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Journal of Translational Medicine Jun 2024Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV)...
BACKGROUND
Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV) infection, suggesting the involvement of the gut-to-lung axis in a host's response to IAV. IAV primarily destroys airway epithelium tight junctions (TJs) and consequently causes acute respiratory disease syndrome. It is known that GM and their metabolism produce an anti-influenza effect, but their role in IAV-induced airway epithelial integrity remains unknown.
METHODS
A mouse model of IAV infection was established. GM were analyzed using 16S rRNA gene sequencing, and short-chain fatty acids (SCFAs) levels were measured. GM depletion and fecal microbiota transplantation (FMT) were conducted to validate the role of GM in IAV infection. A pair-feeding experiment was conducted to reveal whether IAV-induced GM dysbiosis is attributed to impaired food intake. Furthermore, human bronchial epithelial (HBE) cells were cocultured with IAV in the presence or absence of acetate. TJs function was analyzed by paracellular permeability and transepithelial electronic resistance (TEER). The mechanism of how acetate affects TJs integrity was evaluated in HBE cells transfected with G protein-coupled receptor 43 (GPR43) short hairpin RNA (shRNA).
RESULTS
IAV-infected mice exhibited lower relative abundance of acetate-producing bacteria (Bacteroides, Bifidobacterium, and Akkermansia) and decreased acetate levels in gut and serum. These changes were partly caused by a decrease in food consumption (due to anorexia). GM depletion exacerbated and FMT restored IAV-induced lung inflammatory injury. IAV infection suppressed expressions of TJs (occludin, ZO-1) leading to disrupted airway epithelial barrier function as evidenced by decreased TEER and increased permeability. Acetate pretreatment activated GPR43, partially restored IAV-induced airway epithelial barrier function, and reduced inflammatory cytokines levels (TNF-α, IL-6, and IL-1β). Such protective effects of acetate were absent in HBE cells transfected with GPR43 shRNA. Acetate and GPR43 improved TJs in an AMP-activated protein kinase (AMPK)-dependent manner.
CONCLUSION
Collectively, our results demonstrated that GM protected airway TJs by modulating GPR43-AMPK signaling in IAV-induced lung injury. Therefore, improving GM dysbiosis may be a potential therapeutic target for patients with IAV infection.
Topics: Animals; Tight Junctions; Gastrointestinal Microbiome; Acetates; Humans; Lung Injury; Orthomyxoviridae Infections; Mice, Inbred C57BL; Influenza A virus; Fecal Microbiota Transplantation; Receptors, G-Protein-Coupled; Mice; Epithelial Cells; Dysbiosis; Fatty Acids, Volatile
PubMed: 38879538
DOI: 10.1186/s12967-024-05376-4 -
Scientific Reports Jun 2024Myxovirus resistance (Mx) proteins are products of interferon stimulated genes (ISGs) and Mx proteins of different species have been reported to mediate antiviral...
Myxovirus resistance (Mx) proteins are products of interferon stimulated genes (ISGs) and Mx proteins of different species have been reported to mediate antiviral activity against a number of viruses, including influenza A viruses (IAV). Ferrets are widely considered to represent the 'gold standard' small animal model for studying pathogenesis and immunity to human IAV infections, however little is known regarding the antiviral activity of ferret Mx proteins. Herein, we report induction of ferret (f)Mx1/2 in a ferret lung cell line and in airway tissues from IAV-infected ferrets, noting that fMx1 was induced to higher levels that fMx2 both in vitro and in vivo. Overexpression confirmed cytoplasmic expression of fMx1 as well as its ability to inhibit infection and replication of IAV, noting that this antiviral effect of fMx1was modest when compared to cells overexpressing either human MxA or mouse Mx1. Together, these studies provide the first insights regarding the role of fMx1 in cell innate antiviral immunity to influenza viruses. Understanding similarities and differences in the antiviral activities of human and ferret ISGs provides critical context for evaluating results when studying human IAV infections in the ferret model.
