Oxidative Stress and Chemoradiation-Induced Oral Mucositis: A Scoping Review of In Vitro,In Vivo and Clinical Studies

Chemoradiation-induced mucositis is a debilitating condition of the gastrointestinal tract eventuating from antineoplastic treatment. It is believed to occur primarily due to oxidative stress mechanisms, which generate Reactive Oxygen Species (ROS). The aim of this scoping review was to assess the role of oxidative stress in the development of Oral Mucositis (OM). Studies from the literature, published in MEDLINE and SCOPUS, that evaluated the oxidative stress pathways or antioxidant interventions for OM, were retrieved to elucidate the current understanding of their relationship. Studies failing inclusion criteria were excluded, and those suitable underwent data extraction, using a predefined data extraction table. Eighty-nine articles fulfilled criteria, and these were sub-stratified into models of study (in vitro, in vivo, or clinical) for evaluation. Thirty-five clinical studies evaluated antioxidant interventions on OM’s severity, duration, and pain, amongst other attributes. A number of clinical studies sought to elucidate the protective or therapeutic effects of compounds that had been pre-determined to have antioxidant properties, without directly assessing oxidative stress parameters (these were deemed “indirect evidence”). Forty-seven in vivo studies assessed the capacity of various compounds to prevent OM. Findings were mostly consistent, reporting reduced OM severity associated with a reduction in ROS, malondialdehyde (MDA), myeloperoxidase (MPO), but higher glutathione (GSH) and superoxide dismutase (SOD) activity or expression. Twenty-one in vitro studies assessed potential OM therapeutic interventions. The majority demonstrated successful a reduction in ROS, and in select studies, secondary molecules were assessed to identify the mechanism. In summary, this review highlighted numerous oxidative stress pathways involved in OM pathogenesis, which may inform the development of novel therapeutic targets.     

Vacuum-based preservation of surgical specimens: An environmentally-safe step towards a formalin-free hospital

Formalin as a fixative has no practical substitutes, but is toxic and potentially carcinogenic, so caution of its use in hospitals and elsewhere is mandatory. In our hospital, preservation of surgical specimens into formalin to be transferred to pathology labs was replaced by under-vacuum sealing (UVS) tissues into plastic bags and preservation at 4 °C until transfer. Data analysis showed UVS processing to be superior in terms of staff satisfaction and of gross anatomic preservation; no problems in terms of technical feasibility or histopathologic preservation were encountered. Formalin was confined to pathology labs while its use on hospital premises was vastly reduced.     

Tunable,Grating-Gated,Graphene-On-Polyimide Terahertz Modulators

An electrically switchable graphene terahertz (THz) modulator with a tunable-by-design optical bandwidth is presented and it is exploited to compensate the cavity dispersion of a quantum cascade laser (QCL). Electrostatic gating is achieved by a metal grating used as a gate electrode, with an HfO₂/AlO_x gate dielectric on top. This is patterned on a polyimide layer, which acts as a quarter wave resonance cavity, coupled with an Au reflector underneath. The authors achieve 90% modulation depth of the intensity, combined with a 20 kHz electrical bandwidth in the 1.9–2.7 THz range. The modulator is then integrated with a multimode THz QCL. By adjusting the modulator operational bandwidth, the authors demonstrate that the graphene modulator can partially compensate the QCL cavity dispersion, resulting in an integrated laser behaving as a stable frequency comb over 35% of the operational range, with 98 equidistant optical modes and a spectral coverage ~1.2 THz. This paves the way for applications in the terahertz, such as tunable transformation-optics devices, active photonic components, adaptive and quantum optics, and metrological tools for spectroscopy at THz frequencies.     

Radiolabeled Polymeric Nanoconstructs Loaded with Docetaxel and Curcumin for Cancer Combinatorial Therapy and Nuclear Imaging

Growing evidence suggests that multifaceted diseases as cancer can be effectively tackled by hitting simultaneously different biological targets and monitoring patient‐specific responses. Combinatorial therapies, relying on the administration of two or more molecules with different cytotoxic mechanisms, are rapidly progressing in the clinic. Here, 100 nm spherical polymeric nanoconstructs (SPNs) are proposed for the combinatorial treatment of tumors by codelivering a potent antimitotic drug—docetaxel (DTXL)—and a broad spectrum anti‐inflammatory molecule—curcumin (CURC). In vitro, SPNs loaded with DTXL and CURC induce a threefold decrease in IC₅₀ as compared to DTXL‐loaded SPNs. This synergic antitumor effect is also significant in mouse models of glioblastoma multiforme, where, after 22 d of treatment, the combinatorial approach leads to complete disease regression. At 90 d post‐treatment initiation, mice injected with DTXL + CURC SPNs have a 100% survival, whereas only 50% of the DTXL SPN treated mice survive. SPNs are also labeled with radioactive ⁶⁴Cu(DOTA) molecules to document, via PET imaging, the progressive tumor mass shrinkage. Sensitization of DTXL by CURC is associated with NF‐κB downregulation and increased apoptosis. These theranostic nanoconstructs could be used for combinatorial treatment and assessment of therapeutic efficacy in other malignancies.     

