Bacterial metabolite S-equol modulates glucagon-like peptide-1 secretion from enteroendocrine L cell line GLUTag cells via actin polymerization.

S-equol is one of gut bacterial metabolites produced from soybean isoflavone daizein. While S-equol is known to promote glucose-induced insulin secretion from pancreatic ß cells, whether S-equol affects glucagon-like peptide-1 (GLP-1) secretion from enteroendoceine L cells remains unclear. Here we assessed the effect of S-equol on GLP-1 secretion from mouse enteroendocrine L cell line GLUTag cells. GLUTag cells expressed GPR30 and estrogen receptors, which are putative S-equol receptors. Application of S-equol induced an increase in intracellular Ca2+ levels via GPR30. However, S-equol did not enhance GLP-1 exocytosis, and long-term treatment of S-equol suppressed GLP-1 secretion. Moreover, immunocytochemistry revealed that S-equol increased the density of cortical actin filaments via G12/13 signaling under GPR30. These data suggest that S-equol prevents GLP-1 secretion as a result of competing regulation between Ca2+ mobilization and actin reorganization.

Bitter tastant quinine modulates glucagon-like peptide-1 exocytosis from clonal GLUTag enteroendocrine L cells via actin reorganization.

Enteroendocrine L cells in the gastrointestinal tract secrete glucagon-like peptide-1 (GLP-1), which plays an important role in glucose homeostasis. Here we investigated the effect of bitter tastant quinine on GLP-1 secretion using clonal GLUTag mouse enteroendocrine L cells. We found that GLUTag cells expressed putative quinine receptors at mRNA levels. Although application of quinine resulted in an increase of intracellular Ca2+ levels, which was mediated by Ca2+ release from the endoplasmic reticulum and Ca2+ influx through voltage-sensitive Ca2+ channels, quinine had little effect on GLP-1 secretion. Total internal reflection fluorescence microscopy and immunocytochemistry revealed that GLP-1-containing vesicles remained unfused with the plasma membrane and facilitated actin polymerization beneath the plasma membrane after application of quinine, respectively. Interestingly, application of forskolin together with quinine induced GLP-1 exocytosis from the cells. These results suggest that quinine does not induce GLP-1 secretion because it facilitates Ca2+ increase and actin reorganization but not cAMP increase, and both Ca2+ and cAMP are essential for GLP-1 secretion.

Impact of rehabilitation dose on body mass index change in older acute patients with stroke: a retrospective observational study.

Background: It is established that a low body mass index (BMI) correlates with a diminished home discharge rate and a decline in activities of daily living (ADL) capacity among elderly stroke patients. Nevertheless, there exists a paucity of knowledge regarding strategies to mitigate BMI reduction during the acute phase. This investigation seeks to elucidate the impact of rehabilitation dose, as determined by both physical and occupational therapy, on BMI alterations, positing that a heightened rehabilitation dose could thwart BMI decline. Methods: This retrospective, observational study was conducted in the stroke unit of a university hospital. Enrollees comprised individuals aged ≥65 years, hospitalized for stroke, and subsequently relocated to rehabilitation facilities between January 2019 and November 2020. The percentage change in BMI (%ΔBMI) was calculated based on BMI values at admission and discharge. Multivariate multiple regression analysis was employed to ascertain the influence of rehabilitation dose on %ΔBMI. Results: A total of 187 patients were included in the analysis, of whom 94% experienced a reduction in BMI during acute hospitalization. Following adjustment for sociodemographic and clinical factors, multivariable analyzes revealed a positive association between rehabilitation dose and %ΔBMI (ß = 0.338, p < 0.001). Conclusion: The findings of this study suggest that, in the context of acute stroke treatment, an augmented rehabilitation dose is associated with a diminished decrease in BMI.

Association between eating behavior and the immediate neural activity caused by viewing food images presented in and out of awareness: A magnetoencephalography study.

