The absence of thioredoxin-interacting protein in alveolar cells exacerbates asthma during obesity.

Obesity is associated with an increased incidence of asthma. However, the mechanisms underlying this association are not fully understood. In this study, we investigated the role of thioredoxin-interacting protein (TXNIP) in obesity-induced asthma. Asthma was induced by intranasal injection of a protease from Aspergillus oryzae in normal diet (ND)- or high fat diet (HFD)-fed mice to investigate the symptoms. We measured TXNIP expression in the lungs of patients with asthma and in ND or HFD asthmatic mice. To explore the role of TXNIP in asthma pathogenesis, we induced asthma in the same manner in alveolar type 2 cell-specific TXNIP deficient (TXNIPCre) mice. In addition, the expression levels of pro-inflammatory cytokines were compared based on TXNIP gene expression in A549 cells stimulated with recombinant human tumor necrosis factor alpha. Compared to ND-fed mice, HFD-fed mice had elevated levels of free fatty acids and adipokines, resulting in high reactive oxygen species levels and more severe asthma symptoms. TXNIP expression was increased in both, asthmatic patients and HFD asthmatic mice. However, in experiments using TXNIPCre mice, despite being TXNIP deficient, TXNIPCre mice exhibited exacerbated asthma symptoms. Consistent with this, in vitro studies showed highest expression levels of pro-inflammatory cytokines in TXNIP-silenced cells. Overall, our findings suggest that increased TXNIP levels in obesity-induced asthma is compensatory to protect against inflammatory responses.

Green tea extract suppresses airway inflammation via oxidative stress-driven MAPKs/MMP-9 signaling in asthmatic mice and human airway epithelial cells.

Introduction: The anti-inflammatory effect of green tea extract (GTE) has been confirmed in asthmatic mice, however, the pharmacological mechanism is not fully elucidated. Methods: To investigate the therapeutic efficacy of GTE in asthma and identify specific pathways, murine model of allergic asthma was established by ovalbumin (OVA) sensitization and the challenge for 4 weeks, with oral treatment using GTE and dexamethasone (DEX). Inflammatory cell counts, cytokines, OVA-specific IgE, airway hyperreactivity, and antioxidant markers in the lung were evaluated. Also, pulmonary histopathological analysis and western blotting were performed. In vitro, we established the model by stimulating the human airway epithelial cell line NCI-H292 using lipopolysaccharide, and treating with GTE and mitogen-activated protein kinases (MAPKs) inhibitors. Results: The GTE100 and GTE400 groups showed a decrease in airway hyperresponsiveness and the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) compared to the OVA group. GTE treatment also reduced interleukin (IL)-13, IL-5, and IL-4 levels in the BALF, and OVA-specific immunoglobulin E levels in the serum compared to those in the OVA group. GTE treatment decreased OVA-induced mucus secretion and airway inflammation. In addition, GTE suppressed the oxidative stress, and phosphorylation of MAPKs, which generally occurs after exposure to OVA. GTE administration also reduced matrix metalloproteinase-9 activity and protein levels. Conclusion: GTE effectively inhibited asthmatic respiratory inflammation and mucus hyperproduction induced by OVA inhalation. These results suggest that GTE has the potential to be used for the treatment of asthma.

Early functional factors for predicting outcome of independence in daily living after stroke: a decision tree analysis.

OBJECTIVE: This study aimed to investigate the predictive functional factors influencing the acquisition of basic activities of daily living performance abilities during the early stages of stroke rehabilitation using classification and regression analysis trees. METHODS: The clinical data of 289 stroke patients who underwent rehabilitation during hospitalization (164 males; mean age: 62.2 ± 13.9 years) were retrospectively collected and analysed. The follow-up period between admission and discharge was approximately 6 weeks. Medical records, including demographic characteristics and various functional assessments with item scores, were extracted. The modified Barthel Index on discharge served as the target outcome for analysis. A "good outcome" was defined as a modified Barthel Index score ≥ 75 on discharge, while a modified Barthel Index score < 75 was classified as a "poor outcome." RESULTS: Two classification and regression analysis tree models were developed. The first model, predicting activities of daily living outcomes based on early motor functions, achieved an accuracy of 92.4%. Among patients with a "good outcome", 70.9% exhibited (i) ≥ 4 points in the "sitting-to-standing" category in the motor assessment scale and (ii) 32 points on the Berg Balance Scale score. The second model, predicting activities of daily living outcome based on early cognitive functions, achieved an accuracy of 82.7%. Within the "poor outcome" group, 52.2% had (i) ≤ 21 points in the "visuomotor organization" category of Lowenstein Occupational Therapy Cognitive Assessment, (ii) ≤ 1 point in the "time orientation" category of the Mini Mental State Examination. CONCLUSION: The ability to perform "sitting-to-standing" and visuomotor organization functions at the beginning of rehabilitation emerged as the most significant predictors for achieving successful basic activities of daily living on discharge after stroke.

