RESUMEN
The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange and is affected by disorders including interstitial lung disease, cancer, and SARS-CoV-2-associated COVID-19 pneumonia. Investigations of these localized pathologies have been hindered by a lack of 3D in vitro human distal lung culture systems. Further, human distal lung stem cell identification has been impaired by quiescence, anatomic divergence from mouse and lack of lineage tracing and clonogenic culture. Here, we developed robust feeder-free, chemically-defined culture of distal human lung progenitors as organoids derived clonally from single adult human alveolar epithelial type II (AT2) or KRT5+ basal cells. AT2 organoids exhibited AT1 transdifferentiation potential, while basal cell organoids progressively developed lumens lined by differentiated club and ciliated cells. Organoids consisting solely of club cells were not observed. Upon single cell RNA-sequencing (scRNA-seq), alveolar organoids were composed of proliferative AT2 cells; however, basal organoid KRT5+ cells contained a distinct ITGA6+ITGB4+ mitotic population whose proliferation segregated to a TNFRSF12Ahi subfraction. Clonogenic organoid growth was markedly enriched within the TNFRSF12Ahi subset of FACS-purified ITGA6+ITGB4+ basal cells from human lung or derivative organoids. In vivo, TNFRSF12A+ cells comprised ~10% of KRT5+ basal cells and resided in clusters within terminal bronchioles. To model COVID-19 distal lung disease, we everted the polarity of basal and alveolar organoids to rapidly relocate differentiated club and ciliated cells from the organoid lumen to the exterior surface, thus displaying the SARS-CoV-2 receptor ACE2 on the outwardly-facing apical aspect. Accordingly, basal and AT2 "apical-out" organoids were infected by SARS-CoV-2, identifying club cells as a novel target population. This long-term, feeder-free organoid culture of human distal lung alveolar and basal stem cells, coupled with single cell analysis, identifies unsuspected basal cell functional heterogeneity and exemplifies progenitor identification within a slowly proliferating human tissue. Further, our studies establish a facile in vitro organoid model for human distal lung infectious diseases including COVID-19-associated pneumonia.
RESUMEN
Although there are a number of reported cases of increased cerebral blood flow during exercise, there are no reports on the relation between changes of blood flow during exercise and attentional function. The purpose of this study is to clarify the relation between changes of blood flow during exercise with AT intensity and attentional function, using near-infrared spectral analysis. The subjects were 10 healthy males. The research protocol was to conduct steady load exercise. We randomly conducted two invention trials: 1) an exercise/task trial in which a trail making test (TMT) was performed as an attentional assignment during steady load exercise, and 2) a rest/task trial in which TMT was performed during rest as a control. As a result, we observed the following: increase of oxy-Hb in the prefrontal cortex during AT exercise, the significant shortening of TMT during exercise from 69.1±10.2 seconds to63.2±7.2seconds, and, with further control, that the more oxy-Hb rises, the more TMT time is shortened. From these results, it is suggested that 10 minutes of exercise would improve attentional function, and furthermore, there is a possibility that increased cerebral blood flow may be involved with the improvement of attentional function.
RESUMEN
The aim of the present study was to examine whether amount of oral cortisol, immunoglobulin A (IgA), chromogranin A (CgA) and inflammatory cytokines, might be affected by prolonged strenuous exercise. Ten young male volunteers either exercised on recumbent ergometer at 75 % VO<sub>2</sub> max for 60 min (exercise session) or sat quietly (resting session). Saliva samples were obtained at 60 min intervals during sessions for measurements of salivary stress markers (cortisol, IgA and CgA), salivary inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and osmolality. Saliva flow rate was decreased and saliva osmolality was increased during the 60-min exercise. Saliva cortisol and CgA concentrations and secretion rates were increased during and after the exercise, whereas saliva IgA concentration and secretion rates were decreased after the exercise. Salivary inflammatory cytokines was increased during and after the exercise. The present findings suggested a single bout of prolonged strenuous exercise caused a transient increase in the salivary cortisol, CgA and inflammatory cytokines levels, whereas salivary IgA concentration and secretion rates were decreased after the exercise. Further studies, however, are needed to delineate whether or not salivary stress markers and inflammatory cytokines may be used as biological markers to determine the host responses to acute prolonged strenuous exercise.
RESUMEN
The purpose of this study was to examine the effects of aquatic exercise training on the trunk muscles function and activities of daily living in abdominal obese women. Nineteen abdominal obese (abdominal circumference: 90 cm or more) and fifteen age-matched non-obese women were recruited as participants in this study. The aquatic exercise training (60 min/day, three days/week for 8 weeks) based on abdominal twists for activating the trunk muscle function. Physical parameters, biochemical characteristics, arteriosclerotic parameters and activities of daily living scores were assessed before and after the training period. In both groups showed abdominal circumference, percent of body fat, blood pressure and lower extremity muscle strength increased significantly after aquatic exercising training. In particular, endurance capacity of abdominal and back muscles increased significantly and activities of daily living scores were significantly improved in the obese group. Moreover, the improvement in the strength of lower extremities and improvement in the activities of daily living scores, such as climbing and descending stairs, in the obese group tended to be higher than non-obese women. Additionally, in abdominal obese group, the amount of the reduction of abdominal circumference was significantly associated with that of the increase in the strength of lower extremities. Taken together, these findings suggest the possibilities that the present aquatic exercise training based on trunk muscle exercise improving the function of trunk and lower extremity muscles with reduction in the abdominal obesity, contributing to improve activities of daily living in abdominal obese women.
