Several proteomics studies have been conducted to identify new cerebrospinal fluid (CSF) biomarkers in Multiple Sclerosis (MuS). However, the complexity of CSF and its invasive collection, limits its ...use. Therefore, the goal of biomarker research in MuS is to identify novel distinctive targets in CSF or in easily accessible biofluids. Tears represent an interesting matrix for this purpose, because (1) tears are related to the central nervous system (CNS) and (2) the CNS contains Extracellular Vesicles (EVs) derived from brain cells. These EVs are emerging new biomarkers associated to several neurological disorders. Here we applied an optimized flow cytometer for the identification and subtyping of EVs from CSF and tears. We found, for the first time, microglia-derived and neural-derived EVs in tears. The flow cytometer was used to sort and purify 106 EVs from untouched CSF and tears of MuS patients and healthy subjects. Purified EVs were analyzed with shotgun proteomics analysis, revealing that EVs from both CSF and tears of MuS patients conveyed similar proteins. Our data demonstrated a specific EVs-mediated molecular cross talk between CSF and tears, which opens the door to new diagnostic perspectives for MuS.
Data are available via ProteomeXchange with identifier PXD013794.
Proteomics characterization of released Extracellular Vesicles (EVs) in CSF and tears of Multiple Sclerosis patients represents a pioneering application that helped in recognizing information about the biologically relevant molecules. We found, for the first time, microglia-derived and neural-derived EVs in tears. Moreover, purified EVs revealed that both CSF and tears of Multiple Sclerosis patients conveyed similar proteins involved in inflammation, angiogenesis and immune response signalling. We think that our data will contribute to enhance knowledge in Multiple Sclerosis mechanisms and help in biomarker discovery. Moreover tears represent one of the most convenient body fluid for biomarker discovery in Multiple Sclerosis, since it is an high informative and easy accessible. The opportunity to export such a platform to a territory monitoring plan opens the door to new diagnostic perspectives for Multiple Sclerosis.
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•Extracellular vesicles (EVs) FACS- purified have been used for proteomics.•Microglia-derived and neural-derived EVs were identified in tears.•Tears and CSF EVs convey similar proteins, in Multiple Sclerosis.•EV proteins deliver nuclear information and the program to insert it into the target cells.
Helicobacter pylori
colonizes approximately 50% of the world’s population, and it is the cause of chronic gastritis, peptic ulcer disease, and gastric cancer. The increase of antibiotic resistance is ...one of the biggest challenges of our century due to its constant increase. In order to identify an alternative or adjuvant strategy to the standard antibiotic therapy, the
in vitro
activity of newly synthesized Silver Ultra-NanoClusters (SUNCs), characterized by an average size inferior to 5 nm, against clinical strains of
H. pylori
, with different antibiotic susceptibilities, was evaluated in this study. MICs and MBCs were determined by the broth microdilution method, whereas the effect of drug combinations was determined by the checkerboard assay. The Minimum Biofilm Eradication Concentration (MBEC) was measured using AlamarBlue (AB) assay and colony-forming unit (CFU) counts. The cytotoxicity was evaluated by performing the MTT assay on the AGS cell line. The inhibitory activity was expressed in terms of bacteriostatic and bactericidal potential, with MIC
50
, MIC
90
, and MBC
50
of 0.33 mg/L against planktonic
H. pylori
strains. Using the fractional inhibitory concentration index (FICI), SUNCs showed potential synergism with metronidazole and clarithromycin. The biofilm eradication was obtained after treatment with 2×, 3×, and 4× MIC values. Moreover, SUNCs showed low toxicity on human cells and were effective in eradicating a mature biofilm produced by
H. pylori
. The data presented in this study demonstrate that SUNCs could represent a novel strategy for the treatment of
H. pylori
infections either alone or in combination with metronidazole.
