugs with nanoparticles represents an innovative approach for controlled and targeted administration of therapeutic agents. Nanoparticle-based systems have been tested for the inner ear therapy, increasing the drug diffusion and being detected in all parts of the cochlea when locally applied near the round window. In this study, glycerol monooleate liquid crystalline NanoParticles were conjugated with Dexamethasone (NPD), a hydrophobic drug already used for inner ear treatments but defective in solubility and bioavailability.

Erratum: miR-199a-3p increases the anti-tumor activity of palbociclib in liver cancer models.

[This corrects the article DOI: 10.1016/j.omtn.

Characterization of a decellularized rat larynx: comparison between microscopy techniques.

Background: No effective method has yet been developed to efficiently reconstruct the larynx and restore its function. Decellularization has recently been tested for this purpose with very promising results. The goal of decellularization is to remove cells leaving an intact scaffold made of an extracellular matrix (ECM).

miR-199a-3p increases the anti-tumor activity of palbociclib in liver cancer models.

Palbociclib is in early-stage clinical testing in advanced hepatocellular carcinoma (HCC). Here, we investigated whether the anti-tumor activity of palbociclib, which prevents the CDK4/6-mediated phosphorylation of RB1 but simultaneously activates AKT signaling, could be improved by its combination with a PI3K/AKT/mTOR inhibitor in liver cancer models. The selective pan-AKT inhibitor, MK-2206, or the microRNA-199a-3p were tested in combination with palbociclib in HCC cell lines and in the TG221 HCC transgenic mouse model.

Neuron Compatibility and Antioxidant Activity of Barium Titanate and Lithium Niobate Nanoparticles.

The biocompatibility and the antioxidant activity of barium titanate (BaTiO) and lithium niobate (LiNbO) were investigated on a neuronal cell line, the PC12, to explore the possibility of using piezoelectric nanoparticles in the treatment of inner ear diseases, avoiding damage to neurons, the most delicate and sensitive human cells. The cytocompatibility of the compounds was verified by analysing cell viability, cell morphology, apoptotic markers, oxidative stress and neurite outgrowth. The results showed that BaTiO and LiNbO nanoparticles do not affect the viability, morphological features, cytochrome c distribution and production of reactive oxygen species (ROS) by PC12 cells, and stimulate neurite branching.

Hydrogen peroxide toxicity on auditory cells: An in vitro study.

In recent decades, interest has increased in the role of reactive oxygen species (ROS) in health and disease. The ROS are key causative factors in several hearing loss pathologies including ototoxicity, noise trauma, cochlear ageing and ischemic injury. In order to investigate ROS effects on inner ear cells and counteract them, we developed an in vitro model of oxidative stress by exposing the inner ear cell line OC-k3 to hydrogen peroxide (HO) at concentrations able to affect in vivo cellular components but allowing cell survival.

Upper and Lower Respiratory Signs and Symptoms in Workers Occupationally Exposed to Flour Dust.

A group of 142 bakers was studied in order to investigate the relationship between higher/lower respiratory signs/symptoms and inflammation biomarkers and occupational exposure to flour dust. A complete upper and lower respiratory tract evaluation was performed. Seven percent of bakers complained of lower respiratory symptoms, while 22% of them complained of upper respiratory symptoms.

Immune Response After Cochlear Implantation.

A cochlear implant (CI) is an electronic device that enables hearing recovery in patients with severe to profound hearing loss. Although CIs are a successful treatment for profound hearing impairment, their effectivity may be improved by reducing damages associated with insertion of electrodes in the cochlea, thus preserving residual hearing ability. Inner ear trauma leads to inflammatory reactions altering cochlear homeostasis and reducing post-operative audiological performances and electroacoustic stimulation.

Effectiveness of micronized nasal irrigations with hyaluronic acid/isotonic saline solution in non-polipoid chronic rhinosinusitis: A prospective, randomized, double-blind, controlled study.

Background: Sodium hyaluronate has been proposed as a treatment for improving the symptoms of chronic rhinosinusitis. The present study evaluated the effect of the intranasal administration of hyaluronic acid in a group of patients affected by chronic rhinosinusitis without nasal polyps (CRSsNP).

Materials And Methods: Thirty subjects aged 18-65 years affected by CRSsNP were enrolled.

Biocompatibility of glycerol monooleate nanoparticles as tested on inner ear cells.

Sensorineural hearing loss due to aging, noise exposure, trauma or drug ototoxicity is irreversible because cochlear hair cells and neurons cannot regenerate. Recently, therapeutic strategies involving nanoparticles have been developed as innovative drug delivery systems. Thermodynamically stable liquid crystalline nanoparticles based on the polar lipid glycerol monooleate (GMO NP, cubosomes), nontoxic and able to encapsulate both hydrophilic and hydrophobic compounds, were produced and tested for biocompatibility in an immortalized Organ of Corti derived cell line (OC-k3), through cell viability and cytomorphological assays, and Western blot expression profiles of apoptotic markers.

Cisplatin-Induced Ototoxicity: Updates on Molecular Targets.