Obesity is a serious health problem in modern society. Considering the fact that the outcomes of treatments targeting appetitive behavior are suboptimal, one potential reason proposed for these poor outcomes is that appetitive behavior is driven more by unconscious decision-making processes than by the conscious ones targeted by traditional behavioral treatments. In this study, we aimed to investigate both the conscious and unconscious decision-making processes related to eating behavior, and to examine whether an interaction related to eating behavior exists between conscious and unconscious neural processes. The study was conducted on healthy male volunteers who viewed pictures of food and non-food items presented both above and below the awareness threshold. The oscillatory brain activity affected by viewing the pictures was assessed by magnetoencephalography. A visual backward masking procedure was used to present the pictures out of awareness. Neural activity corresponding to the interactions between sessions (i.e., food or non-food) and conditions (i.e., visible or invisible) was observed in left Brodmann's areas 45 and 47 in the high-gamma (60-200 Hz) frequency range. The interactions were associated with eating behavior indices such as emotional eating and cognitive restraint, suggesting that conscious and unconscious neural processes are differently involved in eating behavior. These findings provide valuable clues for devising methods to assess conscious and unconscious appetite regulation in individuals with normal or abnormal eating behavior.

Development of a red fluorescent protein-based cGMP indicator applicable for live-cell imaging.

Cyclic guanosine 3', 5'-monophosphate (cGMP) is a second messenger that regulates a variety of physiological processes. Here, we develop a red fluorescent protein-based cGMP indicator, "Red cGull". The fluorescence intensity of Red cGull increase more than sixfold in response to cGMP. The features of this indicator include an EC50 of 0.33 µM for cGMP, an excitation and emission peak at 567 nm and 591 nm, respectively. Live-cell imaging analysis reveal the utility of Red cGull for dual-colour imaging and its ability to be used in conjunction with optogenetics tools. Using enteroendocrine cell lines, Red cGull detects an increase in cGMP following the application of L-arginine. An increase in intracellular cGMP is found to be inhibited by Ca2+, and L-arginine-mediated hormone secretion is not potentiated. We propose that Red cGull will facilitate future research in cell signalling in relation to cGMP and its interplay with other signalling molecules.

Neural correlates of the improvement of cognitive performance resulting from enhanced sense of competence: A magnetoencephalography study.

The alterations in neural activity related to the improvement of cognitive performance, which would be leading to better academic performance, remain poorly understood. In the present study, we assessed neural activity related to the improvement of task performance resulting from academic rewards. Twenty healthy male volunteers participated in this study. All participants performed four sessions of a 1-back-Stroop task under both target and control conditions. An image indicating that the task performance of each participant was above average and categorized as being at almost the highest level was presented immediately after each session under the target condition, whereas a control image did not indicate task performance. Neural activity during the 1-back-Stroop task was recorded by magnetoencephalography. The correction rate of the 1-back-Stroop task in the final session relative to that in the first under the target condition was increased compared with the control condition. Correlation analysis revealed that the decreases in alpha band power in right Brodmann's area (BA) 47 and left BA 7 were positively associated with the increased correction rate caused by the target condition. These findings are expected to contribute to a better understanding of the neural mechanisms underlying the improvement of cognitive performance.

Neural effects of acute stress on appetite: A magnetoencephalography study.

Stress is prevalent in modern society and can affect human health through its effects on appetite. Therefore, in the present study, we aimed to clarify the neural mechanisms by which acute stress affects appetite in healthy, non-obese males during fasting. In total, 22 volunteers participated in two experiments (stress and control conditions) on different days. The participants performed a stress-inducing speech-and-mental-arithmetic task under both conditions, and then viewed images of food, during which, their neural activity was recorded using magnetoencephalography (MEG). In the stress condition, the participants were told to perform the speech-and-mental-arithmetic task again subsequently to viewing the food images; however, another speech-and-mental-arithmetic task was not performed actually. Subjective levels of stress and appetite were then assessed using a visual analog scale. Electrocardiography was performed to assess the index of heart rate variability reflecting sympathetic nerve activity. The findings showed that subjective levels of stress and sympathetic nerve activity were increased in the MEG session in the stress condition, whereas appetite gradually increased in the MEG session only in the control condition. The decrease in alpha band power in the frontal pole caused by viewing the food images was greater in the stress condition than in the control condition. These findings suggest that acute stress can suppress the increase of appetite, and this suppression is associated with the frontal pole. The results of the present study may provide valuable clues to gain a further understanding of the neural mechanisms by which acute stress affects appetite. However, since the stress examined in the present study was related to the expectation of forthcoming stressful event, our present findings may not be generalized to the stress unrelated to the expectation of forthcoming stressful event.