The cyclic nucleotides, cAMP and cGMP, are ubiquitous second messengers responsible for translating extracellular signals to intracellular biological responses in both normal and tumor cells. When ...these signals are aberrant or missing, cells may undergo neoplastic transformation or become resistant to chemotherapy. cGMP-hydrolyzing phosphodiesterases (PDEs) are attracting tremendous interest as drug targets for many diseases, including cancer, where they regulate cell growth, apoptosis and sensitization to radio- and chemotherapy. In breast cancer, PDE5 inhibition is associated with increased intracellular cGMP levels, which is responsible for the phosphorylation of PKG and other downstream molecules involved in cell proliferation or apoptosis. In this review, we provide an overview of the most relevant studies regarding the controversial role of PDE inhibitors as off-label adjuvants in cancer therapy.
Cannabidiol (CBD) and cannabigerol (CBG) are
terpenophenols. Although CBD's effectiveness against neurological diseases has already been demonstrated, nothing is known about CBG. Therefore, a ...comparison of the effects of these compounds was performed in two experimental models mimicking the oxidative stress and neurotoxicity occurring in neurological diseases. Rat astrocytes were exposed to hydrogen peroxide and cell viability, reactive oxygen species production and apoptosis occurrence were investigated. Cortexes were exposed to K
60 mM depolarizing stimulus and serotonin (5-HT) turnover, 3-hydroxykinurenine and kynurenic acid levels were measured. A proteomic analysis and bioinformatics and docking studies were performed. Both compounds exerted antioxidant effects in astrocytes and restored the cortex level of 5-HT depleted by neurotoxic stimuli, whereas sole CBD restored the basal levels of 3-hydroxykinurenine and kynurenic acid. CBG was less effective than CBD in restoring the levels of proteins involved in neurotransmitter exocytosis. Docking analyses predicted the inhibitory effects of these compounds towards the neurokinin B receptor.
The results in the in vitro system suggest brain non-neuronal cells as a target in the treatment of oxidative conditions, whereas findings in the ex vivo system and docking analyses imply the potential roles of CBD and CBG as neuroprotective agents.
Pancreatic β cell failure is key to type 2 diabetes (T2D) onset and progression. Here, we assess whether human β cell dysfunction induced by metabolic stress is reversible, evaluate the molecular ...pathways underlying persistent or transient damage, and explore the relationships with T2D islet traits. Twenty-six islet preparations are exposed to several lipotoxic/glucotoxic conditions, some of which impair insulin release, depending on stressor type, concentration, and combination. The reversal of dysfunction occurs after washout for some, although not all, of the lipoglucotoxic insults. Islet transcriptomes assessed by RNA sequencing and expression quantitative trait loci (eQTL) analysis identify specific pathways underlying β cell failure and recovery. Comparison of a large number of human T2D islet transcriptomes with those of persistent or reversible β cell lipoglucotoxicity show shared gene expression signatures. The identification of mechanisms associated with human β cell dysfunction and recovery and their overlap with T2D islet traits provide insights into T2D pathogenesis, fostering the development of improved β cell-targeted therapeutic strategies.
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•Human β cell dysfunction induced by metabolic stress may be persistent or transient•Specific transcriptomic changes associate with durable or reversible damage•Type 2 diabetes (T2D) β cells have several functional and molecular alterations•T2D and irreversibly or temporarily impaired β cells share key transcriptome traits
Marselli et al. find that human β cell dysfunction induced by metabolic stresses is persistent or transient. RNA sequencing and eQTL analysis identify key pathways underlying failure and recovery. Type 2 diabetes β cells have several functional and molecular alterations and share specific transcriptomic traits of β cells with irreversible or rescuable damage.
Purinergic Signaling in Oral Tissues Zuccarini, Mariachiara; Giuliani, Patricia; Ronci, Maurizio ...
