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81.
    
Programmed cell death ligand 1 (PD-L1) seems to rely on close relations between neoplastic and immune cells in the tumor microenvironment. Tumor to stroma ratio (TSR) has been associated with prognosis in different malignancies. The aims of this exploratory investigation were to analyze for the first time the: (i) association between TSR, PD-L1 expression and other clinical–pathological features in laryngeal squamous cell carcinoma (LSCC) biopsies and paired surgical specimens; (ii) prognostic and predictive role of TSR and PD-L1. TSR, PD-L1 expression (in terms of combined positive score [CPS]), and other clinical–pathological features were analyzed in biopsies and surgical specimens of 43 consecutive LSCC cases. A CPS < 1 evaluated on surgical specimens was associated with a low TSR (stroma rich) on both biopsies and surgical specimens (p = 0.0143 and p = 0.0063). Low TSR showed a significant negative prognostic value when evaluated on both biopsies and surgical specimens (HR = 8.808, p = 0.0003 and HR = 11.207, p = 0.0002). CPS ≥ 1 appeared to be a favorable prognostic factor (HR = 0.100, p = 0.0265). The association between bioptic and surgical specimen TSR and PD-L1 expression should be further investigated for a potential impact on targeted treatments, also with regard to immunotherapeutic protocols.  相似文献   
82.
    
The Novel Organic Cation Transporter, OCTN1, is the first member of the OCTN subfamily; it belongs to the wider Solute Carrier family SLC22, which counts many members including cation and anion organic transporters. The tertiary structure has not been resolved for any cation organic transporter. The functional role of OCNT1 is still not well assessed despite the many functional studies so far conducted. The lack of a definitive identification of OCTN1 function can be attributed to the different experimental systems and methodologies adopted for studying each of the proposed ligands. Apart from the contradictory data, the international scientific community agrees on a role of OCTN1 in protecting cells and tissues from oxidative and/or inflammatory damage. Moreover, the involvement of this transporter in drug interactions and delivery has been well clarified, even though the exact profile of the transported/interacting molecules is still somehow confusing. Therefore, OCTN1 continues to be a hot topic in terms of its functional role and structure. This review focuses on the most recent advances on OCTN1 in terms of functional aspects, physiological roles, substrate specificity, drug interactions, tissue expression, and relationships with pathology.  相似文献   
83.
    
Neuropathy development is a major dose-limiting side effect of anticancer treatments that significantly reduces patient’s quality of life. The inadequate pharmacological approaches for neuropathic pain management warrant the identification of novel therapeutic targets. Mitochondrial dysfunctions that lead to reactive oxygen species (ROS) increase, cytosolic Ca2+ imbalance, and lactate acidosis are implicated in neuropathic pain pathogenesis. It has been observed that in these deregulations, a pivotal role is played by the mitochondrial carbonic anhydrases (CA) VA and VB isoforms. Hence, preclinical studies should be conducted to assess the efficacy of two novel selenides bearing benzenesulfonamide moieties, named 5b and 5d, and able to inhibit CA VA and VB against paclitaxel-induced neurotoxicity in mice. Acute treatment with 5b and 5d (30–100 mg/kg, per os – p.o.) determined a dose-dependent and long-lasting anti-hyperalgesic effect in the Cold plate test. Further, repeated daily treatment for 15 days with 100 mg/kg of both compounds (starting the first day of paclitaxel injection) significantly prevented neuropathic pain development without the onset of tolerance to the anti-hyperalgesic effect. In both experiments, acetazolamide (AAZ, 100 mg/kg, p.o.) used as the reference drug was partially active. Moreover, ex vivo analysis demonstrated the efficacy of 5b and 5d repeated treatments in reducing the maladaptive plasticity that occurs to glia cells in the lumbar portion of the spinal cord and in improving mitochondrial functions in the brain and spinal cord that were strongly impaired by paclitaxel-repeated treatment. In this regard, 5b and 5d ameliorated the metabolic activity, as observed by the increase in citrate synthase activity, and preserved an optimal mitochondrial membrane potential (ΔΨ) value, which appeared depolarized in brains from paclitaxel-treated animals. In conclusion, 5b and 5d have therapeutic and protective effects against paclitaxel-induced neuropathy without tolerance development. Moreover, 5b and 5d reduced glial cell activation and mitochondrial dysfunction in the central nervous system, being a promising candidate for the management of neuropathic pain and neurotoxicity evoked by chemotherapeutic drugs.  相似文献   
84.
    
