The association between time-restricted eating and arterial stiffness status in community-dwelling elderly Chinese individuals.

BACKGROUND AND AIMS: Emerging studies indicate that time-restricted eating (TRE) may protect against cardiovascular disease (CVD); however, studies performed in elderly adults are limited. This study aimed to analyze the association of TRE with arterial stiffness (AS) in community-dwelling elderly Chinese individuals. METHODS AND RESULTS: This cross-sectional study recruited 3487 participants aged ≥60 y from Shanghai, China. TRE was determined by calculating the end time of the last meal minus the start time of the first meal of the average day. Participants were then categorized into those with a time-restricted window lasting ≤11 h (TRE) and >11 h (non-TRE). The mean age of the sample was 71.78 ± 5.75 y, and 41.2 % were men. Having a TRE pattern was 72.2 %. In the logistic analysis, TRE was associated with borderline arterial stiffness (OR = 1.419; 95 % CI = 1.077-1.869) and elevated arterial stiffness (OR = 1.699; 95 % CI = 1.276-2.263). In a subgroup analysis, the significance remained in the group at risk of malnutrition (with borderline arterial stiffness: OR = 2.270; 95 % CI = 1.229-4.190; with elevated arterial stiffness: OR = 2.459; 95 % CI = 1.287-4.700), while in well-nourished participants, the association only remained with elevated arterial stiffness (OR = 1.530; 95 % CI = 1.107-2.115) and not with borderline arterial stiffness. CONCLUSIONS: TRE is a risk factor for both borderline and elevated arterial stiffness in community-dwelling Chinese individuals and varies by nutritional status. (Protocol code 2019-WJWXM-04-310108196508064467.).

Abnormal sleep patterns are associated with depressive symptoms in Chinese community-dwelling older adults.

OBJECTIVE: Depression is an important public health issue among older adults, often associated with their sleep-related problems. We aimed to investigate the association between sleep-related problems and depressive symptoms among Chinese community-dwelling older adults. METHODS: This cross-sectional study utilized self-reported data from 2896 participants (aged ≥60 years) from Shanghai, China. Nocturnal sleep duration and difficulty initiating sleep (DIS) symptoms were obtained through face-to-face questionnaires. Nocturnal sleep duration was categorized as 'short' (<7 h), 'normal' (7-8 h), and 'long' (>8 h). Subsequently, the 3 groups were further divided into 6 groups based on the presence of DIS, and the combined sleep behaviors were termed 'sleep patterns'. Logistic regression was conducted to assess the association of sleep variables and sleep patterns with the risk of depressive symptoms. RESULTS: Compared to the reference group, 'short sleep duration' and DIS symptoms were associated with depressive symptoms (with odds ratios (OR) of 1.50 and 1.79, respectively, with 95% confidence intervals (CI) of 1.14-1.97 and 1.39-2.31). When compared to 'normal sleep duration without DIS', both 'short sleep duration with DIS' (OR = 2.60, 95% CI: 1.81-3.72) and 'normal sleep duration with DIS' (OR = 1.60, 95% CI: 1.03-2.49) were statistically associated with depressive symptoms in adjusted regression models. CONCLUSION: Short sleep duration and DIS symptoms were found to be associated with depressive symptoms. Combining DIS symptoms with sleep duration, DIS was identified as a risk factor for elevated depressive symptoms in individuals with short and normal sleep durations. In managing depressive symptoms, it is imperative to thoroughly evaluate insomnia and nighttime sleep, which can provide valuable insights for nursing and medical policy.

Lower heart rate variability is associated with loss of muscle mass and sarcopenia in community-dwelling older Chinese adults.

