Aspirin and Celecoxib Regulate Notch1/Hes1 Pathway to Prevent Pressure Overload-Induced Myocardial Hypertrophy.

This study aimed to investigate the molecular mechanisms underlying the protective effects of cyclooxygenase (cox) inhibitors against myocardial hypertrophy.Rat H9c2 cardiomyocytes were induced by mechanical stretching. SD rats underwent transverse aortic constriction to induce pressure overload myocardial hypertrophy. Rats were subjected to echocardiography and tail arterial pressure in 12W. qPCR and western blot were used to detect the expression of Notch-related signaling. The inflammatory factors were tested by ELISA in serum, heart tissue, and cell culture supernatant.Compared with control, levels of pro-inflammatory cytokines IL-6, TNF-α, and IL-1ß were increased and anti-inflammatory cytokine IL-10 was reduced in myocardial tissues and serum of rat models. Levels of Notch1 and Hes1 were reduced in myocardial tissues. However, cox inhibitor treatment (aspirin and celecoxib), the improvement of exacerbated myocardial hypertrophy, fibrosis, dysfunction, and inflammation was parallel to the activation of Notch1/Hes1 pathway. Moreover, in vitro experiments showed that, in cardiomyocyte H9c2 cells, application of ~20% mechanical stretching activated inflammatory mediators (IL-6, TNF-α, and IL-1ß) and hypertrophic markers (ANP and BNP). Moreover, expression levels of Notch1 and Hes1 were decreased. These changes were effectively alleviated by aspirin and celecoxib.Cox inhibitors may protect heart from hypertrophy and inflammation possibly via the Notch1/Hes1 signaling pathway.

Efficient resolution of 4-chlormandelic acid enantiomers using lipase@UiO-67(Zr) zirconium-organic frameworks in organic solvent.

A new biocatalyst PCL@UiO-67(Zr) was successfully synthesized by immobilized lipases on metal-organic frameworks (MOFs) materials. Compare with free lipases, zirconium foundation organic framework material UiO-67(Zr) modification on immobilized lipases Pseudomonas cepacia lipase (PCL) great boosts their enantioselectivity in the kinetic resolution racemic 4-chloro-mandelic acid (4-ClMA) on the organic solvent. The acquired bio-composite PCL@UiO-67(Zr) was fully characterized by powder X-ray diffraction (PXRD), Fourier transform infrared (FT-IR) spectroscopy, N2 adsorption-desorption isotherm and aperture distribution map, and scanning electron microscopy (SEM). The catalytic performance of PCL@UiO-67(Zr), such as temperature, reaction time, and lipase quantity, were deeply explored. The experiment results showed resolution racemic 4-ClMA optimum conditions that 20 mmol/L of (R, S)-4-chloromandelic acid, 120 mmol/L vinyl acetate, 30-mg immobilized lipases PCL@UiO-67(Zr), 2 mL of MTBE, 500 rpm, and under the 55°C reaction 18 h. In this optimum conditions, c and eep could reach up to 47.6% and 98.7%, respectively.

PEG-modified lipase immobilized onto NH2-MIL-53 MOF for efficient resolution of 4-fluoromandelic acid enantiomers.

A new heterogeneous bio-catalyst was prepared by the immobilization of lipase from Pseudomonas fluorescents (PFL) onto metal-organic frameworks (MOF), NH2-MIL-53(Fe), using covalent cross-linking. The immobilized lipase [PEG-PFL@NH2-MIL-53(Fe)] was firstly applied in enantioselective resolution of 4-fluoromandelic acid (4-FMA) enantiomers. After optimization of the immobilization PFL onto NH2-MIL-53, its loading capacity is 224.5 mg PFL/g MOF. The optimal enzymatic conditions are temperature of 50 °C, VA/4-FMA substrate ratio of 6:1, immobilized lipase loading of 60 mg and reaction time of 12 h. Experimental results show that the catalytic activity and thermal stability of PFL are significantly improved by polyethylene glycol (PEG) modification and immobilization. At 65 °C, the catalytic activity of immobilized lipase retains 86.0% of initial activity. Under the optimal conditions, the excellent results were obtained with conversion of 49.6% and enantiomer excess of 98.0% for the immobilized PFL catalyzed transesterification reaction. Furthermore, the immobilized lipase exhibits excellent cycle stability with 83% of its initial activity after four cycle.