Respiratory Physiology & Neurobiology最新文献

Ticagrelor, a P2Y₁₂ receptor antagonist, has been demonstrated to induce dyspnea, which is not associated with cardiac or pulmonary alterations, or metabolic disturbances. The attribution of ticagrelor-related dyspnea to excess adenosine has been widely proposed, yet is not supported by experimental data. In this paper, we put forth a novel hypothesis that the hyperactivity of the retrotrapezoid nucleus, a group of ventral medullary neurons involved in respiratory modulation, is the underlying cause of ticagrelor-related dyspnea. This hypothesis offers a theoretical resolution to the discrepancies and controversies present in previous theories.

Asthma is a lung condition characterized by impaired respiratory function and an apparent infiltration of inflammatory cells. Chalcones are substances that have attracted considerable interest in the disciplines of pharmaceutical chemistry and drug discovery due to their diverse biochemical processes, such as antioxidant, anti-inflammatory, anticancer, antibacterial, and others, but whether they can be used in asthma treatment has yet to be investigated. This study aimed to investigate the immunomodulatory effect of 4 hydroxychalcone (4-HC) against allergic asthma in mice. In this research, we investigated how 4-HC affected asthmatic behavior, leukocyte infiltration, histopathological alterations, oxidative stress, immunoglobulin E (IgE) production, and airway inflammation. Moreover, ELISA and immunohistochemistry (IHC) were used to measure the expression of Nrf2 and GPx4. 4-HC treatment significantly decreased lung oxidative stress, inflammatory cell infiltration, and IgE levels. According to our findings, we imply that 4-HC may be utilized as an anti-asthmatic agent through the upregulation of Nrf2/GPx4 signaling pathway.

Sinusitis, a common disease of the maxillary sinus, is initially managed with saline solution and medication, resulting in the resolution of symptoms within a few days in most cases. However, Functional Endoscopic Sinus Surgeries are recommended if pharmacological treatments prove ineffective. This research aims to investigate the effects of maxillary sinus surgery on the airflow field, pressure distribution within the nasal cavity, and overall ventilation. This study utilized a three-dimensional realistic nasal cavity model constructed from CT images of a healthy adult. Virtual surgery including uncinectomy with Middle Meatal Antrostomy, two standard procedures performed during such surgeries, was performed on the model under the supervision of a clinical specialist. Two replicas representing pre- and post-operative cases were created using 3D printing for experimental purposes. Various breathing rates ranging from 3.8 to 42.6 L/min were examined through experimental and numerical simulations. To ensure the accuracy of the numerical simulations, the results were compared to measured pressure data, showing a reasonable agreement between the two. The findings demonstrate that uncinectomy and Middle Meatal Antrostomy significantly enhance the ventilation of the maxillary sinuses. Furthermore, increasing inspiratory rates leads to further improvements in ventilation. The static pressure distribution within the maxillary sinuses remains relatively uniform, except in regions close to the sinus ostium, even after surgical intervention.

Background

Acute lung injury (ALI) is a life-threatening condition characterized by excessive pulmonary inflammation, yet its precise pathophysiology remains elusive. Pyroptosis, a programmed cell death mechanism controlled by gasdermin D (GSDMD), has been linked to the etiology of ALI. This study investigated the regulatory functions of the transcription factor E-twenty-six variant gene 5 (ETV5) and GSDMD in ALI.

Methods

Lipopolysaccharide (LPS) was used to treat BEAS-2B cells (50 mmol/mL) and establish an LPS-induced mouse model of ALI (by intratracheal administration, 3 mg/kg). Protein-protein docking, immunofluorescence analysis, western blotting, real-time quantitative polymerase chain reaction, and dual-luciferase reporter gene assay were used to examine ETV5-mediated negative feedback regulation of GSDMD and its effects on pyroptosis and ALI.

Results

Our results showed that the physiological function of ETV5 was reduced by its downregulated expression, which impeded its nuclear translocation in ALI mice. Increased pyroptosis and enhanced production of inflammatory cytokines were associated with LPS-induced ALI. ETV5 overexpression in LPS-treated BEAS-2B cells decreased the expression of total and membrane-bound GSDMD, negatively regulated GSDMD, and prevented pyroptosis. The expression of inflammatory cytokines was subsequently reduced due to this inhibition, which, in turn, reduced ALI. Molecular docking analysis and dual-luciferase reporter gene assay results indicated a direct interaction between ETV5 and GSDMD, which inhibited GSDMD production.

Conclusion

Our results indicate that ETV5 inhibits pyroptosis, decreases the expression of inflammatory cytokines, and negatively regulates GSDMD expression to ameliorate ALI symptoms.

