Stability of Surface Complexes Formed at the TiO2/Water Interface

TiO2 surface complexation by bidentate organic ligands is analysed in terms of the ligand Brønstead and Lewis basicities. The complexation and basicity constants comply with linear Gibbs Energy relationships (LGERs). For dicarboxylic acids, the surface chelate bond makes an approximately constant contribution to the stability. The proton transfer to the surface modulates the pH dependence of stability. A correlation exists between the surface complexation constant of the neutral acid H2L and the ligand first acidity constant. On the other hand, the surface complexation constants of dianions L2- of cathecols and aminophenols are positively correlated with the ligand second acidity constant. Apparent stability is determined by the competition of H+ and surface metal ions for the ligand. Stability trends are strongly influenced by the Brønstead acid base reaction between the acid ligands H2L and the surface, whereas the stability of the surface chelate contributes to the overall stability

Towards the Inhibition of Protein–Protein Interactions (PPIs) in STAT3: Insights into a New Class of Benzothiadiazole Derivatives

Signal transducer and activator of transcription 3 (STAT3) is a validated anticancer target due to the relationship between its constitutive activation and malignant tumors. Through a virtual screening approach on the STAT3-SH2 domain, 5,6-dimethyl-1H,3H-2,1,3-benzothiadiazole-2,2-dioxide (1) was identified as a potential STAT3 inhibitor. Some benzothiadiazole derivatives were synthesized by employing a versatile methodology, and they were tested by an AlphaScreen-based assay. Among them, benzosulfamide 1 showed a significant activity with an IC50 = 15.8 \ub1 0.6 \ub5M as a direct STAT3 inhibitor. Notably, we discovered that compound 1 was also able to interact with cysteine residues located around the SH2 domain. By applying mass spectrometry, liquid chromatography, NMR, and UV spectroscopy, an in-depth investigation was carried out, shedding light on its intriguing and unexpected mechanism of interaction

Towards the Inhibition of Protein–Protein Interactions (PPIs) in STAT3: Insights into a New Class of Benzothiadiazole Derivatives

Signal transducer and activator of transcription 3 (STAT3) is a validated anticancer target due to the relationship between its constitutive activation and malignant tumors. Through a virtual screening approach on the STAT3-SH2 domain, 5,6-dimethyl-1H,3H-2,1,3-benzothiadiazole-2,2-dioxide (1) was identified as a potential STAT3 inhibitor. Some benzothiadiazole derivatives were synthesized by employing a versatile methodology, and they were tested by an AlphaScreen-based assay. Among them, benzosulfamide 1 showed a significant activity with an IC50 = 15.8 ± 0.6 µM as a direct STAT3 inhibitor. Notably, we discovered that compound 1 was also able to interact with cysteine residues located around the SH2 domain. By applying mass spectrometry, liquid chromatography, NMR, and UV spectroscopy, an in-depth investigation was carried out, shedding light on its intriguing and unexpected mechanism of interaction

Tuning PFKFB3 Bisphosphatase Activity Through Allosteric Interference

The human inducible phospho-fructokinase bisphosphatase isoform 3, PFKFB3, is a crucial regulatory node in the cellular metabolism. The enzyme is an important modulator regulating the intracellular fructose-2,6-bisphosphate level. PFKFB3 is a bifunctional enzyme with an exceptionally high kinase to phosphatase ratio around 740:1. Its kinase activity can be directly inhibited by small molecules acting directly on the kinase active site. On the other hand, here we propose an innovative and indirect strategy for the modulation of PFKFB3 activity, achieved through allosteric bisphosphatase activation. A library of small peptides targeting an allosteric site was discovered and synthesized. The binding affinity was evaluated by microscale thermophoresis (MST). Furthermore, a LC-MS/MS analytical method for assessing the bisphosphatase activity of PFKFB3 was developed. The new method was applied for measuring the activation on bisphosphatase activity with the PFKFB3-binding peptides. The molecular mechanical connection between the newly discovered allosteric site to the bisphosphatase activity was also investigated using both experimental and computational methods

Differentially Expressed Proteins in Primary Endothelial Cells Derived From Patients With Acute Myocardial Infarction