Comparison of biomechanical parameters in lower limb joints of stroke patients according to conventional evaluation scores during level walking.

Objective: Patients with chronic stroke capable of independent gait were classified into functional ambulation category (FAC) 4 or 5, and the kinetic and kinematic data on their lower limb joints on the affected and unaffected sides were compared with that of healthy individuals. Finally, the qualitative changes in the gait of patients with stroke were investigated based on the differences in FAC scores. Methods: Twelve healthy participants and 19 patients with stroke capable of independent gait were included. The three-dimensional (3D) motion analysis and conventional assessment were conducted for all patients with stroke. Results: The FAC 5 group exhibited a larger range of motion (ROM) than the FAC 4 group in knee and hip joints on the affected side and only in the hip on the unaffected side. In the FAC 5 group, ROM differences in the healthy group on either the affected or unaffected side were absent. The peak of the hip flexion moment on the affected side in both the FAC 4 and 5 groups was smaller than that in the healthy group and in the FAC 4 group on the unaffected side. The absorption power minimum on the affected side was smaller only in the FAC 4 group than that in the healthy group and was larger in the FAC 5 group than that in the FAC 4 group. On the unaffected side, the absorption power minimum was smaller only in the FAC 4 group than that in the healthy group. Conclusion: Functional differences in gait were found in patients classified based on conventional evaluation capable of independent gait after post-stroke rehabilitation. Patients may not exhibit complete recovery in the kinetic indices even if they are judged to be normal in the conventional evaluation, and the kinematic gait indices indicate recovery. Evaluating kinetic indices in addition to kinematic indices is necessary, and joint power may be an especially useful index.

Comparative study of young-old and old-old people using functional evaluation, gait characteristics, and cardiopulmonary metabolic energy consumption.

BACKGROUND: Walking is an important factor in daily life. Among older adults, gait function declines with age. In contrast to the many studies revealing gait differences between young adults and older adults, few studies have further divided older adults into groups. The purpose of this study was to subdivide an older adult population by age to identify age-related differences in functional evaluation, gait characteristics and cardiopulmonary metabolic energy consumption while walking. METHODS: This was a cross-sectional study of 62 old adult participants who were classified into two age groups of 31 participants each as follows: young-old (65-74 years) and old-old (75-84 years) group. Physical functions, activities of daily living, mood state, cognitive function, quality of life, and fall efficacy were evaluated using the Short Physical Performance Battery (SPPB), Four-square Step Test (FSST), Timed Up and Go Test (TUG), Korean Version of the Modified Barthel Index, Geriatric Depression Scale (GDS), Korean Mini-mental State Examination, EuroQol-5 Dimensions (EQ-5D) questionnaire, and the Korean version of the Fall Efficacy Scale. A three-dimensional motion capture system (Kestrel Digital RealTime System®; Motion Analysis Corporation, Santa Rosa, CA, USA) and two force plates (TF-4060-B; Tec Gihan, Kyoto, Japan) were used to investigate spatiotemporal gait parameters (velocity, cadence, stride length, stride width, step length, single support, stance phase, and swing phase), kinematic variables (hip, knee, and ankle joint angles), and kinetic variables (hip, knee, and ankle joint moment and power) of gait. A portable cardiopulmonary metabolic system (K5; Cosmed, Rome, Italy) was used to measure cardiopulmonary energy consumption. RESULTS: The old-old group showed significantly lower SPPB, FSST, TUG, GDS-SF, and EQ-5D scores (p < 0.05). Among spatiotemporal gait parameters, velocity, stride length, and step length were significantly lower in the old-old group than in the young-old group (p < 0.05). Among the kinematic variables, the knee joint flexion angles during initial contact and terminal swing phase were significantly higher in the old-old than the young-old group (P < 0.05). The old-old group also showed a significantly lower ankle joint plantarflexion angle during the pre- and initial swing phases (P < 0.05). Among the kinetic variables, the hip joint flexion moment and knee joint absorption power in the pre-swing phase were significantly lower in the old-old than the young-old group (P < 0.05). CONCLUSION: This study demonstrated that participants 75-84 years of age had less functional gaits than their young-old counterparts (65-74 years old). As the walking pace of old-old people diminishes, driving strength to move ahead and pressure on the knee joint also tend to decrease together with stride length. These differences in gait characteristics according to age among older adults could improve our understanding of how aging causes variations in gait that increase the risk of falls. Older adults of different ages may require customized intervention plans, such as gait training methods, to prevent age-related falls. TRIAL REGISTRATION: Clinical trials registration information: ClinicalTrials.gov Identifier: NCT04723927 (26/01/2021).