Self-Efficacy's Mediating Role in the Relationship Between Self-Perceived Burden and Health-Related Quality of Life Among Older-Adult Inpatients in China: A Cross-Sectional Study.

Purpose: This study investigated the current state of self-efficacy and the association between self-perceived burden (SPB) and health-related quality of life (HRQoL) among Chinese older-adult inpatients. Methods: A cross-sectional study was conducted using convenience sampling to survey Chinese older-adult inpatients. Data regarding demographic characteristics, self-efficacy, SPB, and HRQoL were collected. Pearson's correlation analysis was used to examine the correlations among the research variables. SPSS® Statistics V26.0, and SPSS® PROCESS Macro Model 4 were used to analyze the available data. The bootstrap method was used to analyze the mediating role of self-efficacy. Results: Survey participants included 514 older-adult inpatients, with a mean age of 72.28±5.58 years. Self-efficacy (r=0.471, p<0.01) was positively correlated with HRQoL, whereas self-efficacy (r=-0.891, p<0.01) and HRQoL (r=-0.516, p<0.01) were negatively correlated with SPB. The mediating effect analysis revealed that self-efficacy either completely or partially mediated the effect of SPB on HRQoL, with the indirect effect accounting for 30.2% of the total. Conclusion: This study provides a mediating model suggesting that SPB exerts both direct and indirect effects on the HRQoL of older-adult inpatients through self-efficacy.

The relationship between red cell distribution width, serum calcium ratio, and in-hospital mortality among patients with acute respiratory failure: A retrospective cohort study of the MIMIC-IV database.

To investigate the impact of RDW/CA (the ratio of red cell distribution width to calcium) on in-hospital mortality in patients with acute respiratory failure (ARF). This retrospective cohort study analyzed the data of 6981 ARF patients from the Medical Information Mart for Intensive Care (MIMIC-IV) database 2.0. Critically ill participants between 2008 and 2019 at the Beth Israel Deaconess Medical Center in Boston. The primary outcome of interest was in-hospital mortality. A Cox proportional hazards regression model was used to determine whether the RDW/CA ratio independently correlated with in-hospital mortality. The Kaplan-Meier method was used to plot the survival curves of the RDW/CA. Subgroup analyses were performed to measure the mortality across various subgroups. After adjusting for potential covariates, we found that a higher RDW/CA was associated with an increased risk of in-hospital mortality (HR = 1.17, 95% CI: 1.01-1.35, P = .0365) in ARF patients. A nonlinear relationship was observed between RDW/CA and in-hospital mortality, with an inflection point of 1.97. When RDW/CA ≥ 1.97 was positively correlated with in-hospital mortality in patients with ARF (HR = 1.554, 95% CI: 1.183-2.042, P = .0015). The Kaplan-Meier curve indicated the higher survival rates for RDW/CA < 1.97 and the lower for RDW/CA ≥ 1.97 after adjustment for age, gender, body mass index, and ethnicity. RDW/CA is an independent predictor of in-hospital mortality in patients with ARF. Furthermore, a nonlinear relationship was observed between RDW/CA and in-hospital mortality in patients with ARF.

PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, relieves airway hyperresponsiveness, mucus hypersecretion and inflammation in a murine asthma model.

BACKGROUND: Tyrosine kinase and phosphoinositide kinase pathways play important roles in asthma formation. As a dual tyrosine and phosphoinositide kinase inhibitor, PP121 has shown anticancer efficacy in multiple tumors. However, the study of PP121 in pulmonary diseases is still limited. Herein, we investigated the therapeutic activities of PP121 in asthma treatment. METHODS: Tension measurements and patch clamp recordings were made to investigate the anticontractile characteristics of PP121 in vitro. Then, an asthma mouse model was established to further explore the therapeutic characteristics of PP121 via measurement of respiratory system resistance, histological analysis and western blotting. RESULTS: We discovered that PP121 could relax precontracted mouse tracheal rings (mTRs) by blocking certain ion channels, including L-type voltage-dependent Ca2+ channels (L-VDCCs), nonselective cation channels (NSCCs), transient receptor potential channels (TRPCs), Na+/Ca2+ exchangers (NCXs) and K+ channels, and accelerating calcium mobilization. Furthermore, PP121 relieved asthmatic pathological features, including airway hyperresponsiveness, systematic inflammation and mucus secretion, via downregulation of inflammatory factors, mucins and the mitogen-activated protein kinase (MAPK)/Akt signaling pathway in asthmatic mice. CONCLUSION: In summary, PP121 exerts dual anti-contractile and anti-inflammatory effects in asthma treatment, which suggests that PP121 might be a promising therapeutic compound and shed new light on asthma therapy.

The influence of flow distribution strategy for the quantification of pressure- and wall shear stress-derived parameters in the coronary artery: A CTA-based computational fluid dynamics analysis.