Effects of noninvasive ventilation on the coordination between breathing and swallowing in patients with chronic obstructive pulmonary disease.

Purpose: As shown in our previous study, inspiration after swallowing (SW-I) increases during the bi-level positive airway pressure ventilation (BiPAP) in healthy subjects because swallowing-associated non-inspiratory flow (SNIF) triggers inspiratory support, while SW-I during continuous positive pressure ventilation (CPAP) is rare. In the present study, we evaluated the coordination between breathing and swallowing during spontaneous breathing, BiPAP, and CPAP in patients with chronic obstructive pulmonary disease (COPD). Patients and methods: This study is a prospective intervention study at the Hoshigaoka Medical Center (November 01, 2015-April 30, 2018). We simultaneously recorded the respiratory flow, laryngeal motion, and swallowing sounds during saliva swallowing in patients with COPD. We estimated the respiratory phase after swallowing, frequency of SNIF, the duration of the respiratory pause during swallowing, and timing of swallowing in the respiratory cycle and compared these parameters among control, CPAP, and BiPAP conditions. Results: The expiration after swallowing (SW-E) frequency was associated with the occurrence of SNIF (p<0.01), pause duration ≤0.8 s (p<0.01), and timing of swallowing at the intermediate respiratory phase (50-80% of the respiratory cycle from the onset of inspiration) (p<0.01). In particular, the occurrence of SNIF most substantially affected the SW-E frequency. The SW-I frequencies under the control, CPAP, and BiPAP conditions were 35.0%, 3.0%, and 37.7%, respectively. The pause durations were shorter during CPAP and BiPAP than under the control condition (p<0.01). During CPAP, the occurrence rates of SW-E. Residual denotes the percentage difference between observed and expected values (residual =10.8: p<0.01) and SNIF (residual =9.1: p<0.01) were significantly increased, and timing of swallowing shifted toward the intermediate respiratory phase (residual=3.5: p<0.01). Conclusion: CPAP decreases the SW-I frequency, increases the SNIF occurrence, and normalizes the timing of swallowing, all of which suggest that CPAP alleviates the risk of aspiration in patients with COPD.

Neural effects of hand-grip-activity induced fatigue sensation on appetite: a magnetoencephalography study.

It has been reported that physical activity not only increases energy expenditure, but also affects appetite. However, little remains known about the effects of physical activity-induced fatigue sensation on appetite. In the present study, classical conditioning related to fatigue sensation was used to dissociate fatigue sensation from physical activity. The participants were 20 healthy male volunteers. After overnight fasting, on day 1, the participants performed hand-grip task trials for 10 min with listening to a sound. The next day, they viewed food images with (target task) and without (control task) listening to the sound identical to that used on day 1, and their neural activity during the tasks were recorded using magnetoencephalography. The subjective levels of appetite and fatigue sensation were assessed using a visual analog scale. The subjective level of fatigue increased and that of appetite for fatty foods showed a tendency toward increase in the target task while the subjective level of fatigue and that of appetite for fatty foods were not altered in the control task. In the target task, the decrease of theta (4-8 Hz) band power in the supplementary motor area (SMA), which was observed in the control task, was suppressed, and the suppression was positively correlated with appetite for fatty foods, suggesting hand grip activity-induced fatigue sensation may increase the appetite for fatty food; this increase could be related to neural activity in the SMA. These findings are expected to contribute to the understanding of the neural mechanisms of appetite in relation to fatigue.