RESUMEN
As a rate-limiting enzyme for the serine biosynthesis pathway (SSP) in the initial step, phosphoglycerate dehydrogenase (PHGDH) is overexpressed in many different tumors, and pharmacological or genetic inhibition of PHGDH promotes antitumor effects. In the present research, by analyzing several acute myeloid leukemia (AML) datasets in the Gene Expression Omnibus (GEO), we identified prognosis-related genes and constructed a multigene signature by univariate, multivariate Cox regression and LASSO regression. Subsequently, the multigene signature was confirmed through Cox, Kaplan-Meier, and ROC analyses in the validation cohort. Moreover, PHGDH acted as a risk factor and was correlated with inferior overall survival. We further analysed other datasets and found that PHGDH was overexpressed in AML. Importantly, the expression of PHGDH was higher in drug-resistant AML compared to drug-sensitive ones. In vitro experiments showed that inhibition of PHGDH induced apoptosis and reduced proliferation in AML cells, and these antitumor effects could be related to the Bcl-2/Bax signaling pathway by the noncanonical or nonmetabolic functions of PHGDH. In summary, we constructed a twenty-gene signature that could predicate prognosis of AML patients and found that PHGDH may be a potential target for AML treatment.
RESUMEN
Silicalite-1 zeolites are widely applied in gas adsorption, catalysis, and separation due to their excellent hydrothermal stability and unique pore structure. However, traditional preparation methods have inherent drawbacks such as high pollution, high cost, etc. Therefore, this work proposed a green and efficient route for preparing Silicalite-1 zeolite by adding NH4F (F/Si = 0.1) and seeds (10 wt%) in a much shorter time (8 h) in a low-template system (TPA+/Si = 0.007). It was found that NH4F is beneficial for inhibiting the formation of SiO2. The S-1 seeds could drastically induce the formation of the zeolite skeleton structure. Noteworthy, the morphology of zeolites was determined by the relative content of NH4F and seeds. The crystal morphology is determined by the higher content of the two substances; however, when the content is similar, the crystal morphology is determined by NH4F. The results showed that simultaneous control of NH4F and seeds can suppress SiO2 formation, can improve the relative crystallinity of products, and can be precisely regulated via the synergistic effect of both in zeolite morphology. This work not only provides new ideas for regulating the morphology of silicate-1 crystals but also offers a new path for industrial large-scale production of low-cost and efficient zeolites.
RESUMEN
Diastolic heart failure (DHF) is characterized by symptoms including reduced ventricular relaxation and compliance, resulting in congestion of pulmonary and systemic circulation. The curative effects of regular cardiac agents are ineffective. Thus, new agents are required to treat chronic cardiac failure. The aim of the present study was to examine the clinical effects of the combined treatment by optimal dose of furosemide (20 mg/day) and spironolactone (40 mg/day) on elderly patients with diastolic heart failure (DHF) [New York Heart Association (NYHA) 1-2 grade]. A total of 93 patients diagnosed with DHF between February, 2013 and February, 2014 were enrolled in the present study. The patients were randomly divided into the furosemide group (20 mg/day, n=27), optimal dose group (20 mg/day furosemide+40 mg/day spirolactone, n=36), and large dose group (40 mg/day furosemide+100 mg/day spirolactone, n=30). Following treatment for one month, a comparison and analysis of the NYHA class, left ventricular ejection fraction (LVEF) and left ventricular end diastolic diameter (LVEDD), left ventricular wall segmental motion among the three groups were performed. The re-hospitalization rate of heart failure and incidence of electrolyte disorder among the three groups was compared and their differences analysed. Compared with pretreatment, the NYHA classifications of the three groups after treatment were reduced and differences were statistically significant (P<0.05). By contrast, for the NYHA classification after treatment there was no statistical significance (P>0.05). Compared with pretreatment, LVEF of the optimal dose group increased, LVEDD decreased, and the average systolic myocardial peak velocity and early diastolic myocardial peak velocity of ventricular wall motion were reduced, with differences being statistically significant (P<0.05). By contrast, in the furosemide and large dose groups no statistical significance was identified before and after the treatment (P>0.05). Improvement of the optimal dose group following treatment was more significant than the remaining two groups, and differences were statistically significant (P<0.05). The re-hospitalization rate of heart failure and incidence of electrolyte disorder in the optimal dose group following treatment were significantly less than the other two groups, and differences were statistically significant (P<0.05). In conclusion, the optimal dose (20 mg/day furosemide+40 mg/day spirolactone) significantly improved the clinical symptoms of elderly DHF patients (NYHA 1-2 grade) and ameliorated their long-term prognosis.
