p53 regulation by MDM2 contributes to self-renewal and differentiation of basal stem cells in mouse and human airway epithelium.

Proper physiological function of mammalian airways requires the differentiation of basal stem cells into secretory or multiciliated cells, among others. In addition, the self-renewal ability of these basal stem cells is crucial for developing a quick response to toxic agents in order to re-establish the epithelial barrier function of the airways. Although these epithelial missions are vital, little is known about those mechanism controlling airway epithelial regeneration in health and disease. p53 has been recently proposed as the guardian of homeostasis, promoting differentiation programs, and antagonizing a de-differentiation program. Here, we exploit mouse and human tracheal epithelial cell culture models to study the role of MDM2-p53 signaling in self-renewal and differentiation in the airway epithelium. We show that p53 protein regulation by MDM2 is crucial for basal stem cell differentiation and to keep proper cell proliferation. Therefore, we suggest that MDM2/p53 interaction modulation is a potential target to control regeneration of the mammalian airway epithelia without massively affecting the epithelium integrity and differentiation potential.

[Survival in Copd Patients with Long-Term Oxygen Therapy]. / Supervivencia en pacientes con EPOC en tratamiento con oxigenoterapia continua domiciliaria.

Introduction: Continuous home oxygen therapy (CHOT), along with smoking cessation, is the first treatment that has been shown to increase the survival of patients with chronic obstructive pulmonary disease (COPD) and chronic hypoxemia. Objective: To determine survival in a cohort of COPD patients receiving CHOT and to analyze the main causes and risk factors associated with their mortality. Methods: Prospective study of a cohort of COPD patients receiving CHOT. Numerous variables, including survival and cause of death at the end of follow-up, were collected. Results: A total of 409 COPD patients receiving CHOT were included (85.6% men; mean age: 71.27 ± 9.74 years). Mean time of CHOT follow-up was 5.86 ± 3.24 years and median survival was 6 years (95% CI: 5.47-6.53). Mortality at the end of follow-up was 75.8%, the leading cause of death being respiratory (36.9%). Longer survival was significantly associated with lower age, correct CHOT compliance, absence of exacerbations in the previous year, use of long-acting anticholinergics (LAMA), less severe COPD, presence of sleep apnea-hypopnea syndrome/obesity hypoventilation syndrome (SAHS/SHO), absence of malignant disease, heart disease, cerebrovascular disease, and kidney disease. Conclusions: The survival of COPD patients receiving CHOT was very long. The main causes of mortality were respiratory (36.9%). Independent predictors of mortality were age, presence of exacerbations in the previous year, previous diagnosis of cancer, and presence of cerebrovascular and renal disease.

Effect of a Graduated Walking Program on the Severity of Obstructive Sleep Apnea Syndrome. A Randomized Clinical Trial.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a common disease. The objective of this research was to determine the effectiveness of a graduated walking program in reducing the apnea-hypopnea index number in patients with obstructive sleep apnea syndrome (OSAS). METHODS: A randomized controlled clinical trial with a two-arm parallel in three tertiary hospitals was carried out with seventy sedentary patients with moderate to severe OSAS. Twenty-nine subjects in each arm were analyzed by protocol. The control group received usual care, while usual care and an exercise program based on progressive walks without direct supervision for 6 months were offered to the intervention group. RESULTS: The apnea-hypopnea index decreased by six points in the intervention group, and improvements in oxygen desaturation index, total cholesterol, and Low-Density Lipoprotein of Cholesterol (LDL-c) were observed. A higher decrease in sleep apnea-hypopnea index (45 ± 20.6 vs. 34 ± 26.3/h; p = 0.002) was found in patients with severe vs. moderate OSAS, as well as in oxygen desaturation index from baseline values (43.3 vs. 34.3/h; p = 0.046). Besides, High-Density Lipoprotein of Cholesterol (HDL-c) values showed a higher increase in the intervention group (45.3 vs. 49.5 mg/dL; p = 0.009) and also, a higher decrease in LDL-c was found in this group (141.2 vs. 127.5 mg/dL; p = 0.038). CONCLUSION: A home physical exercise program is a useful and viable therapeutic measure for the management of OSAS.

Oxigenoterapia domiciliaria en las enfermedades pulmonares obstructivas autores / No disponible

No disponible