HIF-1α has a dual role in experimental TB. This finding could have therapeutic implications because combined treatment with 2-methoxyestradiol and antibiotics appeared to eliminate mycobacteria more efficiently than conventional chemotherapy during advanced disease.
Resistance to chemotherapy hinders the successful treatment of acute lymphoblastic leukemia (ALL). The multi-drug resistance-1 (MDR1/ABCB1) gene encodes P-glycoprotein (P-gp), which plays an important role in chemoresistance; however, its transcriptional regulation remains unclear. We investigated the role of YY1 in the regulation of MDR1 and its relation to ALL outcomes. Analysis of the MDR1 promoter revealed four putative YY1-binding sites, which we analyzed using a reporter system and ChIP analysis. YY1 silencing resulted in the inhibition of MDR1 expression and function. The clinical roles of YY1 and MDR1 expression were evaluated in children with ALL. Expression of both proteins was increased in ALL patients compared to controls. We identified a positive correlation between YY1 and MDR1 expression. High levels of YY1 were associated with decreased overall survival. Our results demonstrated that YY1 regulates the transcription of MDR1. Therefore, YY1 may serve as a useful prognostic and/or therapeutic target.
Our objective was to evaluate the effects of a moderate calorie and carbohydrate-restricted diet on cardiovascular risk indicators in overweight or obese patients with prediabetes. A clinical trial was conducted in which 86 subjects presenting with overweight or obesity and prediabetes received a personalized diet of 1,200 to 1,700 calories with a distribution of 50 % carbohydrates, 20 % proteins, and 30 % fat. Body weight, fat mass, and lean mass were measured through bioimpedance. Glucose, total cholesterol, high density lipoprotein cholesterol and low density cholesterol, and triglycerides were measured. The measurements were taken at the beginning of, and at, 6 and 12 months during the intervention, and the differences were compared by paired Student's t and χ(2) tests. At 12 months, a significant reduction was noticed in body weight in patients with overweight and obesity (72.4 ± 7.8-69.6 ± 7.5 kg) (85.7 ± 14.8-80.2 ± 12.7 kg) with body mass index (28.2 ± 0.8-27.2 ± 2.1 kg/m(2)) (34.3 ± 3.5-32.1 ± 3.2 kg/m(2)), systolic (120.9 ± 14.2-112.4 ± 11.5 mmHg) (124.1 ± 11.9-115.7 ± 14.0 mmHg), diastolic blood pressures (79.0 ± 9.3-71.8 ± 8.3 mmHg) (80.4 ± 9.0-73.7 ± 13.1 mmHg), glucose (106.0 ± 8.9-95.9 ± 7.5 mg/dL) (107.3 ± 7.0-97.0 ± 8.2 mg/dL), and significant improvement on lipid profile (p < 0.05). The restrictions in the calorie and carbohydrate diet decrease the cardiovascular risk indicators in overweight or obese adults with prediabetes.
Congenital heart defects (CHD) are the third leading cause of death in children <1 year of age in Mexico where there is a high prevalence of the 677C → T polymorphism of the MTHFR gene. This is important because the homozygous 677T/T MTHFR gene and deficiency of folic acid (FA) intake have been associated with CHD. Our objective was to analyze the possible association between the genotype 677T/T of the MTHFR gene and supplementation of FA in Mexican women with the presence of complex CHD in their children. We analyzed genotypes of 31 mothers of children with complex CHD (group I) and 62 mothers of healthy children (group II) and investigated FA supplementation during pregnancy in both study groups. Allele frequencies in group I were 41.9 % for C and 58.1 % for T and 22.6 % for genotype frequencies CC, 38.7 % for CT, and 38.7 % for TT. Allele frequencies in group II were 63.7 % for C and 36.3 % for T and 38.7 % for genotype frequencies CC, 50 % for CT and 11.3 % for TT. Both populations are in Hardy-Weinberg equilibrium. Odds ratio for having a child with a complex CHD was 5.9, p = 0.008 (95 % CI 1.67; 20.63) for the TT genotype. FA supplementation at any time during pregnancy was 90.3 and 87.9 % in groups II and I respectively (p > 0.05). Association was found between the maternal genotype (677/TT MTHFR) with the presence of complex CHD in their offspring. No differences in FA supplementation during any stage were found between groups.
The Fontan procedure (FP) is the standard surgical treatment for Univentricular heart diseases. Over time, the Fontan system fails, leading to pathologies such as protein-losing enteropathy (PLE), plastic bronchitis (PB), and heart failure (HF). FP should be considered as a transitional step to the final treatment: heart transplantation (HT). This systematic review and meta-analysis aims to establish the risk of death following HT according to the presence of FP complications. There was a total of 691 transplanted patients in the 18 articles, immediate survival 88% (n = 448), survival from 1 to 5 years of 78% (n = 427) and survival from 5.1 to 10 years of 69% (n = 208), >10 years 61% (n = 109). The relative risk (RR) was 1.12 for PLE (95% confidence interval [CI] = 0.89–1.40, p = 0.34), 1.03 for HF (0.7–1.51, p = 0.88), 0.70 for Arrhythmias (0.39–1.24, p= 0.22%), 0.46 for PB (0.08–2.72, p = 0.39), and 5.81 for CKD (1.70–19.88, p = 0.005). In patients with two or more failures, the RR was 1.94 (0.99–3.81, p = 0.05). After FP, the risk of death after HT is associated with CKD and with the presence of two or more failures.
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