BACKGROUND The shift of metabolism from mitochondrial oxidative phosphorylation to glycolysis and mitochondria binding partner of hexokinase are features common to cancer. These have been seen in pulmonary hypertension (PH) as well. An inhibitor of hexokinase 2 (HK 2), the small molecule 3-bromopyruvate (3-BrPA) is an incredibly powerful and swift-acting anticancer agent. However, whether it could be of potential benefit to PH has still been unknown. METHODS Sprague–Dawley rats with monocrotaline (MCT)-induced PH were administered 2 oral doses of 3-BrPA (15 and 30 mg/kg/day, respectively) for 14 days. Hemodynamic parameters were obtained by right heart catheterization. Histopathology, immunohistochemistry, transmission electron microscopy, flow cytometry, and assessments of relative protein expressions were conducted. RESULTS Compared with MCT treatment, 3-BrPA decreased mean pulmonary arterial pressure and pulmonary vascular resistance, and increased cardiac output. 3-BrPA significantly suppressed proliferation in addition to enhancing apoptosis of pulmonary artery smooth muscle cells, attenuating small pulmonary artery remodeling and right ventricular hypertrophy. Treatment with 3-BrPA markedly reduced the mitochondrial membrane potential and restored mitochondrial structure. Furthermore, 3-BrPA significantly inhibited HK 2 expression but not HK 1. The expression of both pyruvate dehydrogenase kinase and lactate dehydrogenase was decreased whereas that of pyruvate dehydrogenase and cytosolic cytochrome c was upregulated with 3-BrPA administration. CONCLUSION This study demonstrates the reversal of PH by 3-BrPA is related to alteration in glycolysis and improved mitochondria function, indicating the “metabolic targeting” as a rational therapeutic strategy for PH.
Coronavirus disease 2019 (COVID-19) has several extrapulmonary symptoms. Gastrointestinal (GI) symptoms are among the most frequent clinical manifestations of COVID-19, with severe consequences reported in elderly patients. Furthermore, the impact of COVID-19 on patients with pre-existing digestive diseases still needs to be fully elucidated, particularly in the older population. This review aimed to investigate the impact of COVID-19 on the GI tract, liver, and pancreas in individuals with and without previous digestive diseases, with a particular focus on the elderly, highlighting the distinctive characteristics observed in this population. Finally, the effectiveness and adverse events of the anti-COVID-19 vaccination in patients with digestive disorders and the peculiarities found in the elderly are discussed.
In this paper, the adsorption characteristics of ve sulfonamide antibiotic molecules on carbon nanotubes were investigated using density functional theory (DFT) calculations. The adsorption con gurations of different adsorption sites were optimized, and the most stable adsorption con guration of each sulfonamide molecule was determined by adsorption energy comparison, and the relative adsorption stability of ve sulfonamide molecules on carbon nanotubes was determined by comparing their adsorption energies i.e. sulfamethazine > sulfadiazine > sulfamerazine > sulfamethoxazole > sulfanilamide. The electron densities of the adsorption con gurations were then calculated to con rm that the adsorption of ve sulfonamide drug molecules on carbon nanotubes should be physical adsorption. Moreover, the adsorption energy of ve sulfonamide molecules on carbon nanotubes in the aqueous environment was larger than that in vacuum even though the adsorption process remain to be physical adsorption. The adsorption characteristics of the ve sulfonamide molecules in various acidbase environments were nally investigated. In contrast, the adsorption energies of the ve drug molecules in acid-base environments were signi cantly reduced, indicating that carbon nanotubes may need to have a suitable pH range to achieve the optimal adsorption effect when they are used for the treatment of sulfonamide antibiotics.
In this paper, the adsorption characteristics of five sulfonamide antibiotic molecules on carbon nanotubes were investigated using density functional theory (DFT) calculations. The adsorption configurations of different adsorption sites were optimized, and the most stable adsorption configuration of each sulfonamide molecule was determined by adsorption energy comparison, and the relative adsorption stability of five sulfonamide molecules on carbon nanotubes was determined by comparing their adsorption energies i.e. sulfamethazine > sulfadiazine > sulfamerazine > sulfamethoxazole > sulfanilamide. The electron densities of the adsorption configurations were then calculated to confirm that the adsorption of five sulfonamide drug molecules on carbon nanotubes should be physical adsorption. Moreover, the adsorption energy of five sulfonamide molecules on carbon nanotubes in the aqueous environment was larger than that in vacuum even though the adsorption process remain to be physical adsorption. The adsorption characteristics of the five sulfonamide molecules in various acid-base environments were finally investigated. In contrast, the adsorption energies of the five drug molecules in acid-base environments were significantly reduced, indicating that carbon nanotubes may need to have a suitable pH range to achieve the optimal adsorption effect when they are used for the treatment of sulfonamide antibiotics.
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