BACKGROUND/PURPOSE: Autonomic nervous system (ANS) disorders may occur in skeletal muscle disease, but the link between them has not been fully established. Studying the relationship between them may yield insights into the mechanisms and treatment of disease. This study aimed to explore the association between heart rate variability (HRV), sarcopenia, and subscales of sarcopenia (muscle mass, muscle strength, and physical mobility). METHODS: 2514 community-dwelling older Chinese participants were included in this study. The Asian Working Group for Sarcopenia guidelines were used to define sarcopenia. HRV was measured by 90-s electrocardiogram RR interval data. All HRV parameters were transformed using natural logarithms. Multiple regression analysis and multivariate linear regression was performed using potential correlates. RESULTS: The overall prevalence of sarcopenia was 15.1 % (18.5 % in males and 12.6 % in females). In the logistic regression analysis model, there was a significant association between log-transformed standard deviation of RR interval (lnSDNN) (OR = 0.736, p = 0.019), log-transformed coefficient of variation of RR intervals (lnCVRR) (OR = 0.751, p = 0.020), log-transformed low-frequency power (lnLF) (OR = 0.861, p = 0.008), log-transformed high-frequency power (lnHF) (OR = 0.864, p = 0.003) and sarcopenia in the general population after adjusting for age, sex, body mass index (BMI), daily activity levels, hypertension, heart disease and cardiac drugs. In addition, in multivariate linear regression, lnSDNN (ß = 0.146, p = 0.001), lnCVRR (ß = 0.120, p = 0.010), lnLF (ß = 0.066, p = 0.002) and lnHF (ß = 0.065, p < 0.001) remained significantly positively associated with muscle mass, but there were no significant differences in grip strength and walking speed. CONCLUSIONS: Sarcopenia was independently associated with lower heart rate variability in a community-dwelling elderly Chinese population. In addition, muscle mass was positively associated with heart rate variability in the elderly.

Monitoring Strain Response of Epoxy Resin during Curing and Cooling Using an Embedded Strain Gauge.

The present work describes the monitoring system of the real-time strain response on the curing process of epoxy resin from the initial point of curing to the end, and the change in strain during temperature changes. A simple mould was designed to embed the strain gauge, thermometer, and quartz standard sample into the epoxy resin, so that the strain and the temperature were simultaneously measured and recorded. A cryogenic-grade epoxy resin was tested and the Differential Scanning Calorimetry (DSC) was used to analyse the curing process. Based on the DSC results, three curing processes were adopted to investigate their influence on strain response as well as residual strain of the epoxy resin. Moreover, impact strength of the epoxy resin with various curing temperatures were tested and the results indicate that the curing plays a crucial role on the mechanical properties. The method will find cryogenic application of epoxy adhesives and epoxy resin based composites to monitor the strain during the curing process as well as the cryogenic service.

Broad Negative Thermal Expansion Operation-Temperature Window Achieved by Adjusting Fe-Fe Magnetic Exchange Coupling in La(Fe,Si)13 Compounds.

Cubic La(Fe,Si)13-based compounds have been recently developed as promising negative thermal expansion(NTE) materials, but the narrow NTE operation-temperature window(∼110 K) restricts their actual applications. In this work, we demonstrate that the NTE operation-temperature window of LaFe(13-x)Si(x) can be significantly broadened by adjusting Fe-Fe magnetic exchange coupling as x ranges from 2.8 to 3.1. In particular, the NTE operation-temperature window of LaFe10.1Si2.9 is extended to 220 K. More attractively, the coefficients of thermal expansion of LaFe10.0Si3.0 and LaFe9.9Si3.1 are homogeneous in the NTE operation-temperature range of about 200 K, which is much valuable for the stability of fabricating devices. The further experimental characterizations combined with first-principles studies reveal that the tetragonal phase is gradually introduced into the cubic phase as the Si content increases, hence modifies the Fe-Fe interatomic distance. The reduction of the overall Fe-Fe magnetic exchange interactions contributes to the broadness of NTE operation-temperature window for LaFe(13-x)Si(x).

Zero thermal expansion in NaZn13-type La(Fe,Si)13 compounds.

A zero thermal expansion material in a pure form of NaZn13-type La(Fe,Si)13 was fabricated. Through optimizing the chemical composition, an isotropic zero thermal expansion material is achieved. The obtained materials exhibit a low expansion of |α| < 1.0 × 10(-6) K(-1) (α is the coefficient of linear thermal expansion) over a broad temperature range (15-150 K). The present study indicates that the thermal expansion behavior of the NaZn13-type La(Fe,Si)13 compounds depends mainly on the content of Si element. This new material is desirable in many fields of industry as a reliable and low-cost zero thermal expansion material.

