The Role of Pericytes in Inner Ear Disorders: A Comprehensive Review.

Inner ear disorders, including sensorineural hearing loss, Meniere's disease, and vestibular neuritis, are prevalent conditions that significantly impact the quality of life. Despite their high incidence, the underlying pathophysiology of these disorders remains elusive, and current treatment options are often inadequate. Emerging evidence suggests that pericytes, a type of vascular mural cell specialized to maintain the integrity and function of the microvasculature, may play a crucial role in the development and progression of inner ear disorders.

Diet and Nutrients in Rare Neurological Disorders: Biological, Biochemical, and Pathophysiological Evidence.

: Rare diseases are a wide and heterogeneous group of multisystem life-threatening or chronically debilitating clinical conditions with reduced life expectancy and a relevant mortality rate in childhood. Some of these disorders have typical neurological symptoms, presenting from birth to adulthood. Dietary patterns and nutritional compounds play key roles in the onset and progression of neurological disorders, and the impact of alimentary needs must be enlightened especially in rare neurological diseases.

Correction: Russo et al. Involvement of Bax and Bcl-2 in Induction of Apoptosis by Essential Oils of Three Lebanese Species in Human Prostate Cancer Cells. 2018, , 292.

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Dietary Supplementation with n-3 Polyunsaturated Fatty Acids Delays the Phenotypic Manifestation of Krabbe Disease and Partially Restores Lipid Mediator Production in the Brain-Study in a Mouse Model of the Disease.

Lipid mediators from fatty acid oxidation have been shown to be associated with the severity of Krabbe disease (KD), a disorder linked to mutations in the galactosylceramidase () gene. This study aims to investigate the effects of n-3 polyunsaturated fatty acid (PUFA) supplementation on KD traits and fatty acid metabolism using Twitcher (Tw) animals as a natural model for KD. Wild-type (Wt), heterozygous (Ht), and affected Tw animals were treated orally with 36 mg n-3 PUFAs/kg body weight/day from 10 to 35 days of life.

Sex dimorphism controls dysbindin-related cognitive dysfunctions in mice and humans with the contribution of COMT.

Cognitive dysfunctions are core-enduring symptoms of schizophrenia, with important sex-related differences. Genetic variants of the DTBPN1 gene associated with reduced dysbindin-1 protein (Dys) expression negatively impact cognitive functions in schizophrenia through a functional epistatic interaction with Catechol-O-methyltransferase (COMT). Dys is involved in the trafficking of dopaminergic receptors, crucial for prefrontal cortex (PFC) signaling regulation.

Management of the Brain: Essential Oils as Promising Neuroinflammation Modulator in Neurodegenerative Diseases.

Neuroinflammation, a pivotal factor in the pathogenesis of various brain disorders, including neurodegenerative diseases, has become a focal point for therapeutic exploration. This review highlights neuroinflammatory mechanisms that hallmark neurodegenerative diseases and the potential benefits of essential oils in counteracting neuroinflammation and oxidative stress, thereby offering a novel strategy for managing and mitigating the impact of various brain disorders. Essential oils, derived from aromatic plants, have emerged as versatile compounds with a myriad of health benefits.

Nanomedicines to treat rare neurological disorders: The case of Krabbe disease.

The brain remains one of the most challenging therapeutic targets due to the low and selective permeability of the blood-brain barrier and complex architecture of the brain tissue. Nanomedicines, despite their relatively large size compared to small molecules and nucleic acids, are being heavily investigated as vehicles to delivery therapeutics into the brain. Here we elaborate on how nanomedicines may be used to treat rare neurodevelopmental disorders, using Krabbe disease (globoid cell leukodystrophy) to frame the discussion.

Red-Light-Photosensitized NO Release and Its Monitoring in Cancer Cells with Biodegradable Polymeric Nanoparticles.

The role of nitric oxide (NO) as an "unconventional" therapeutic and the strict dependence of biological effects on its concentration require the generation of NO with precise spatiotemporal control. The development of precursors and strategies to activate NO release by excitation in the so-called "therapeutic window" with highly biocompatible and tissue-penetrating red light is desirable and challenging. Herein, we demonstrate that one-photon red-light excitation of Verteporfin, a clinically approved photosensitizer (PS) for photodynamic therapy, activates NO release, in a catalytic fashion, from an otherwise blue-light activatable NO photodonor (NOPD) with an improvement of about 300 nm toward longer and more biocompatible wavelengths.

A Supramolecular Nanoassembly of Lenvatinib and a Green Light-Activatable NO Releaser for Combined Chemo-Phototherapy.