Topics: Animals; Myxovirus Resistance Proteins; Ferrets; Influenza A virus; Humans; Orthomyxoviridae Infections; Virus Replication; Antiviral Agents; Cell Line; Mice; Immunity, Innate; Lung
PubMed: 38866913
DOI: 10.1038/s41598-024-63314-2 -
Frontiers in Veterinary Science 2024To compare the cardiopulmonary effects of apneustic anesthesia ventilation (AAV) and conventional mechanical ventilation (CMV) in anesthetized pigs and to describe a new...
OBJECTIVE
To compare the cardiopulmonary effects of apneustic anesthesia ventilation (AAV) and conventional mechanical ventilation (CMV) in anesthetized pigs and to describe a new mode of ventilation for anesthetized veterinary species.
STUDY DESIGN
Randomized, crossover design without washout.
ANIMALS
Twelve healthy, female white Landrace pigs.
METHODS
Following ketamine-midazolam premedication and anesthetic induction with propofol, the trachea was intubated, and each pig was positioned in dorsal recumbency. Anesthesia was maintained with propofol and sufentanil infusions. Pigs were instrumented and their lungs were sequentially ventilated with each mode, in random order, for 1 h according to predefined criteria [fraction of inspired oxygen (FiO) = 0.21, 10 mL kg tidal volume (V), and arterial carbon dioxide tension (PaCO) within 40-45 mmHg]. Cardiopulmonary data were collected at baseline, 30 and 60 min. In 8 pigs, thoracic computed tomography (CT) was performed following the 60 min time point for each mode of ventilation and images were analyzed to quantify lung aeration. The effects of ventilation mode, time, and order were analyzed using repeated measures ANOVA. Paired -tests were used to compare lung aeration between modes. Significance was defined as < 0.05.
RESULTS
Data from 12 pigs were analyzed. A significant effect of mode was found for heart rate, mean arterial pressure (MAP), pulmonary artery occlusion pressure, cardiac index (CI), stroke volume index, systemic vascular resistance, pulmonary vascular resistance, oxygen delivery index (DOI), oxygen extraction ratio (OER), V, arterial oxygen tension, arterial hemoglobin saturation, PaCO, end-tidal carbon dioxide tension, alveolar dead space (V/V), venous admixture ( ), mean airway pressure, and dynamic compliance index (CI). Order effects were also observed for some cardiovascular and respiratory variables. For the eight pigs that underwent thoracic CT, AAV resulted in significantly larger proportions of normally and hyperaerated lung while CMV resulted in larger proportions of hypoaerated and atelectatic lung.
CONCLUSIONS
In dorsally recumbent anesthetized pigs, ventilated with FiO = 0.21, both modes of ventilation supported adequate oxygenation while AAV resulted in higher CI, and lower V/V and , compared with CMV. AAV was also associated with lower MAP, CI, and DOI and higher OER compared with CMV. Further investigation of AAV in anesthetized animals is warranted.
PubMed: 38855412
DOI: 10.3389/fvets.2024.1378617 -
Cureus May 2024Subglottic stenosis (SGS) can be asymptomatic in cases with slow-growing granulomas. In this study, we report a case of SGS discovered during tracheal intubation for...
Subglottic stenosis (SGS) can be asymptomatic in cases with slow-growing granulomas. In this study, we report a case of SGS discovered during tracheal intubation for anesthesia induction. A 74-year-old woman was scheduled for surgery under general anesthesia for a left humeral fracture. Resistance was observed when the tracheal tube passed through the glottis, stopping the tube from advancing. We placed a laryngeal mask (LMA) to secure her airway and examined it using a bronchial fiber to detect circumferential stenosis of the subglottis due to granulation. The airway was secured using an LMA instead of intubation, and the patient was successfully managed under anesthesia. Asymptomatic SGS is difficult to detect preoperatively, and anesthesiologists may encounter unexpected intubation issues. LMA is an important tool for an effective strategy to manage intubation difficulties.