Cis-diamminedichloridoplatinum (II) (cisplatin) is a chemotherapeutic drug currently prescribed for the treatment of many types of human cancer, but its use is associated with numerous adverse effects, one of which is ototoxicity. Cisplatin-induced hearing loss is mainly attributed to oxidative stress, but recent data suggest that inflammation could be the trigger event leading to inner ear cell death through endoplasmic reticulum (ER) stress, autophagy, necroptosis, and then intrinsic apoptosis. In this review, we look at the molecular targets of cisplatin, and the intracellular pathways underlying its ototoxicity.

Polydimethylsiloxanes biocompatibility in PC12 neuronal cell line.

Cochlear implants, the only way to recover from severe/profound hearing loss, may cause adverse effects, among which reactions to silicone materials coating implant electrodes, leading to apoptosis and necrosis of spiral ganglion cells. Our aim was to evaluate whether three polydimethylsiloxane (PDMS) compounds (hexadimethylsiloxane, octamethyltrisiloxane, decamethylcyclopentasiloxane) used in silicone rods could exert toxic effects on an in vitro neuronal cell model (PC12). Cell viability, morphology and mRNA expression levels of apoptotic markers were evaluated on PC12 cells at different PDMS dilutions up to 6 days of exposure.

Evaluation of toxicity of glycerol monooleate nanoparticles on PC12 cell line.

An innovative approach to improve drug delivery is the use of glycerol monooleate nanoparticles. Numerous studies describe their high versatility, low toxicity and ability to carry relatively high loads of conjugated compounds including scarcely soluble ones, providing sustained drug release and increasing drug diffusion and half-life. Despite a growing interest in their potential use for therapeutic applications, there are surprisingly few literature data concerning the toxic effects of these nanoparticles at high concentrations in vitro and in vivo, and their effects on cell metabolism.

Correction: Coenzyme Q10 plus Multivitamin Treatment Prevents Cisplatin Ototoxicity in Rats.

[This corrects the article DOI: 10.1371/journal.pone.

Regenerative medicine in hearing recovery.

Hearing loss, or deafness, affects 360 million people worldwide of which about 32 million are children. Deafness is irreversible when it involves sensory hair cell death because the regenerative ability of these cells is lost in mammals after embryo development. The therapeutic strategies for deafness include hearing aids and/or implantable devices.

Coenzyme Q10 plus Multivitamin Treatment Prevents Cisplatin Ototoxicity in Rats.

Cisplatin (Cpt) is known to induce a high level of oxidative stress, resulting in an increase of reactive oxygen species damaging the inner ear and causing hearing loss at high frequencies. Studies on animal models show that antioxidants may lower Cpt-induced ototoxicity. The aim of this study is to evaluate the ototoxic effects of two different protocols of Cpt administration in a Sprague-Dawley rat model, and to test in the same model the synergic protective effects of a solution of coenzyme Q10 terclatrate and Acuval 400®, a multivitamin supplement containing antioxidant agents and minerals (Acu-Qter).

A soft-surgery approach to minimize hearing damage caused by the insertion of a cochlear implant electrode: a guinea pig animal model.

Objective: A "soft surgery" technique was applied, using various types of specifically designed dummy electrodes, to mimic cochlear implantation in a guinea pig model, and the degree of hearing-preservation/cochlear damage was assessed.

Methods: Tricolor guinea pigs were divided into 3 groups: group A were implanted with electrodes without any contacts or wires (soft electrode), group B were implanted with electrodes having a metallic wire inside (stiff electrode), and group C underwent a cochleostomy procedure without implantation. Compound action potentials, in the range of 4 to 32 kHz, were used to assess electrophysiologic changes in the hearing function presurgery and postsurgery.

Cochlear implants and drug delivery: In vitro evaluation of dexamethasone release.

Anti-inflammatory drugs can minimize the trauma and inflammation in the inner ear caused by cochlear implantation surgery. For this reason, much effort has recently been devoted to finding the best way to administer these anti-inflammatory drugs for a prolonged time and in a personalized dosage. One solution is constructing an electrode with a dispenser filled with anti-inflammatory drugs with a dosage adapted to suit each new cochlear implant user.

Association between idiopathic hearing loss and mitochondrial DNA mutations: a study on 169 hearing-impaired subjects.

Mutations in mitochondrial DNA (mtDNA) have been shown to be an important cause of sensorineural hearing loss (SNHL). In this study, we performed a clinical and genetic analysis of 169 hearing-impaired patients and some of their relatives suffering from idiopathic SNHL, both familial and sporadic. The analysis of four fragments of their mtDNA identified several polymorphisms, the well known pathogenic mutation, A1555G, and some novel mutations in different genes, implying changes in the aminoacidic sequence.

Correlation of adverse effects of cisplatin administration in patients affected by solid tumours: a retrospective evaluation.

Cisplatin is the most common antineoplastic drug used for the therapy of solid tumours. To date, researchers have focused on the dosage to be administered for each specific tumour, mainly considering the local adverse effects. The aim of this study was to correlate the severity of the adverse effects with: i) the dosage of cisplatin; ii) the specific site of the tumour; iii) the association with other drugs; and iv) the symptoms.