The chemotherapeutic Lenvatinib (LVB) and a nitric oxide (NO) photodonor based on a rhodamine antenna (RD-NO) activatable by the highly compatible green light are supramolecularly assembled by a β-cyclodextrin branched polymer (PolyCD). The poorly water-soluble LVB and RD-NO solubilize very well within the polymeric host leading to a ternary supramolecular nanoassembly with a diameter of ~55 nm. The efficiency of the NO photorelease and the typical red fluorescence of RD-NO significantly enhance within the polymer due to its active role in the photochemical and photophysical deactivation pathways.

Green Synthesis of Near-Infrared Plasmonic Gold Nanostructures by Pomegranate Extract and Their Supramolecular Assembling with Chemo- and Photo-Therapeutics.

Au nanostructures exhibiting a localized surface plasmon resonance in the near-infrared spectral window are obtained in a single, green step at room temperature by pomegranate extract in the presence of a highly biocompatible β-cyclodextrin branched polymer, without the need of preformed seeds, external reducing and sacrificial agents, and conventional surfactants. The polymeric component makes the Au nanostructures dispersible in water, stable for weeks and permits their supramolecular assembling with the chemotherapeutic sorafenib and a nitric oxide (NO) photodonor (NOPD), chosen as representative for chemo- and photo-therapeutics. Irradiation of the plasmonic Au nanostructures in the therapeutic window with 808 nm laser light results in a good photothermal response, which (i) is not affected by the presence of either the chemo- or the phototherapeutic guests and (ii) does not lead to their photoinduced decomposition.

Apoptosis induction of essential oils from Artemisia arborescens L. in human prostate cancer cells.

Ethnopharmacological Relevance: Prostate cancer originates from cells inside a gland, which begin to grow out of control. In the world, prostate cancer is the most common cancer in the male population. New therapeutic strategies are needed for this tumor which still has a high mortality.

A molecular dyad delivered by biodegradable polymeric nanoparticles for combined PDT and NO-PDT in cancer cells.

The design, synthesis, photochemical properties, and biological evaluation of a novel molecular dyad with double photodynamic action and its formulation within biodegradable polymeric nanoparticles (NPs) are reported. A BODIPY-based singlet oxygen (O) photosensitizer (PS) and a nitric oxide (NO) photodonor (NOPD) based on an amino-nitro-benzofurazan moiety have been covalently joined in a new molecular dyad, through a flexible alkyl spacer. Excitation of the dyad with visible light in the range 400-570 nm leads to the concomitant generation of the cytotoxic O and NO with effective quantum yields, being Φ = 0.

Physodic acid sensitizes LNCaP prostate cancer cells to TRAIL-induced apoptosis.

In spite of the extensive research for developing new therapies, prostate cancer is still one of the major human diseases with poor prognosis and high mortality. Therefore, with the aim of identifying novel agents with antigrowth and pro-apoptotic activity on prostate cancer cells, in the present study, we evaluated the effect of lichen secondary metabolite physodic acid on cell growth in human prostate cancer cells. In addition, we tested the apoptotic activity of physodic acid on TRAIL-resistant LNCaP cells in combination with TRAIL.

Dysregulation of microRNAs and tRNA-derived ncRNAs in mesothelial and mesothelioma cell lines after asbestiform fiber exposure.

Experimental evidence demonstrated that fluoro-edenite (FE) can develop chronic respiratory diseases and elicit carcinogenic effects. Environmental exposure to FE fibers is correlated with malignant pleural mesothelioma (MPM). An early diagnosis of MPM, and a comprehensive health monitoring of the patients exposed to FE fibers are two clinical issues that may be solved by the identification of specific biomarkers.

Enhancing the Anticancer Activity of Sorafenib through Its Combination with a Nitric Oxide Photodelivering β-Cyclodextrin Polymer.

In this contribution, we report a strategy to enhance the therapeutic action of the chemotherapeutic Sorafenib (SRB) through its combination with a multifunctional β-cyclodextrin-based polymer able to deliver nitric oxide (NO) and emit green fluorescence upon visible light excitation (PolyCDNO). The basically water-insoluble SRB is effectively encapsulated in the polymeric host (1 mg mL) up to a concentration of 18 μg mL. The resulting host-guest supramolecular complex is able to release SRB in sink conditions and to preserve very well the photophysical and photochemical properties of the free PolyCDNO, as demonstrated by the similar values of the NO release and fluorescence emission quantum efficiencies found.

Adaption of Lung Fibroblasts to Fluoro-Edenite Fibers: Evaluation of Molecular and Physiological Dynamics.

Background/aims: The fluoro-edenite fibrous amphibole was identified as an environmental pollutant associate to risk of carcinogenicity. In Sicily (Italy), it represents a public health issue because fluoro-edenite fibers are present in the soil of Biancavilla, a town located on the south-west slopes of the volcano Etna. Since the relationship between exposure to fluoro-edenite and the onset of lung disorders have been documented, in vitro studies were performed to clarify the mechanisms of damage, but most aspects remain unknown.

