Respiratory physiological mechanism of two types of equal-intensity inspiratory muscle training in stable patients with chronic obstructive pulmonary disease.

PURPOSE: This study aimed to investigate the respiratory physiological changes resulting from short-term inspiratory resistance training (R-IMT) and inspiratory threshold training (T-IMT) in patients with chronic obstructive pulmonary disease (COPD) and to compare the mechanisms of the two training methods. PATIENTS AND METHODS: A total of 75 stable patients with COPD combined with inspiratory muscle weakness were randomly allocated to three groups: R-IMT (n = 26), T-IMT (n = 24), and control (n = 25). Before and after 8 weeks of inspiratory muscle training(IMT), cardiopulmonary exercise tests were conducted to assess respiratory patterns, respiratory central drive, exercise tolerance, and ventilation efficiency. RESULTS: After 8 weeks of IMT, Inspiratory muscle strength, represented by MIP (maximum inspiratory mouth pressure) and exercise capacity increased during exercise in both IMT groups (P < 0.05). In the R-IMT group, inspiratory time (Ti) prolonged (P < 0.05), tidal volume (Vt) increased (P < 0.05), ventilation efficiency (represented by ventilation-center coupling) increased (P < 0.05) during exercise. Conversely, the T-IMT group did not exhibit any of these changes after IMT (P > 0.05). CONCLUSION: In summary, the improvement in exercise tolerance was associated with an increase in inspiratory muscle reserve in both R-IMT and T-IMT. However, only R-IMT was associated with deeper and slower breathing, as well as improved ventilation efficiency.

The orchestration of cell-cycle reentry and ribosome biogenesis network is critical for cardiac repair.

Rationale: Myocardial infarction (MI) is a severe global clinical condition with widespread prevalence. The adult mammalian heart's limited capacity to generate new cardiomyocytes (CMs) in response to injury remains a primary obstacle in developing effective therapies. Current approaches focus on inducing the proliferation of existing CMs through cell-cycle reentry. However, this method primarily elevates cyclin dependent kinase 6 (CDK6) and DNA content, lacking proper cytokinesis and resulting in the formation of dysfunctional binucleated CMs. Cytokinesis is dependent on ribosome biogenesis (Ribo-bio), a crucial process modulated by nucleolin (Ncl). Our objective was to identify a novel approach that promotes both DNA synthesis and cytokinesis. Methods: Various techniques, including RNA/protein-sequencing analysis, Ribo-Halo, Ribo-disome, flow cytometry, and cardiac-specific tumor-suppressor retinoblastoma-1 (Rb1) knockout mice, were employed to assess the series signaling of proliferation/cell-cycle reentry and Ribo-bio/cytokinesis. Echocardiography, confocal imaging, and histology were utilized to evaluate cardiac function. Results: Analysis revealed significantly elevated levels of Rb1, bur decreased levels of circASXL1 in the hearts of MI mice compared to control mice. Deletion of Rb1 induces solely cell-cycle reentry, while augmenting the Ribo-bio modulator Ncl leads to cytokinesis. Mechanically, bioinformatics and the loss/gain studies uncovered that circASXL1/CDK6/Rb1 regulates cell-cycle reentry. Moreover, Ribo-Halo, Ribo-disome and circRNA pull-down assays demonstrated that circASXL1 promotes cytokinesis through Ncl/Ribo-bio. Importantly, exosomes derived from umbilical cord mesenchymal stem cells (UMSC-Exo) had the ability to enhance cardiac function by facilitating the coordinated signaling of cell-cycle reentry and Ribo-bio/cytokinesis. These effects were attenuated by silencing circASXL1 in UMSC-Exo. Conclusion: The series signaling of circASXL1/CDK6/Rb1/cell-cycle reentry and circASXL1/Ncl/Ribo-bio/cytokinesis plays a crucial role in cardiac repair. UMSC-Exo effectively repairs infarcted myocardium by stimulating CM cell-cycle reentry and cytokinesis in a circASXL1-dependent manner. This study provides innovative therapeutic strategies targeting the circASXL1 signaling network for MI and offering potential avenues for enhanced cardiac repair.

Chaperone-mediated autophagy protects the bone formation from excessive inflammation through PI3K/AKT/GSK3ß/ß-catenin pathway.