Abnormal thermal expansion properties of cubic NaZn13-type La(Fe,Al)13 compounds.

The cubic NaZn13-type La(Fe,Al)13 compounds were synthesized, and their linear thermal expansion properties were investigated in the temperature range of 4.2-300 K. It was found that these compounds exhibit abnormal thermal expansion behavior, i.e., pronounced negative thermal expansion (NTE) or zero thermal expansion (ZTE) behavior, below the Curie temperature due to the magnetovolume effect (MVE). Moreover, in the La(Fe,Al)13 compounds, the modification of the coefficient of thermal expansion (CTE) as well as the abnormal thermal expansion (ATE) temperature-window is achieved through optimizing the proportion of Fe and Al. Typically, the average CTE of the LaFe13-xAlx compounds with x = 1.8 reaches as large as -10.47 × 10(-6) K(-1) between 100 and 225 K (ΔT = 125 K). Also, the ZTE temperature-window of the LaFe13-xAlx compounds with x = 2.5 and x = 2.7 could be broadened to 245 K (from 5 to 250 K). Besides, the magnetic properties of these compounds were measured and correlated with the abnormal thermal expansion behavior. The present results highlight the potential application of such La(Fe,Al)13 compounds with abnormal thermal expansion properties in cryogenic engineering.

Enhanced negative thermal expansion in La(1-x)Pr(x)Fe10.7Co0.8Si1.5 compounds by doping the magnetic rare-earth element praseodymium.

Experiments have been performed to enhance negative thermal expansion (NTE) in the La(Fe,Co,Si)13-based compounds by optimizing the chemical composition, i.e., proper substitution of La by magnetic element Pr. It is found that increasing the absolute value of the average coefficient of thermal expansion (CTE) in the NTE temperature region (200-300 K) attributes to enhancement of the spontaneous magnetization and its growth rate with increasing Pr content. Typically, the average CTE of La(1-x)Pr(x)Fe10.7Co0.8Si1.5 with x = 0.5 reaches as large as -38.5 × 10(-6) K(-1) between 200 and 300 K (ΔT = 100 K), which is 18.5% larger than that of x = 0. The present results highlight the potential applications of La(Fe,Co,Si)13-based compounds with a larger NTE coefficient.

Advances in the pharmacological effects and mechanisms of Nelumbo nucifera gaertn. Extract nuciferine.

ETHNOPHARMACOLOGIC RELEVANCE: The leaves of Nelumbo nucifera Gaertn. Are recorded in the earliest written documentation of traditional Chinese medicinal as "Ben Cao Gang Mu", a medicinal herb for blood clotting, dysentery and dizziness. Nuciferine, one of N. nucifera Gaertn. leaf extracts, has been shown to possess several pharmacological properties, including but not limited to ameliorating hyperlipidemia, stimulating insulin secretion, inducing vasodilation, reducing blood pressure, and demonstrating anti-arrhythmic properties. AIM OF THE STUDY: In light of the latest research findings on nuciferine, this article provides a comprehensive overview of its chemical properties, pharmacological activities, and the underlying regulatory mechanisms. It aims to serve as a dependable reference for further investigations into the pharmacological effects and mechanisms of nuciferine. MATERIALS AND METHODS: Use Google Scholar, Scifinder, PubMed, Springer, Elsevier, Wiley, Web of Science and other online database search to collect the literature on extraction, separation, structural analysis and pharmacological activity of nuciferine published before November 2023. The key words are "extraction", "isolation", "purification" and "pharmacological action" and "nuciferine". RESULTS: Nuciferine has been widely used in the treatment of ameliorating hyperlipidemia and lose weight, Nuciferine is a monomeric aporphine alkaloid extracted from the leaves of the plant Nymphaea caerulea and Nelumbo nucifera Gaertn. Nuciferine has pharmacological activities such as relaxing smooth muscles, improving hyperlipidemia, stimulating insulin secretion, vasodilation, inducing hypotension, antiarrhythmic effects, and antimicrobial and anti-HIV activities. These pharmacological properties lay a foundation for the treatment of tumors, inflammation, hyperglycemia, lipid-lowering and weight-loss, oxidative stress and other diseases with nuciferine. CONCLUSION: Nuciferine has been clinically used to treat hyperlipidemia and aid in weight loss due to its effects on lipid levels, insulin secretion, vasodilation, blood pressure reduction, anti-tumor properties, and immune enhancement. However, other potential benefits of nuciferine have not yet been fully explored in clinical practice. Future research should delve deeper into its molecular structure, toxicity, side effects, and clinical pharmacology to uncover its full range of effects and pave the way for its safe and expanded clinical use.