International journal of molecular sciences,
07/2022, Volume:
23, Issue:
14
Journal Article
Peer reviewed
Open access
The role of the purinergic signal has been extensively investigated in many tissues and related organs, including the central and peripheral nervous systems as well as the gastrointestinal, ...cardiovascular, respiratory, renal, and immune systems. Less attention has been paid to the influence of purines in the oral cavity, which is the first part of the digestive apparatus and also acts as the body’s first antimicrobial barrier. In this review, evidence is provided of the presence and possible physiological role of the purinergic system in the different structures forming the oral cavity including teeth, tongue, hard palate, and soft palate with their annexes such as taste buds, salivary glands, and nervous fibers innervating the oral structures. We also report findings on the involvement of the purinergic signal in pathological conditions affecting the oral apparatus such as Sjögren’s syndrome or following irradiation for the treatment of head and neck cancer, and the use of experimental drugs interfering with the purine system to improve bone healing after damage. Further investigations are required to translate the results obtained so far into the clinical setting in order to pave the way for a wider application of purine-based treatments in oral diseases.
The aim of this work was to deeply investigate the structure and properties of electrochemically synthesized silver nanoparticles (AgNPs) through high-resolution techniques such as transmission ...electron microscopy (TEM), scanning electron microscopy (SEM), Zeta Potential measurements, and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Strong brightness, tendency to generate nanoclusters containing an odd number of atoms, and absence of the free silver ions in solution were observed. The research also highlighted that the chemical and physical properties of the AgNPs seemed to be related to their peculiar oxidative state as suggested by X-ray photoelectron spectroscopy (XPS) and X-ray powder diffraction (XRPD) analyses. Finally, the MTT assay tested the low cytotoxicity of the investigated AgNPs.
The low-density-lipoprotein receptors represent a family of pleiotropic cell surface receptors involved in lipid homeostasis, cell migration, proliferation and differentiation. The family shares ...common structural features but also has significant differences mainly due to tissue-specific interactors and to peculiar proteolytic processing. Among the receptors in the family, recent studies place low-density lipoprotein receptor-related protein 8 (LRP8) at the center of both neurodegenerative and cancer-related pathways. From one side, its overexpression has been highlighted in many types of cancer including breast, gastric, prostate, lung and melanoma; from the other side, LRP8 has a potential role in neurodegeneration as apolipoprotein E (ApoE) and reelin receptor, which are, respectively, the major risk factor for developing Alzheimer’s disease (AD) and the main driver of neuronal migration, and as a γ-secretase substrate, the main enzyme responsible for amyloid formation in AD. The present review analyzes the contributions of LDL receptors, specifically of LRP8, in both cancer and neurodegeneration, pointing out that depending on various interactions and peculiar processing, the receptor can contribute to both proliferative and neurodegenerative processes.
The autonomic nervous system (ANS) plays a crucial role both in acute and chronic psychological stress eliciting changes in many local and systemic physiological and biochemical processes. Salivary ...secretion is also regulated by ANS. In this study, we explored salivary proteome changes produced in thirty-eight University students by a test stress, which simulated an oral exam. Students underwent a relaxation phase followed by the stress test during which an electrocardiogram was recorded. To evaluate the effect of an olfactory stimulus, half of the students were exposed to a pleasant odor diffused in the room throughout the whole session. Saliva samples were collected after the relaxation phase (T0) and the stress test (T1). State anxiety was also evaluated at T0 and T1. Salivary proteins were separated by two-dimensional electrophoresis, and patterns at different times were compared. Spots differentially expressed were trypsin digested and identified by mass spectrometry. Western blot analysis was used to validate proteomic results. Anxiety scores and heart rate changes indicated that the fake exam induced anxiety. Significant changes of α-amylase, polymeric immunoglobulin receptor (PIGR), and immunoglobulin α chain (IGHA) secretion were observed after the stress test was performed in the two conditions. Moreover, the presence of pleasant odor reduced the acute social stress affecting salivary proteome changes. Therefore, saliva proteomic analysis was a useful approach to evaluate the rapid responses associated to an acute stress test also highlighting known biomarkers.
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