Classical pediatric Hodgkin Lymphoma (HL) is a rare malignancy. Therapeutic regimens for its management may be optimized by establishing treatment response early on. The aim of this study was to identify plasma protein biomarkers enabling the prediction of relapse in pediatric/adolescent HL patients treated under the pediatric EuroNet-PHL-C2 trial. We used untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics at the time of diagnosis—before any therapy—as semiquantitative method to profile plasma proteins specifically associated with relapse in 42 children with nodular sclerosing HL. In both the exploratory and the validation cohorts, six proteins (apolipoprotein E, C4b-binding protein α chain, clusterin, fibrinogen γ chain, prothrombin, and vitronectin) were more abundant in the plasma of patients whose HL relapsed (|fold change| ≥ 1.2, p < 0.05, Student’s t-test). Predicting protein function with the Gene Ontology classification model, the proteins were included in four biological processes (p < 0.01). Using immunoblotting and Luminex assays, we validated two of these candidate biomarkers—C4b-binding protein α chain and clusterin—linked to innate immune response function (GO:0045087). This study identified C4b-binding protein α chain and clusterin as candidate early plasma biomarkers of HL relapse, and important for the purpose of shedding light on the molecular scenario associated with immune response in patients treated under the EuroNet-PHL-C2 trial.  相似文献   
85.
86.
Lara A. Al-Hariri 《Polymer》2010,51(14):2993-2997
Thermal elimination of a water soluble poly(xylylidene) precursor to poly(phenylene vinylene) (PPV) was accomplished in air at 80 °C using the macro-counterion poly(ethylene glycol)-4-nonylphenyl-3-sulfopropyl ether (PEGNOPS). The high relative photoluminescence efficiency was ascribed to the low carbonyl content, with a possible contribution from PPV chain separation, which minimizes radiationless interchain exciton formation. In addition, the PEGNOPS precursor showed no carbonyl formation on long term storage, in contrast to the precursors with dodecylbenzene sulfonate and chloride counterions.  相似文献   
87.
    
The production and characterization of nanocomposites based on whey protein concentrate (WPC) and montmorilonite (MMT) incorporated with lycopene as a functional substance is presented and discussed as an alternative biomaterial for potential uses in foodstuff applications. A full factorial design with varying levels of MMT (0% and 2% in w/w) and lycopene (0%, 6%, and 12% in w/w) was used. Color, light transmission, film transparency, moisture, density, solubility, water vapor permeability, and antioxidant activity of the resulting materials were evaluated. Results indicated that lycopene and MMT nanoparticles were successfully included in WPC films using the casting/evaporation method. Inclusion of 2% w/w of MMT in the polymeric matrix significantly improved barrier property against water vapor. Lycopene, besides its good red coloring ability, provided to the films antioxidant activity and UV‐vis light protection. These findings open a new perspective for the use of materials for bioactive packaging applications.  相似文献   
88.
    
Smart metering systems have become widespread around the world. RF mesh communication systems have contributed to the creation of smarter and more reliable power systems. This paper presents an algorithm for positioning GPRS concentrators to attain delay constraints for a ZigBee‐based mesh network. The proposed algorithm determines the number and placement of concentrators using integer linear programming and a queueing model for the given mesh network. The solutions given by the proposed algorithm are validated by verifying the communication network performance through simulations.  相似文献   
89.
    
Despite its apparently intuitive nature, the acceptability limit is probably the most difficult parameter to be defined when developing a shelf life test. Although it dramatically affects the final shelf life value, it is surprising that discussion on its nature has been largely neglected in the literature and only rare indications about the possible methodologies for its determination are available in the literature. This is due to the fact that the definition of this parameter is a consumer- and market-oriented issue, requiring a rational evaluation of the potential negative consequences of food unacceptability in the actual market scenario. This paper critically analyzes the features of the acceptability limit and the role of the decision maker. The methodologies supporting the choice of the acceptability limit as well as acceptability limit values proposed in the literature to calculate shelf life of different foods are reviewed.  相似文献   
90.
Oxidation is the most common event leading to the end of shelf life of microbiologically stable foods. Thus, a reliable shelf-life assessment is crucial to verify how long the product will last before it becomes oxidized to an unacceptable level to the consumers.

Shelf-life assessment strategies of foods and beverages suffering oxidation are critically discussed focusing on definition of the acceptability limit, as well as the choice of the proper oxidative indicators, and methodologies for shelf-life testing. Testing methodologies for shelf-life determination under actual and accelerated storage conditions are considered, highlighting possible uncertainties, pitfalls, and future research needs.  相似文献   

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