Pallidal versus subthalamic deep brain stimulation for Meige syndrome: A systematic review and meta-analysis.

Background: Globus pallidus internus (GPi) and subthalamic nucleus (STN) are two common deep brain stimulation (DBS) targets. This meta-analysis was to compared the efficacy and safety of these two DBS targets for the treatment of Meige syndrome (MS). Methods: A systematic search was performed using EMBASE, MEDLINE, the Cochrane Library, and ClinicalTrials.gov to identify DBS trials for MS. Review Manager 5.3 was used to perform meta-analysis and the mean difference (MD) was analyzed and calculated with a random effect model. Pearson's correlation coefficients and meta-regression analyses were utilized to identify relevant predictive markers. Results: Twenty trials involving 188 participants with GPi-DBS and 110 individuals with STN-DBS were eligible. Both groups showed improvement of the Burke-Fahn-Marsden Dystonia Rating Scale-Movement (BFMDRS-M) and Disability (BFMDRS-D) scores (BFMDRS-M: MD = 10.57 [7.74-13.41] for GPi-DBS, and MD = 8.59 [4.08-13.11] for STN-DBS; BFMDRS-D: MD = 5.96 [3.15-8.77] for GPi-DBS, and MD = 4.71 [1.38-8.04] for STN-DBS; all P < 0.001) from baseline to the final follow-up, while no notable disparity in improvement rates was observed between them. Stimulation-related complications occurrence was also similar between two groups (38.54 ± 24.07% vs. 43.17 ± 29.12%, P = 0.7594). Simultaneously, preoperative BFMDRS-M score and disease duration were positively connected with the relative changes in BFMDRS-M score at the final visit. Conclusion: Both GPi-DBS and STN-DBS are effective MS therapies, with no differences in efficacy or the frequency of stimulation-related problems. Higher preoperative scores and longer disease duration probably predict greater improvement.

Mechanisms of Bushenyiqi decoction in the treatment of asthma: an investigation based on network pharmacology with experimental validation.

Background and purpose: The Bushenyiqi decoction (BYD), a contemporary prescription of traditional Chinese medicine (TCM), has been observed to significantly ameliorate asthma symptoms in patients based on clinical observations. Although multi-component and multi-target characteristics are important attributes of BYD treatment, its pharmacological effect on asthma and the underlying mechanism of action remain unclear. Method: Network pharmacology: the asthma-related genes were retrieved from the GeneCards and OMIM database. The active constituents of BYD and their corresponding target genes were collected from the TCMSP database. The underlying pathways associated with overlapping targets between BYD and asthma were identified through GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis. Experimental validation: pulmonary function tests, enzyme-linked immunosorbent assay (ELISA), Hematoxylin and eosin (HE), periodic acid-Schiff (PAS), and Masson's trichrome stainings were conducted to validate the efficacy of BYD in ameliorating airway inflammation in allergic asthma mice. Western blot (WB) and molecular docking were performed to confirm the involvement of the underlying pathway in BYD treatment of asthma. Results: The results of animal experiments demonstrated that BYD may improve airway responsiveness and suppress airway inflammation in allergic asthma mice. The network pharmacological analysis revealed the involvement of 11 potentially key active components, 9 potential key targets, and the phosphatidylinositol3 kinase-RAC-α serine/threonine-protein kinase (PI3K/AKT) signaling pathway in the mechanism of action of BYD for asthma treatment. Our findings have confirmed that BYD effectively alleviated airway inflammation by targeting interleukin 6 (IL-6), epidermal growth factor receptor (EGFR), and hypoxia inducible factor 1 alpha (HIF1A), with quercetin, kaempferol, and luteolin performing as the pivotal active constituents. BYD may potentially reduce inflammatory cell infiltration in lung tissues by regulating the PI3K/AKT signaling pathway. Conclusion: In conclusion, the integration of network pharmacology and biological experiments has demonstrated that key constituents of BYD, such as quercetin, kaempferol, and luteolin, exhibit targeted effects on IL-6, EGFR, and HIF1A in combating asthma-related inflammation through inhibition of the PI3K/AKT signaling pathway. The findings of this investigation provide evidence supporting the effectiveness of TCM's "bushenyiqi" therapy in asthma management, as corroborated by contemporary medical technology.