Highly trained aerobic athletes progressively use most of their breathing reserve with increased exercise intensity during whole-body exercise. Additionally, females typically present proportionally smaller lungs than males. Therefore, sex, exercise intensity, and breathing reserve use likely influence the volume and time in which respiratory parameters vary between consecutive breaths during whole-body exercise. However, breath-by-breath variability has been scarcely investigated during exercise. Accordingly, we sought to investigate breath-by-breath pulmonary ventilation (V̇_E), tidal volume ₍V_T), and respiratory frequency (f_R) variability during a maximal treadmill incremental exercise test in 17 females and 18 males highly trained professional endurance runners. The breath-by-breath variability was analyzed by root mean square of successive differences (RMSSD) within 1-minute windows. Females had lower absolute and percent predicted forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC) than males, as well as lower height-adjusted absolute FVC than males. V̇_E and V_T reserve use were similar between the sexes at peak exercise. While RMSSDV̇_E and RMSSDf_R did not change over exercise (P > 0.05), RMSSDV_T progressively decreased (P < 0.001). RMSSDV_T was negatively correlated with V_T reserve use only in males. Females showed lower RMSSDV̇_E than males during the entire exercise test (P < 0.001). At iso-V̇_E reserve use, between-sex differences in RMSSDV̇_E persisted (P = 0.003). Our findings indicate that exercise intensity decreases V_T variability in professional runners, which is linked to V_T reserve use in males but not females. Additionally, the female sex lowers V̇_E variability regardless of exercise intensity and V̇_E reserve use.

Objective

To determine if change in body position improves oxygen requirements and respiratory mechanics during the transition from total liquid ventilation (TLV) to gas ventilation.

Methods

Fourteen piglets underwent TLV, followed by a 2-hour weaning period under conventional gas ventilation. Subjects were randomized to the experimental group (Rotating – R), that was in prone position between the 10th and 30th minute of weaning, or to the static control group (Supine – S).

Results

Oxygenation index was lower in the R group at 30 minutes in prone position than that in the S group (1.9 [1.6; 2.8] vs 3.5 [3.1; 5.1], p = 0.001). This difference disappeared when subjects resumed the supine position (4.2 [3.8; 4.7] and 4.7 [3.8; 5.4], p = 0.4, for the R and S groups, respectively). The change in body position did not affect respiratory system compliance or inspiratory capacity.

Conclusion

Prone position improved oxygenation during weaning from TLV. The effect disappeared once piglets returned to the supine position.

Resting breathing and ventilatory chemoreflexes are regulated in a 24-hr manner by the endogenous circadian clock. However, it is unclear how circadian biology influences different phases of the breath-to-breath respiratory cycle which are predominantly controlled by pontomedullary regions of the brainstem. Here, we performed whole-body plethysmography during quiet wakefulness in young adult male and female mice lacking the core clock gene Brain and Muscle Arnt-like 1 (BMAL1) to determine the extent to which the molecular clock affects respiratory cycle timing and ventilatory airflow mechanics. Breath waveform analysis revealed that male BMAL1 knockout (KO) mice exhibit time of day-specific differences in inspiratory and expiratory times, total cycle length, end inspiratory pause, relaxation time, and respiratory rate compared to wild-type littermates. Notably, changes in respiratory pattern were not observed in female BMAL1 KO mice when compared to wild-type females. Additionally, BMAL1 deficiency did not disrupt overall minute ventilation or peak airflow in either sex, suggesting total ventilatory function during quiet wakefulness is preserved. Taken together, these findings indicate that genetic disruption of the circadian clock in mice elicits sex-specific changes in respiratory cycle timing.

Background

Invasive ventilation of infants born before 24 weeks of gestation is critical for survival and long-term respiratory outcomes, but currently there is a lack of evidence to guide respiratory management. We aimed to compare respiratory mechanics and gas exchange in ventilated extremely preterm infants born before and after 24 weeks of gestation.

Methods

Secondary analysis of two prospective observational cohort studies, comparing respiratory mechanics and indices of gas exchange in ventilated infants born at 22–24 weeks of gestation (N=14) compared to infants born at 25–27 weeks (N=37). The ventilation/perfusion ratio (V_A/Q), intrapulmonary shunt, alveolar dead space (V_Dalv) and adjusted alveolar surface area (S_A) were measured in infants born at the Neonatal Unit of King’s College Hospital NHS Foundation Trust, London, UK.

Results

Compared to infants of 25–27 weeks, infants of 22–24 weeks had higher median (IQR) intrapulmonary shunt [18 (4 - 29) % vs 8 (2 – 12) %, p=0.044] and higher V_Dalv [0.9 (0.6 – 1.4) vs 0.6 (0.5 – 0.7) ml/kg, p=0.036], but did not differ in V_A/Q. Compared to infants of 25–27 weeks, the infants of 22–24 weeks had a lower adjusted S_A [509 (322- 687) vs 706 (564 - 800) cm², p=0.044]. The infants in the two groups did not differ in any of the indices of respiratory mechanics.

Conclusion

Ventilated infants born before 24 completed weeks of gestation exhibit abnormal gas exchange, with higher alveolar dead space and intrapulmonary shunt and a decreased alveolar surface area compared to extreme preterms born after 24 weeks of gestation.