Multiple regulatory mechanisms are in place to ensure the normal processes of bone metabolism, encompassing both bone formation and absorption. This study has identified chaperone-mediated autophagy (CMA) as a critical regulator that safeguards bone formation from the detrimental effects of excessive inflammation. By silencing LAMP2A or HSCA8, we observed a hindrance in the osteoblast differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. To further elucidate the role of LAMP2A, we generated LAMP2A gene knockdown and overexpression of mouse BMSCs (mBMSCs) using adenovirus. Our results showed that LAMP2A knockdown led to a decrease in osteogenic-specific proteins, while LAMP2A overexpression favored the osteogenesis of mBMSCs. Notably, active-ß-catenin levels were upregulated by LAMP2A overexpression. Furthermore, we found that LAMP2A overexpression effectively protected the osteogenesis of mBMSCs from TNF-α, through the PI3K/AKT/GSK3ß/ß-catenin pathway. Additionally, LAMP2A overexpression significantly inhibited osteoclast hyperactivity induced by TNF-α. Finally, in a murine bone defect model, we demonstrated that controlled release of LAMP2A overexpression adenovirus by alginate sodium capsule efficiently protected bone healing from inflammation, as confirmed by imaging and histological analyses. Collectively, our findings suggest that enhancing CMA has the potential to safeguard bone formation while mitigating hyperactivity in bone absorption.

The Bioaccessibility and Bioavailability of Pentachlorophenol in Five Animal-Derived Foods Measured by Simulated Gastrointestinal Digestion.

Pentachlorophenol (PCP) is a ubiquitous emerging persistent organic pollutant detected in the environment and foodstuffs. Despite the dietary intake of PCP being performed using surveillance data, the assessment does not consider the bioaccessibility and bioavailability of PCP. Pork, beef, pork liver, chicken and freshwater fish Ctenopharyngodon Idella-fortified by three levels of PCP were processed by RIVM and the Caco-2 cell model after steaming, boiling and pan-frying, and PCP in foods and digestive juices were detected using isotope dilution-UPLC-MS/MS. The culinary treatment and food matrix were significantly influenced (p < 0.05) in terms of the bioaccessibility and bioavailability of PCP. Pan-frying was a significant factor (p < 0.05) influencing the digestion and absorption of PCP in foods, with the following bioaccessibility: pork (81.37-90.36%), beef (72.09-83.63%), pork liver (69.11-78.07%), chicken (63.43-75.52%) and freshwater fish (60.27-72.14%). The bioavailability was as follows: pork (49.39-63.41%), beef (40.32-53.43%), pork liver (33.63-47.11%), chicken (30.63-40.83%) and freshwater fish (17.14-27.09%). Pork and beef with higher fat content were a key factor in facilitating the notable PCP bioaccessibility and bioavailability (p < 0.05). Further, the exposure of PCP to the population was significantly reduced by 42.70-98.46% after the consideration of bioaccessibility and bioavailability, with no potential health risk. It can improve the accuracy of risk assessment for PCP.

Effects of Acute Ingestion of Caffeine Capsules on Muscle Strength and Muscle Endurance: A Systematic Review and Meta-Analysis.

This study aimed to explore the effects of acute ingestion of caffeine capsules on muscle strength and muscle endurance. We searched the PubMed, Web of Science, Cochrane, Scopus, and EBSCO databases. Data were pooled using the weighted mean difference (WMD) and 95% confidence interval. Fourteen studies fulfilled the inclusion criteria. The acute ingestion of caffeine capsules significantly improved muscle strength (WMD, 7.09, p < 0.00001) and muscle endurance (WMD, 1.37; p < 0.00001), especially in males (muscle strength, WMD, 7.59, p < 0.00001; muscle endurance, WMD, 1.40, p < 0.00001). Subgroup analyses showed that ≥ 6 mg/kg body weight of caffeine (WMD, 6.35, p < 0.00001) and ingesting caffeine 45 min pre-exercise (WMD, 8.61, p < 0.00001) were more effective in improving muscle strength, with the acute ingestion of caffeine capsules having a greater effect on lower body muscle strength (WMD, 10.19, p < 0.00001). In addition, the acute ingestion of caffeine capsules had a greater effect in moderate-intensity muscle endurance tests (WMD, 1.76, p < 0.00001). An acute ingestion of caffeine capsules significantly improved muscle strength and muscle endurance in the upper body and lower body of males.