Retraction: An MSN-PEG-IP drug delivery system and IL13Rα2 as targeted therapy for glioma.

Retraction of 'An MSN-PEG-IP drug delivery system and IL13Rα2 as targeted therapy for glioma' by Jinlong Shi et al., Nanoscale, 2017, 9, 8970-8981, https://doi.org/10.1039/C6NR08786H.

Study on plasma metabolomics profiling of depression in Chinese community-dwelling older adults based on untargeted LC/GC‒MS.

Depression is a serious psychiatric illness that causes great inconvenience to the lives of elderly individuals. However, the diagnosis of depression is somewhat subjective. Nontargeted gas chromatography (GC)/liquid chromatography (LC)-mass spectrometry (MS) was used to study the plasma metabolic profile and identify objective markers for depression and metabolic pathway variation. We recruited 379 Chinese community-dwelling individuals aged ≥ 65. Plasma samples were collected and detected by GC/LC‒MS. Orthogonal partial least squares discriminant analysis and a heatmap were utilized to distinguish the metabolites. Receiver operating characteristic curves were constructed to evaluate the diagnostic value of these differential metabolites. Additionally, metabolic pathway enrichment was performed to reveal metabolic pathway variation. According to our standard, 49 people were included in the depression cohort (DC), and 49 people age- and sex-matched individuals were included in the non-depression cohort (NDC). 64 metabolites identified via GC‒MS and 73 metabolites identified via LC‒MS had significant contributions to the differentiation between the DC and NDC, with VIP values > 1 and p values < 0.05. Three substances were detected by both methods: hypoxanthine, phytosphingosine, and xanthine. Furthermore, 1-(sn-glycero-3-phospho)-1D-myo-inositol had the largest area under the curve (AUC) value (AUC = 0.842). The purine metabolic pathway is the most important change in metabolic pathways. These findings show that there were differences in plasma metabolites between the depression cohort and the non-depression cohort. These identified differential metabolites may be markers of depression and can be used to study the changes in depression metabolic pathways.

Obesity alters inflammatory response in the pathology of asthma (Review).

Obesity is one of the comorbidities in patients with asthma and obese patients with asthma present with a distinct phenotype with more severe disease outcomes and reduced responsiveness to standard therapies. Although the full mechanisms of obesity­related asthma are still not completely understood, abnormal immune responses have been demonstrated to have a critical role in asthma pathogenesis. The present review summarizes the data from clinical, epidemiological and animal studies to provide an updated understanding of the immune responses in obesity­related asthma, as well as the effect of various factors, such as oxidative stress, mitochondrial dysfunction, genetics and epigenetics, on asthmatic inflammation. Further studies on the in­depth mechanisms are still required to develop novel preventive and therapeutic strategies for patients with asthma combined with obesity.

TREM-1, TREM-2 and their association with disease severity in patients with COVID-19.