PubMed: 38832207
DOI: 10.7759/cureus.59543 -
Frontiers in Pediatrics 2024Although neonatal breathing patterns vary after perinatal asphyxia, whether they change during therapeutic hypothermia (TH) remains unclear. We characterized breathing...
INTRODUCTION
Although neonatal breathing patterns vary after perinatal asphyxia, whether they change during therapeutic hypothermia (TH) remains unclear. We characterized breathing patterns in infants during TH for hypoxic-ischemic encephalopathy (HIE) and normothermia after rewarming.
METHODS
In seventeen spontaneously breathing infants receiving TH for HIE and in three who did not receive TH, we analyzed respiratory flow and esophageal pressure tracings for respiratory timing variables, pulmonary mechanics and respiratory effort. Breaths were classified as braked (inspiratory:expiratory ratio ≥1.5) and unbraked (<1.5).
RESULTS
According to the expiratory flow shape braked breaths were chategorized into early peak expiratory flow, late peak expiratory flow, slow flow, and post-inspiratory hold flow (PiHF). The most braked breaths had lower rates, larger tidal volume but lower minute ventilation, inspiratory airway resistance and respiratory effort, except for the PiHF, which had higher resistance and respiratory effort. The braked pattern predominated during TH, but not during normothermia or in the uncooled infants.
CONCLUSIONS
We speculate that during TH for HIE low respiratory rates favor neonatal braked breathing to preserve lung volume. Given the generally low respiratory effort, it seems reasonable to leave spontaneous breathing unassisted. However, if the PiHF pattern predominates, ventilatory support may be required.
PubMed: 38832000
DOI: 10.3389/fped.2024.1383689 -
International Journal of Chronic... 2024To develop a novel method for calculating small airway resistance using computational fluid dynamics (CFD) based on CT data and evaluate its value to identify COPD.
PURPOSE
To develop a novel method for calculating small airway resistance using computational fluid dynamics (CFD) based on CT data and evaluate its value to identify COPD.
PATIENTS AND METHODS
24 subjects who underwent chest CT scans and pulmonary function tests between August 2020 and December 2020 were enrolled retrospectively. Subjects were divided into three groups: normal (10), high-risk (6), and COPD (8). The airway from the trachea down to the sixth generation of bronchioles was reconstructed by a 3D slicer. The small airway resistance (R) and R as a percentage of total airway resistance (R%) were calculated by CFD combined with airway resistance and FEV measured by pulmonary function test. A correlation analysis was conducted between R and pulmonary function parameters, including FEV/FVC, FEV% predicted, MEF50% predicted, MEF75% predicted and MMEF75/25% predicted.
RESULTS
The R and R% were significantly different among the three groups (p<0.05) and related to FEV/FVC (r = -0.70, p < 0.001; r = -0.67, p < 0.001), FEV% predicted (r = -0.60, p = 0.002; r = -0.57, p = 0.004), MEF50% predicted (r = -0.64, p = 0.001; r = -0.64, p = 0.001), MEF75% predicted (r = -0.71, p < 0.001; r = -0.60, p = 0.002) and MMEF 75/25% predicted (r = -0.64, p = 0.001; r = -0.64, p = 0.001).
CONCLUSION
Airway CFD is a valuable method for estimating the small airway resistance, where the derived R will aid in the early diagnosis of COPD.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Airway Resistance; Male; Retrospective Studies; Female; Middle Aged; Aged; Forced Expiratory Volume; Predictive Value of Tests; Lung; Hydrodynamics; Tomography, X-Ray Computed; Vital Capacity; Computer Simulation; Radiographic Image Interpretation, Computer-Assisted; Respiratory Function Tests
PubMed: 38826698
DOI: 10.2147/COPD.S456878 -
Frontiers in Neurology 2024Current literature extensively covers the use of sphenopalatine ganglion stimulation (SPGs) in treating a broad spectrum of medical conditions, such as allergic...
BACKGROUND
Current literature extensively covers the use of sphenopalatine ganglion stimulation (SPGs) in treating a broad spectrum of medical conditions, such as allergic rhinitis, cluster headaches, and strokes. Nevertheless, a discernible gap in the systematic organization and analysis of these studies is evident. This paper aims to bridge this gap by conducting a comprehensive review and analysis of existing literature on SPGs across various medical conditions.