Identification of Active Components for Sports Supplements: Machine Learning-Driven Classification and Cell-Based Validation.

The identification of active components is critical for the development of sports supplements. However, high-throughput screening of active components remains a challenge. This study sought to construct prediction models to screen active components from herbal medicines via machine learning and validate the screening by using cell-based assays. The six constructed models had an accuracy of >0.88. Twelve randomly selected active components from the screening were tested for their active potency on C2C12 cells, and 11 components induced a significant increase in myotube diameters and protein synthesis. The effect and mechanism of luteolin among the 11 active components as potential sports supplements were then investigated by using immunofluorescence staining and high-content imaging analysis. It showed that luteolin increased the skeletal muscle performance via the activation of PGC-1α and MAPK signaling pathways. Thus, high-throughput prediction models can be effectively used to screen active components as sports supplements.

Xylooligosaccharides ameliorate insulin resistance by increasing Akkermansia muciniphila and improving intestinal barrier dysfunction in gestational diabetes mellitus mice.

Little is known regarding the effects of xylooligosaccharides (XOS) on insulin resistance (IR) in gestational diabetes mellitus (GDM). We aimed to investigate this issue and its mechanism. Sixty female mice were randomly allotted to 4 groups (n = 15): control, high fat diet (HFD), GDM, and GDM + XOS. The control mice were fed an AIN-93 diet, while the mice in the other groups were fed 45% HFD. After pregnancy, mice in GDM and GDM + XOS groups were intraperitoneally injected with 30 mg kg-1 streptozocin for 3 days from the first day of pregnancy. Mice in the GDM + XOS group were then fed an HFD containing 2% XOS. Fasting glucose and insulin levels were monitored. The fecal Akkermansia muciniphila (Akk. muciniphila) and Bifidobacterium were measured by qPCR. The Chiu scores were calculated from hematoxylin-eosin (HE)-stained ileal tissues. Phosphorylated Akt in the liver and occludin and ZO-1 in the intestinal tissues were determined by western blotting. XOS reduced (p < 0.05) fasting blood glucose and insulin and HOMA-IR, and increased (p < 0.05) Akt phosphorylation in the livers of GDM mice. Moreover, XOS decreased (p < 0.05) TNFα, IL-1ß, IL-15 and LPS in the serum, increased (p < 0.05) fecal Akk. muciniphila abundance, lowered (p < 0.05) Chiu's scores, and enhanced (p < 0.05) occludin and ZO-1 expression. XOS ameliorate IR by increasing Akk. muciniphila and improving intestinal barrier dysfunction in GDM mice.

Assessment of osteopontin as an early nephrotoxicity indicator in human renal proximal tubule cells and its application in evaluating lanthanum-induced nephrotoxicity.

Nephrotoxicity is a common adverse effect induced by various chemicals, necessitating the development of reliable toxicity screening models for nephrotoxicity assessment. In this study, we assessed a group of nephrotoxicity indicators derived from different toxicity pathways, including conventional endpoints and kidney tubular injury biomarkers such as clusterin (CLU), kidney injury molecule-I (KIM-1), osteopontin (OPN), and neutrophil gelatinase-associated lipocalin (NGAL), using HK-2 and induced pluripotent stem cells (iPSCs)-derived renal proximal tubular epithelial-like cells (PTLs). Among the biomarkers tested, OPN emerged as the most discerning and precise marker. The predictive potential of OPN was tested using a panel of 10 nephrotoxic and 5 non-nephrotoxic compounds. The results demonstrated that combining OPN with the half-maximal inhibitory concentration (IC50) enhanced the diagnostic accuracy in both cellular models. Additionally, PTLs cells showed superior predictive efficacy for nephrotoxicity compared to HK-2 cells in this investigation. The two cellular models were utilized to evaluate the nephrotoxicity of lanthanum. The findings indicated that lanthanum possesses nephrotoxic properties; however, the degree of nephrotoxicity was relatively low, consistent with the outcomes of in vivo experiments.