A thermoresponsive gel photoreleasing nitric oxide for potential ocular applications.

We report herein the design, preparation, characterization and biological evaluation of a thermoresponsive gel based on binary mixtures of Pluronic® co-polymers F127 and P123, the latter being covalently functionalized with a nitric oxide (NO) photodonor (NOPD). The weight ratio between the two polymeric components is optimized in order to observe gelation of their saline water solution in the range of 32-35 °C, in order to exploit the therapeutic properties of NO for potential ocular applications. Rheological measurements were performed to evaluate the gelation temperature and, hence, to select a co-polymer mixture specifically appropriate for the reference application.

Oregano (Origanum vulgare L.) essential oil provides anti-inflammatory activity and facilitates wound healing in a human keratinocytes cell model.

Skin acts as a protective barrier between the body and the external environment. Skin wounds are a common inflammatory disorder for the solution of which plants and essential oils have been applied as a medical option for centuries. Origanum vulgare essential oil (OEO) is largely used in folk medicine, but its molecular mechanisms of action are not fully known.

Functionalization of Single and Multi-Walled Carbon Nanotubes with Polypropylene Glycol Decorated Pyrrole for the Development of Doxorubicin Nano-Conveyors for Cancer Drug Delivery.

A recently reported functionalization of single and multi-walled carbon nanotubes, based on a cycloaddition reaction between carbon nanotubes and a pyrrole derived compound, was exploited for the formation of a doxorubicin (DOX) stacked drug delivery system. The obtained supramolecular nano-conveyors were characterized by wide-angle X-ray diffraction (WAXD), thermogravimetric analysis (TGA), high-resolution transmission electron microscopy (HR-TEM), and Fourier transform infrared (FT-IR) spectroscopy. The supramolecular interactions were studied by molecular dynamics simulations and by monitoring the emission and the absorption spectra of DOX.

Defense and protection mechanisms in lung exposed to asbestiform fiber: the role of macrophage migration inhibitory factor and heme oxygenase-1.

Fluoro-edenite (FE), an asbestiform fiber, is responsible for many respiratory pathologies: chronic obstructive diseases, pleural plaques, fibrosis, and malignant mesothelioma. Macrophage migration inhibitory factor (MIF) is one of the first cytokines produced in response to lung tissue damage. Heme oxygenase-1 (HO-1) is a protein with protective effects against oxidative stress.

Moscatilin, a bibenzyl derivative from the orchid Dendrobium loddigesii, induces apoptosis in melanoma cells.

The use of orchids in herbal medicine has a very long history. Dendrobium species are known to produce a variety of secondary metabolites such as phenanthrens, bibenzyls, fluorenones and sesquiterpenes, and alkaloids and are responsible for their wide variety of medicinal properties. For decades, bibenzyls, which are the main bioactive components derived from Dendrobium species, have been subjected to extensive investigation as likely candidates for cancer treatment.

Isocordoin analogues promote apoptosis in human melanoma cells via Hsp70.

Isocordin 1 and a series of 4-oxyalkyl-isocordoin analogues 2-8 were evaluated for their cytotoxicity effect against human melanoma cells (A2058). Analogues 4, 5, and 6 showed a higher inhibitory activity with IC values of 12.91 ± 0.

Screening for Krabbe disease: The first 2 years' experience.

Objectives: Globoid cell leukodystrophy or Krabbe disease is an autosomal recessive lysosomal storage disorder characterized by a deficiency in galactosylceramidase (GALC) which hydrolyses galactosylceramide and galactosylsphingosine (psychosine). The accumulation of psychosine results in the apoptosis of myelin-forming cells. The goals of this research were to identify the heterozygous carriers of Krabbe disease in Sicily (Italy), to prevent the birth of foetuses affected by this disease, and eventually in the presence of positive embryos to direct them towards a treatment before symptoms occur when it is too late to receive a useful therapy.

Increased isoprostanoid levels in brain from murine model of Krabbe disease - Relevance of isoprostanes, dihomo-isoprostanes and neuroprostanes to disease severity.

Krabbe disease (KD) is a rare and devastating pediatric leukodystrophy caused by mutations in the galactocerebrosidase (GALC) gene. The disease leads to impaired myelin formation and extensive myelin damage in the brain. Oxidative stress is implicated in the pathogenesis of KD but insofar few information is available.

Antigrowth activity and induction of apoptosis in human melanoma cells by Drymis winteri forst extract and its active components.

Melanoma is a highly invasive cancer that resists most conventional treatments. Therefore, there is an urgent need to identify alternative anticancer agents able to affect new molecular targets. Drimys winteri (Winteraceae) is a medicinal plant, employed in Brazil and many countries, in folk medicine against a variety of ailments, especially for the treatment of fevers, ulcers, pains, affections of respiratory tract and cancers.