Endothelial dysfunction is one of the primary factors in the onset and progression of atherothrombosis resulting in acute myocardial infarction (AMI). However, the pathological and cellular mechanisms of endothelial dysfunction in AMI have not been systematically studied. Protein expression profiling in combination with a protein network analysis was used by the mass spectrometry-based label-free quantification approach. This identified and quantified 2246 proteins, of which 335 were differentially regulated in coronary arterial endothelial cells from patients with AMI compared with controls. The differentially regulated protein profiles reveal the alteration of (1) metabolism of RNA, (2) platelet activation, signaling, and aggregation, (3) neutrophil degranulation, (4) metabolism of amino acids and derivatives, (5) cellular responses to stress, and (6) response to elevated platelet cytosolic Ca2+ pathways. Increased production of oxidants and decreased production of antioxidant biomarkers as well as downregulation of proteins with antioxidant properties suggests a role for oxidative stress in mediating endothelial dysfunction during AMI. In conclusion, this is the first quantitative proteomics study to evaluate the cellular mechanisms of endothelial dysfunction in patients with AMI. A better understanding of the endothelial proteome and pathophysiology of AMI may lead to the identification of new drug targets

Profiling Vaccinium macrocarpon components and metabolites in human urine and the urine ex-vivo effect on Candida albicans adhesion and biofilm-formation

The aim of this work was to profile, by using an HPLC-MS/MS method, cranberry compounds and metabolites found in human urine after ingestion of a highly standardized cranberry extract (Anthocran\uae). Two different strategies were adopted for the data analysis: a targeted and an untargeted approach. These strategies allowed the identification of 42 analytes including cranberry components, known metabolites and metabolites hitherto unreported in the literature, including six valerolactones/valeric acid derivatives whose presence in urine after cranberry consumption has never been described before. Absolute concentrations of 26 over 42 metabolites were obtained by using pure available standards. Urine collected at different time points after the last dosage of Anthocran\uae were tested on the reference strain C. albicans SC5314, a biofilm-forming strain. Fractions collected after 12 h were found to significantly reduce the adhesion and biofilm formation compared to the control (p < 0.05). A similar effect was then obtained by using Anthocran\u2122 Phytosome\u2122, the lecithin formulation containing 1/3 of standardized cranberry extract and formulated to enhance the absorption of the cranberry components. The urinary profile of cranberry components and metabolites in the urine fractions collected at 1 h, 6 h and 12 h after the last capsule intake were then reproduced by using the pure standards at the concentration ranges found in the urine fraction, and tested on C. albicans. Only the mixture mimicking the urinary fraction collected at 12 h and containing as main components, quercetin and 5-(3',4'-dihydroxyphenyl)-\u3b3-valerolactone was found effective thus confirming the ex-vivo results

Phenolic profile and biological activity of table grapes (Vitis vinifera L.)

Table grapes are largely produced and consumed in the Mediterranean area. Furthermore, in the last years, the commercial interest in table grapes and other non-alcoholic grape products has notably increased worldwide. In addition to the nutritional aspects, polyphenol compounds in fresh grapes could exert positive effects on human health. The aim of this study was the characterization of the phenolic pattern of sixteen grape varieties and the evaluation of the associated antioxidant capacity and anti-inflammatory activity at gastric level. The methods used were: 1) Folin-Cocalteau\u2019s assay for the quantification of total polyphenol content; 2) High-Performance Liquid Chromatography (HPLC) coupled with Diode-Array Detector (DAD) to perform the quantitative analysis of grapes phenolic fraction 3) DPPH (1,1,-diphenil-2-picrylhydrazyl) spectrophotometric assay for the assessment of radical scavenging activity; 4) assessment of IL-8 release from human gastric epithelial cells to evaluate the anti-inflammatory activity of grape extracts. Some grapes, including seedless varieties, showed that the phenolic pattern was highly correlated with the biological activities, and, in particular, with peel and seeds portion. These results suggest that selected grape varieties could represent, also for consumers who do not drink wine, a source of healthy compounds potentially able to counteract oxidative stress and gastric inflammation