BACKGROUND: Delayed diagnosis and inadequate treatment caused by limited biomarkers are associated with the outcomes of COVID-19 patients. It is necessary to identify other promising biomarkers and candidate targets for defining dysregulated inflammatory states. METHODS: The triggering receptors expressed on myeloid cell (TREM)-1 and TREM-2 expression from hospitalized COVID-19 patients were characterized using ELISA and flow cytometry, respectively. Their correlation with disease severity and contrast with the main clinical indicators were evaluated. RESULTS: Increased expression of soluble TREM-1 and TREM-2 in the plasma of COVID-19 patients was found compared to the control group. Moreover, membrane-bound TREM-1 and TREM-2 expression was upregulated on the cell surface of circulating blood T cells from COVID-19 patients. Correlation analysis showed that sTREM-2 levels were negatively correlated with PaO2/FiO2, but positively correlated with C-reactive protein (CRP), procalcitonin (PCT) and interleukin (IL)-6 levels. Receiver operating characteristic curve analysis indicated that the predictive efficacy of sTREM-1 and sTREM-2 was equivalent to CRP and IL-6, and a little better than absolute leukocyte or neutrophil count and PCT in distinguishing disease severity. CONCLUSION: TREM-2 and TREM-1 are critical host immune factors that response to SARS-COV-2 infection and could serve as potential diagnostic biomarkers and therapeutic targets for COVID-19.

The expression of soluble TREM-1 and TREM-2 in plasma and membrane-bound TREM-1 and TREM-2 on the cell surface was upregulated in COVID-19 patients.sTREM-2 level was negatively correlated with PaO₂/FiO₂, but positively correlated with CRP, PCT and IL-6 level, respectively.sTREM-1 and sTREM-2 exhibited potential predictive abilities, and their expression was equivalent to CRP and IL-6, and better than the absolute leukocytes or neutrophil counts and PCT in distinguishing disease severity.

Gut microbiota composition is associated with disease severity and host immune responses in COVID-19.

Background: Human gut microbiota play a crucial role in the immune response of the host to respiratory viral infection. However, evidence regarding the association between the gut microbiome, host immune responses, and disease severity in coronavirus disease 2019 (COVID-19) remains insufficient. Methods: To better comprehend the interactions between the host and gut microbiota in COVID-19, we conducted 16S rRNA sequencing and characterized the gut microbiome compositions in stool samples from 40 COVID-19 patients and 33 non-pneumonia controls. We assessed several hematological parameters to determine the immune status. Results: We found that the gut microbial composition was significantly changed in COVID-19 patients, which was characterized by increased opportunistic pathogens and decreased commensal bacteria. The frequency of prevalent opportunistic pathogens Enterococcus and Lactobacillus increased, especially in severe patients; yet the abundance of butyrate-producing bacteria, Faecalibacterium, Roseburia, and Anaerostipes, decreased significantly, and Faecalibacterium prausnitzii might help discriminate severe patients from moderate patients and non-pneumonia people. Furthermore, we then obtained a correlation map between the clinical characteristics of COVID-19 and severity-related gut microbiota. We observed a notable correlation between the abundance of Enterococcus faecium and abnormal neutrophil or lymphocyte percentage in all COVID-19 patients. Faecalibacterium was positively correlated with lymphocyte counts, while negatively correlated with neutrophil percentage. Conclusion: These results suggested that the gut microbiome could have a potential function in regulating host immune responses and impacting the severity or consequences of diseases.

Discovery of potential biomarkers for osteoporosis using LC/GC-MS metabolomic methods.

Purpose: For early diagnosis of osteoporosis (OP), plasma metabolomics of OP was studied by untargeted LC/GC-MS in a Chinese elderly population to find possible diagnostic biomarkers. Methods: A total of 379 Chinese community-dwelling older adults aged ≥65 years were recruited for this study. The BMD of the calcaneus was measured using quantitative ultrasound (QUS), and a T value ≤-2.5 was defined as OP. Twenty-nine men and 47 women with OP were screened, and 29 men and 36 women were matched according to age and BMI as normal controls using propensity matching. Plasma from these participants was first analyzed by untargeted LC/GC-MS, followed by FC and P values to screen for differential metabolites and heatmaps and box plots to differentiate metabolites between groups. Finally, metabolic pathway enrichment analysis of differential metabolites was performed based on KEGG, and pathways with P ≤ 0.05 were selected as enrichment pathways. Results: We screened metabolites with FC>1.2 or FC<1/1.2 and P<0.05 and found 33 differential metabolites in elderly men and 30 differential metabolites in elderly women that could be potential biomarkers for OP. 2-Aminomuconic acid semialdehyde (AUC=0.72, 95% CI 0.582-0.857, P=0.004) is highly likely to be a biomarker for screening OP in older men. Tetradecanedioic acid (AUC=0.70, 95% CI 0.575-0.818, P=0.004) is highly likely to be a biomarker for screening OP in older women. Conclusion: These findings can be applied to clinical work through further validation studies. This study also shows that metabolomic analysis has great potential for application in the early diagnosis and recurrence monitoring of OP in elderly individuals.

