RESUMEN
Background: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition resulting from mutations in the alpha-1 antitrypsin (AAT) protein, a major systemic antiproteinase, resulting in reduced/no release of AAT, disrupting the proteinase/antiproteinase balance. A sustained imbalance can cause structural changes to the lung parenchyma, leading to emphysema. Predicting and assessing human responses to potential therapeutic candidates from preclinical animal studies have been challenging. Our aims were to develop a more physiologically relevant in vitro model of the proteinase/antiproteinase balance and assess whether the data generated could better predict the efficacy of pharmacological candidates to inform decisions on clinical trials, together with expected biomarker responses. Methods: We developed an in vitro model assessing the proteinase/antiproteinase balance by the changes in the fibrinogen cleavage products of neutrophil elastase (NE) and proteinase 3 (PR3). This allowed the assessment of physiological and pharmaceutical neutrophil serine proteinase (NSP) inhibitors to determine the putative threshold at which the maximal effect is achieved. Results: AAT significantly reduced NE and PR3 activity footprints, with the maximal reduction achieved at concentrations above 10 µM. The inhibitor MPH966 alone also significantly reduced NE footprint generation in a concentration-dependent manner, leveling out above 100 nM but had no effect on the PR3 footprint. At levels of AAT consistent with AATD, MPH966 had an additive effect, reducing the NE activity footprint more than either inhibitor alone. Conclusion: Our results support an inhibitor threshold above which the activity footprint generation appears resistant to increasing dosage. Our model can support the testing of inhibitors, confirming activity biomarkers as indicators of likely pharmaceutical efficacy, the assessment of NSP activity in the pathophysiology of emphysema, and the likely function of biological or pharmacological inhibitors in disease management.
RESUMEN
Over the past decades, the presence of pharmaceutical emerging contaminants in water bodies is receiving increasing attention due to the high concentration detected from wastewater effluent. Water systems contain a wide range of components coexisting together, which increases the difficulty of removing pollutants from the water. In order to achieve selective photodegradation and to enhance the photocatalytic activity of the photocatalyst on emerging contaminants, a Zr-based metal-organic framework (MOF), termed VNU-1 (VNU represents Vietnam National University) constructed with ditopic linker 1,4-bis(2-[4-carboxyphenyl]ethynyl)benzene (H2CPEB), with enlarged pore size and ameliorated optical properties, was synthesized and applied in this study. When compared to UiO-66 MOFs, which only had 30% photodegradation of sulfamethoxazole, VNU-1 had 7.5 times higher adsorption and reached 100% photodegradation in 10 min. The tailored pore size of VNU-1 resulted in size-selective properties between small-molecule antibiotics and big-molecule humic acid, and VNU-1 maintained high photodegradation performance after 5 cycles. Based on the toxicity test and the scavenger test, the products after photodegradation had no toxic effect on V. fischeri bacteria, and the superoxide radical (·O2-) and holes (h+) generated from VNU-1 dominated the photodegradation reaction. These results demonstrate that VNU-1 is a promising photocatalyst and provide a new insight for developing MOF photocatalyst to remove emerging contaminants in the wastewater systems.
RESUMEN
Metal-organic framework (MOF) in biomass valorization is a promising technology developed in recent decades. By tailoring both the metal nodes and organic ligands, MOFs exhibit multiple functionalities, which not only extend their applicability in biomass conversion but also increase the complexity of material designs. To address this issue, quantum mechanical simulations have been used to provide mechanistic insights into the catalysis of biomass-derived molecules, which could potentially facilitate the development of novel MOF-based materials for biomass valorization. The aim of this review is to survey recent quantum mechanical simulations on biomass reactions occurring in MOF catalysts, with the emphasis on the studies of the catalytic activity of active sites and the effects of organic ligand and porous structures on the kinetics. Moreover, different model systems and computational methods used for MOF simulations are also surveyed and discussed in this review.
RESUMEN
The heterogeneous metal-organic framework Bi-BTC successfully catalyzed the synthesis of para-xylene from bio-based 2,5-dimethylfuran and acrylic acid in a promising yield (92 %), under relatively mild conditions (160 °C, 10â bar), and with a low reaction-energy barrier (47.3â kJ mol-1 ). The proposed reaction strategy also demonstrates a remarkable versatility for furan derivatives such as furan and 2-methylfuran.