Supramolecular Sensing of Chemical Warfare Agents.

AbstractChemical warfare agents are a class of organic molecules used as chemical weapons due to their high toxicity and lethal effects. For this reason, the fast detection of these compounds in the environment is crucial. Traditional detection methods are based on instrumental techniques, such as mass spectrometry or HPLC, however the use of molecular sensors able to change a detectable property (e. g., luminescence, color, electrical resistance) can be cheaper and faster. Today, molecular sensing of chemical warfare agents is mainly based on the "covalent approach", in which the sensor reacts with the analyte, or on the "supramolecular approach", which involves the formation of non‐covalent interactions between the sensor and the analyte. This Review is focused on the recent developments of supramolecular sensors of organophosphorus chemical warfare agents (from 2013). In particular, supramolecular sensors are classified by function of the sensing mechanism: i) Lewis Acids, ii) hydrogen bonds, iii) macrocyclic hosts, iv) multi‐topic sensors, v) nanosensors. It is shown how the supramolecular non‐covalent approach leads to a reversible sensing and higher selectivity towards the selected analyte respect to other interfering molecules

TGFβ impairs HNF1α functional activity in Epithelial-to-Mesenchymal Transition interfering with the recruitment of CBP/p300 acetyltransferases

The cytokine transforming growth factor β (TGFβ) plays a crucial role in the induction of both epithelial-to-mesenchymal transition (EMT) program and fibro-cirrhotic process in the liver, where it contributes also to organ inflammation following several chronic injuries. All these pathological situations greatly increase the risk of hepatocellular carcinoma (HCC) and contribute to tumor progression. In particular, late-stage HCCs are characterized by constitutive activation of TGFβ pathway and by an EMT molecular signature leading to the acquisition of invasive and metastatic properties. In these pathological conditions, the cytokine has been shown to induce the transcriptional downregulation of HNF1α, a master regulator of the epithelial/hepatocyte differentiation and of the EMT reverse process, the mesenchymal-to-epithelial transition (MET). Therefore, the restoration of HNF1α expression/activity has been proposed as targeted therapeutic strategy for liver fibro-cirrhosis and late-stage HCCs. In this study, TGFβ is found to trigger an early functional inactivation of HNF1α during EMT process that anticipates the effects of the transcriptional downregulation of its own gene. Mechanistically, the cytokine, while not affecting the HNF1α DNA-binding capacity, impaired its ability to recruit CBP/p300 acetyltransferases on target gene promoters and, consequently, its transactivating function. The loss of HNF1α capacity to bind to CBP/p300 and HNF1α functional inactivation have been found to correlate with a change of its posttranslational modification profile. Collectively, the results obtained in this work unveil a new level of HNF1α functional inactivation by TGFβ and contribute to shed light on the early events triggering EMT in hepatocytes. Moreover, these data suggest that the use of HNF1α as anti-EMT tool in a TGFβ-containing microenvironment may require the design of new therapeutic strategies overcoming the TGFβ-induced HNF1α inactivation

Functionalized Carbon Nanoparticle-Based Sensors for Chemical Warfare Agents

Real-time sensing of chemical warfare agents (CWAs) is, today, a crucial topic to prevent lethal effects of a chemical terroristic attack. For this reason, the development of efficient, selective, ..

Catalytic Degradation of Nerve Agents

Nerve agents (NAs) are a group of highly toxic organophosphorus compounds developed before World War II. They are related to organophosphorus pesticides, although they have much higher human acute toxicity than commonly used pesticides. After the detection of the presence of NAs, the critical step is the fast decontamination of the environment in order to avoid the lethal effect of these organophosphorus compounds on exposed humans. This review collects the catalytic degradation reactions of NAs, in particular focusing our attention on chemical hydrolysis. These reactions are catalyzed by different catalyst categories (metal-based, polymeric, heterogeneous, enzymatic and MOFs), all of them described in this review

Catalysis with carbon nanoparticles

Carbon nanoparticles represent a new class of nanocatalysts able to catalyze different reactions. This review collects the catalytic applications of these nanoparticles

Intact Transition Epitope Mapping—Serological Inspection by Epitope EXtraction (ITEM—SIX)

Precision medicine requests accurate serological inspections to precisely stratify patients for targeted treatment. Intact transition epitope mapping analysis proved surrogate seroconversion of a model organism’s serum when spiked with a monoclonal murine anti-Ovalbumin antibody (mAb) with epitope resolution. Isolation of the IgG fraction from blood serum applied two consecutive protein precipitation steps followed by ultrafiltration and resulted in an ESI-MS analysis-ready IgG preparation. For epitope mapping by epitope extraction, the Ovalbumin antigen was digested with trypsin. After desalting, the peptide mixture was added to the ESI-MS-ready IgG preparation from mAb-spiked serum and the solution was incubated to form an immune complex between the Ovalbumin-derived epitope peptide and the anti-Ovalbumin mAb. Then, the entire mixture of proteins and peptides was directly electrosprayed. Sorting of ions in the mass spectrometer’s gas phase, dissociation of the immune complex ions by collision-induced dissociation, and recording of the epitope peptide ion that had been released from the immune complex proved the presence of the anti-Ovalbumin mAb in serum. Mass determination of the complex-released epitope peptide ion with isotope resolution is highly accurate, guaranteeing high specificity of this novel analysis approach, which is termed Intact Transition Epitope Mapping—Serological Inspections by Epitope EXtraction (ITEM—SIX)