METHODS
This study meticulously constructed a comprehensive database through systematic computerized searches conducted on PubMed, Embase, CNKI, Wanfang, VIP, and CBM up to May 2022. The inclusion criteria encompassed randomized controlled trials (RCTs) published in either Chinese or English, focusing on the therapeutic applications of SPGs for various medical conditions. Both qualitative and quantitative outcome indicators were considered eligible for inclusion.
RESULTS
This comprehensive study reviewed 36 publications, comprising 10 high-quality, 23 medium-quality, and three low-quality articles. The study investigated various diseases, including allergic rhinitis (AR), ischemic strokes (IS), cluster headache (CH), primary trigeminal neuralgia (PTN), pediatric chronic secretory otitis (PCSO), refractory facial paralysis (RFP), chronic tension-type headache (CTTH), as well as the analysis of low-frequency sphenopalatine ganglion stimulation (LF-SPGs) in chronic cluster headache (CCH) and the impact of SPGs on Normal nasal cavity function (NNCF). SPGs demonstrate efficacy in the treatment of AR. Regarding the improvement of rhinoconjunctivitis quality of life questionnaire (RQLQ) scores, SPGs are considered the optimal intervention according to the SUCRA ranking. Concerning the improvement in Total Nasal Symptom Score (TNSS), Conventional Acupuncture Combined with Tradiational Chinese Medicine (CA-TCM) holds a significant advantage in the SUCRA ranking and is deemed the best intervention. In terms of increasing Effective Rate (ER), SPGs outperformed both conventional acupuncture (CA) and Western Medicine (WM; < 0.05). In the context of SPGs treatment for IS, the results indicate a significant improvement in the 3-month outcomes, as evaluated by the modified Rankin Scale (mRS) in the context of Cerebral Cortical Infarction (CCI; < 0.05). In the treatment of CH with SPGs, the treatment has been shown to have a statistically significant effect on the relief and disappearance of headaches ( < 0.05). The impact of SPGs on NNCF reveals statistically significant improvements ( < 0.05) in nasal airway resistance (NAR), nasal cavity volume (NCV), exhaled nitric oxide (eNO), substance P (SP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY). SPGs treatments for PCSO, RFP, and CTTH, when compared to control groups, yielded statistically significant results ( < 0.05).
CONCLUSION
SPGs demonstrate significant effectiveness in the treatment of AR, IS, and CH. Effective management of CCH may require addressing both autonomic dysregulation and deeper neural pathways. However, additional high-quality research is essential to clarify its effects on NNCF, PTN, PCSO, RFP, and CTTH.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier CRD42021252073, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=312429.
PubMed: 38813242
DOI: 10.3389/fneur.2024.1352145 -
Nature and Science of Sleep 2024Obstructive sleep apnea (OSA) is a prevalent sleep breathing disorder characterized by intermittent hypoxia (IH), with continuous positive airway pressure (CPAP) as its...
BACKGROUND
Obstructive sleep apnea (OSA) is a prevalent sleep breathing disorder characterized by intermittent hypoxia (IH), with continuous positive airway pressure (CPAP) as its standard treatment. However, the effects of intermittent hypoxia/reoxygenation (IH/R) on weight regulation in obesity and its underlying mechanism remain unclear. Gut microbiota has gained attention for its strong association with various diseases. This study aims to explore the combined influence of IH and obesity on gut microbiota and to investigate the impact of reoxygenation on IH-induced alterations.
METHODS
Diet-induced obese (DIO) rats were created by 8-week high-fat diet (HFD) feeding and randomly assigned into three groups (n=15 per group): normoxia (NM), IH (6% O, 30 cycles/h, 8 h/day, 4 weeks), or hypoxia/reoxygenation (HR, 2-week IH followed by 2-week reoxygenation) management. After modeling and exposure, body weight and biochemical indicators were measured, and fecal samples were collected for 16S rRNA sequencing.