Lessons from SARS­CoV­2 and its variants (Review).

COVID­19 has swept through mainland China by human­to­human transmission. The rapid spread of SARS­CoV­2 and its variants, including the currently prevalent Omicron strain, pose a serious threat worldwide. The present review summarizes epidemiological investigation and etiological analysis of genomic, epidemiological, and pathological characteristics of the original strain and its variants, as well as progress in diagnosis and treatment. Prevention and control measures used during the current Omicron pandemic are discussed to provide further knowledge of SARS­CoV­2.

IL-27 attenuates airway inflammation and epithelial-mesenchymal transition in allergic asthmatic mice possibly via the RhoA/ROCK signalling pathway

Background: Asthma is an airway disease characterized by airflow limitation and various additional clinical manifestations. Repeated inflammatory stimulation of the airways leads to epithelial-mesenchymal transition (EMT) which aggravates subepithelial fibrosis during the process of airway remodelling and enhances resistance to corticosteroids and bronchodilators in refractory asthma. There is growing evidence that IL-27 modulates airway remodelling, however, the molecular mechanisms involving IL-27 and EMT are poorly understood. The objective of this study was to investigate the effects of IL-27 on ovalbumin (OVA)-challenged asthmatic mice in vivo and TGF-ß1-induced EMT in 16HBE cells in vitro. Methods: Airway inflammation, mucus secretion, and collagen deposition were analysed by conventional pathological techniques. The ratio of Th17 and Th9 cells in the spleen of mice was measured using flow cytometry, ELISA was performed for cytokine analysis to identify EMT-related molecules and signalling pathways, and other molecular and cellular techniques were used to explore the functional mechanism involving IL-27 and EMT. Results: Airway inflammation in asthmatic mice was significantly alleviated by IL-27, with downregulation of RhoA and ROCK, upregulation of E-cadherin, and a decrease of vimentin and α-SMA expression, compared to asthmatic mice. Moreover, the frequency of Th17 and Th9 cells in the spleen of asthmatic mice decreased following treatment with IL-27. In TGF-ß1-induced 16HBE cells, the addition of IL-27 was shown to inhibit EMT, based on the expression of E-cadherin, vimentin, and α-SMA. Conclusion: Intranasal administration of IL-27 attenuates airway inflammation and EMT in a murine model of allergic asthma possibly by downregulating the RhoA/ROCK signalling pathway.

Interleukin­27 ameliorates allergic asthma by alleviating the lung Th2 inflammatory environment.

Interleukin (IL)­27 can inhibit the differentiation of Th2 cells and plays a role in the development of asthma. However, whether the therapeutic administration of IL­27 in a mouse model of asthma can inhibit allergic responses remains a matter of debate. Additionally, the mechanisms through which IL­27 ameliorates inflammatory responses in asthma are not yet fully understood. Thus, the aim of the present study was to examine the effects of IL­27 on asthma using a mouse model and to elucidate the underlying mechanisms. For this purpose, mice received an intranasal administration of IL­27 and the total and differential cell counts, levels of cytokines and type 1 regulatory T (Tr1) cells in the lungs were detected. The protein and mRNA levels of signal transducer and activator of transcription (STAT)1 and STAT3 were analyzed and airway remodeling was assessed. The results indicated that IL­27 did not ameliorate airway inflammation, airway hyperresponsiveness, and airway remolding when administrated therapeutically. Preventatively, the administration of IL­27 decreased the concentrations of Th2 cytokines and increased the number of Tr1 cells. The protein and mRNA levels of STAT1 and STAT3 were increased. Taken together, these findings demonstrate that the prophylactic administration of IL­27 ameliorates asthma by alleviating the lung Th2 inflammatory environment through the restoration of both the STAT1 and STAT3 pathways. IL­27 may thus prove to be useful as a novel agent for the prevention of asthma.