Hierarchically Structured Magnetic Nanoconstructs with Enhanced Relaxivity and Cooperative Tumor Accumulation

Iron oxide nanoparticles are formidable multifunctional systems capable of contrast enhancement in magnetic resonance imaging, guidance under remote fields, heat generation, and biodegradation. Yet, this potential is underutilized in that each function manifests at different nanoparticle sizes. Here, sub‐micrometer discoidal magnetic nanoconstructs are realized by confining 5 nm ultra‐small super‐paramagnetic iron oxide nanoparticles (USPIOs) within two different mesoporous structures, made out of silicon and polymers. These nanoconstructs exhibit transversal relaxivities up to ≈10 times (r ₂ ≈ 835 mm ^?1 s^?1) higher than conventional USPIOs and, under external magnetic fields, collectively cooperate to amplify tumor accumulation. The boost in r ₂ relaxivity arises from the formation of mesoscopic USPIO clusters within the porous matrix, inducing a local reduction in water molecule mobility as demonstrated via molecular dynamics simulations. The cooperative accumulation under static magnetic field derives from the large amount of iron that can be loaded per nanoconstuct (up to ≈65 fg) and the consequential generation of significant inter‐particle magnetic dipole interactions. In tumor bearing mice, the silicon‐based nanoconstructs provide MRI contrast enhancement at much smaller doses of iron (≈0.5 mg of Fe kg^?1 animal) as compared to current practice.     

Novel multilayer modulation doped (Al,Ga)As/GaAs structures for self-aligned gate FETs

The fabrication of self-aligned gate by ion implantation modulation doped (Al,Ga)As/GaAs field effect transistors (MODFETs) utilising a novel multilayer structure capable of withstanding the high-temperature furnace anneals required for Si implant activation is reported. Typical measured extrinsic transconductances of 175 mS/mm at 300 K and 290 mS/mm at 77 K were achieved on 1.1 ?m-gate-length devices. Values of the two-dimensional electron gas saturation velocity of 1.9×107 cm/s at 300 K and 2.7×107 cm/s at 77 K were obtained from an analysis of the FET drain current/voltage characteristics using the charge-control model.     

In-House Validation and Comparison of Two Wheat (<Emphasis Type="Italic">Triticum aestivum</Emphasis>) Taxon-Specific Real-Time PCR Methods for GMO Quantification Supported by Droplet Digital PCR

Common wheat is one of the most important staple food crops worldwide. However, unlike other important staple crops such as maize or soybean, genetically modified (GM) wheat is not yet present in the global food market. Nonetheless, in the recent past, the adventitious presence of GM glyphosate-tolerant volunteers was reported in open wheat fields in the USA. The European Union Reference Laboratory for GM Food and Feed (EURL-GMFF) was therefore called to develop a strategy to detect such unauthorised GM wheat in wheat samples by using both taxon-specific and screening tests. Two candidate common wheat taxon-specific real-time PCR methods were suggested, one targeting ssII-D gene coding for starch synthase and the other targeting waxy-D1 gene, coding for granule-bound starch synthase. In the present study, the two above-mentioned real-time PCR taxon-specific methods were in-house verified and compared, proposing droplet digital PCR (ddPCR) as a new tool for supporting the application of the European Network of GMO Laboratories (ENGL) established method performance criteria. Preliminary performance data of waxy-D1 and ssII-D methods in ddPCR format are shown too to give a contribution to the bridging process from the consolidated to the emerging quantitative PCR methodology.     

Polychlorinated biphenyls and organochlorine pesticides in seafood from the Gulf of Naples (Italy)

Seven target polychlorinated biphenyls (PCBs; IUPAC nos. 28, 52, 101, 118, 138, 153, and 180) and the organochlorine pesticides (OCPs) hexachlorobenzene (HCB) and dichlorodiphenyltrichloroethane (DDT) and its related metabolites (p,p'-DDT, p,p'-DDE, and p,p'-DDD) were quantified in edible tissues from seven marine species (European hake, red mullet, blue whiting, Atlantic mackerel, blue and red shrimp, European flying squid, and Mediterranean mussel) from the Gulf of Naples in the southern Tyrrhenian Sea (Italy). PCBs 118, 138, and 153 were the dominant congeners in all the species examined. The concentrations of all PCBs (from not detectable to 15,427 ng g(-1) fat weight) exceeded those of all the DDTs (from not detectable to 1,769 ng g(-1) fat weight) and HCB (not detectable to 150.60 ng g(-1) fat weight) in the samples analyzed. The OCP concentrations were below the maximum residue limits established for fish and aquatic products by the Decreto Ministerale 13 May 2005 in all the samples analyzed; therefore the OCPs in the southern Tyrrhenian Sea species are unlikely to be a significant health hazard. Conversely, the mean concentrations of PCBs exceeded (greatly in some cases) the current limits (200 ng(-1) fat weight) set by the European Union for terrestrial foods. Although the manufacture and use of PCBs are banned or highly restricted, these compounds still are important persistent chemical contaminants in the Gulf of Naples.     

Survival of Lactobacillus rhamnosus strains in the upper gastrointestinal tract

In the present study six probiotic Lactobacillus rhamnosus strains were investigated for their ability to survive in the human upper gastrointestinal tract through a dynamic gastric model of digestion. MRS broth was used as delivery vehicle and survival was investigated during in vitro gastric and gastric plus duodenal digestion. Results highlighted that all tested strains showed good survival rate during both gastric and duodenal digestion. In particular, three strains exhibited a great survival showing a recovery percentage in the range between 117 and 276%. In agreement with survival data, high lactic acid production was detected for all strains, confirming their metabolic activity during digestion.