RESULTS
DIO rats in the IH group showed increased weight gain (p=0.0016) and elevated systemic inflammation, including IL-6 (p=0.0070) and leptin (p=0.0004). Moreover, IH rats exhibited greater microbial diversity (p<0.0167), and significant alterations in the microbial structure (p=0.014), notably the order , accompanied by an upregulation of bile acid metabolism predicted pathway (p=0.0043). Reoxygenation not only improved IH-exacerbated obesity, systemic inflammation, leptin resistance, and sympathetic activation, but also showed the potential to restore IH-induced microbial alterations. Elevated leptin levels were associated with (p=0.0008) and (p=0.0019), while body weight was linked to (p=0.0377). Additionally, the abundance of was negatively correlated with leptin levels (p=0.0006) and weight (p=0.0339).
CONCLUSION
IH leads to gut dysbiosis and metabolic disorders, while reoxygenation therapy demonstrates a potentially protective effect by restoring gut homeostasis and mitigating inflammation. It highlights the potential benefits of CPAP in reducing metabolic risk among obese patients with OSA.
PubMed: 38812701
DOI: 10.2147/NSS.S454297 -
Scientific Reports May 2024To study the characteristics of nasal airflow in the presence of nasal cycle by computational fluid dynamics. CT scan data of a healthy Chinese individual was used to...
To study the characteristics of nasal airflow in the presence of nasal cycle by computational fluid dynamics. CT scan data of a healthy Chinese individual was used to construct a three-dimensional model of the nasal cavity to be used as simulation domain. A sinusoidal airflow velocity is set at the nasal cavity entrance to reproduce the breathing pattern of a healthy human. There was a significant difference in the cross-sectional area between the two sides of the nasal cavity. Particularly, the decongested side is characterized by a larger cross-section area, and consequently, by a larger volume with respect to the congested side. The airflow velocity, pressure, and nasal resistance were higher on the congested narrow side. The temperature regulation ability on the congested narrow side was stronger than that on the decongested wider side. During the nasal cycle, there are differences in the nasal cavity function between the congested and decongested sides. Therefore, when evaluating the impact of various factors on nasal cavity function, the nasal cycle should be considered.
Topics: Humans; Nasal Cavity; Computer Simulation; Hydrodynamics; Tomography, X-Ray Computed; Male; Adult; Respiration; Airway Resistance
PubMed: 38802510
DOI: 10.1038/s41598-024-63024-9 -
Frontiers in Pharmacology 2024Vandetanib is a small-molecule tyrosine kinase inhibitor. It exerts its therapeutic effects primarily in a range of lung cancers by inhibiting the vascular endothelial...
Vandetanib is a small-molecule tyrosine kinase inhibitor. It exerts its therapeutic effects primarily in a range of lung cancers by inhibiting the vascular endothelial growth factor receptor 2. However, it remains unclear whether vandetanib has therapeutic benefits in other lung diseases, particularly asthma. The present study investigated the pioneering use of vandetanib in the treatment of asthma. experiments including establishment of an asthma model, measurement of airway resistance measurement and histological analysis were used primarily to confirm the anticontractile and anti-inflammatory effects of vandetanib, while experiments, including measurement of muscle tension and whole-cell patch-clamp recording, were used to explore the underlying molecular mechanism. experiments in an asthmatic mouse model showed that vandetanib could significantly alleviate systemic inflammation and a range of airway pathological changes including hypersensitivity, hypersecretion and remodeling. Subsequent experiments showed that vandetanib was able to relax the precontracted rings of the mouse trachea via calcium mobilization which was regulated by specific ion channels including VDLCC, NSCC, NCX and K channels. Taken together, our study demonstrated that vandetanib has both anticontractile and anti-inflammatory properties in the treatment of asthma, which also suggests the feasibility of using vandetanib in the treatment of asthma by reducing abnormal airway contraction and systemic inflammation.
PubMed: 38799165
DOI: 10.3389/fphar.2024.1345070