For image-based computational fluid dynamics (CFD) analysis to characterize the local coronary hemodynamic environment, the accuracy depends on the flow rate which is in turn associated with outlet branches' morphology. A good flow distribution strategy is important to mitigate the effect when certain branches cannot be considered. In this study, stenotic coronary arteries from 13 patients were used to analyze the effect of missing branches and different flow distribution strategies. Pressure- and wall shear stress (WSS)-derived parameters around the stenotic region (ROI) were compared, including fractional flow reserve (CT-FFR), instantaneous wave-free ratio (CT-iFR), resting distal to aortic coronary pressure (CT-Pd/Pa), time-averaged WSS, oscillatory shear index (OSI) and relative residence time (RRT). Three flow distribution strategies were the Huo-Kassab model at distal outlets (Type I), flow distribution based on outlet resistances (Type II), and a developed algorithm distributing flow at each bifurcation until the final outlets (Type III). Results showed that Type III strategy for models with truncated branch(es) had a good agreement in both pressure- and WSS-related results (interquatile range less than 0.12% and 4.02%, respectively) with the baseline model around the ROI. The relative difference of pressure- and WSS-related results were correlated with the flow differences in the ROI to the baseline mode. Type III strategy had the best performance in maintaining the flow in intermediate branches. It is recommended for CFD analysis. Removal of branches distal to a stenosis can be undertaken with an improved performance and maintained accuracy, while those proximal to the ROI should be kept.

Duloxetine HCl Alleviates Asthma Symptoms by Regulating PI3K/AKT/mTOR and Nrf2/HO-1 Signaling Pathways.

Asthma is an inflammatory disease characterized by airway hyperresponsiveness, airway remodeling, and airway inflammation. In recent years, the prevalence of asthma has been increasing steadily and the pathogenesis of asthma varies from person to person. Due to poor compliance or resistance, existing drugs cannot achieve the desired therapeutic effect. Therefore, developing or screening asthma therapeutic drugs with high curative effects, low toxicity, and strong specificity is very urgent. Duloxetine HCl (DUX) is a selective serotonin and norepinephrine reuptake inhibitor, and it was mainly used to treat depression, osteoarthritis, and neuropathic pain. It was also reported that DUX has potential anti-infection, anti-inflammation, analgesic, antioxidative, and other pharmacological effects. However, whether DUX has some effects on asthma remains unknown. In order to investigate it, a series of ex vivo and in vivo experiments, including biological tension tests, patch clamp, histopathological analysis, lung function detection, oxidative stress enzyme activity detection, and molecular biology experiments, were designed in this study. We found that DUX can not only relax high potassium or ACh precontracted tracheal smooth muscle by regulating L-type voltage-dependent Ca2+ channel (L-VDCC) and nonselective cation channel (NSCC) ion channels but also alleviate asthma symptoms through anti-inflammatory and antioxidative response regulated by PI3K/AKT/mTOR and Nrf2/HO-1 signaling pathways. Our data suggests that DUX is expected to become a potential new drug for relieving or treating asthma.

The Relationship Between Mindfulness, Fatigue, and Perceived Symptoms Among Frontline Nurses Who Performed Nucleic Acid Sample Collection During the COVID-19 in China: A Cross-Sectional Study.

Objective: Given the immense stress faced by medical staff during the COVID-19 pandemic, this study aimed to evaluate the relationship between mindful attention awareness, fatigue, and perceived symptoms among frontline nurses who performed nucleic acid sample collection during the COVID-19 pandemic, to reduce their fatigue and help them cope with perceived uncomfortable symptoms. Methods: A convenience sampling method was used to survey nurses who travelled to Hainan for nucleic acid sampling in August 2022 using an online (WeChat) questionnaire. A total of 514 frontline nurses who performed nucleic acid tests completed the questionnaire. The questionnaire covered basic demographic information, Mindful Attention Awareness Scale (MAAS) ratings, and Fatigue Severity Scale (FSS) ratings. Spearman correlation analysis was used to separate the relationship between MASS and FSS, and univariate and multivariate factor analyses were used to explore the relevant influences contributing to the occurrence of fatigue. Results: A total of 514 individuals completed the survey,93.97% (n=483) were female, mean age was 31.15 ± 5.7, MASS score was 69.01 ± 13.53, and 296 (57.59%) nurses experienced symptoms of fatigue during the auxiliary period. Spearman correlation analysis showed that FSS was associated with MASS. Multifactorial analysis showed that sex, age, marital status, fertility status, years of work, adaptation to dietary habits, hidrorrhea, and MAAS scores affected the presence of fatigue symptoms among the medical staff in Hainan (P<0.05). Conclusion: The psychological status of frontline nurses undergoing nucleic acid testing during the pandemic was poor, and the appearance of fatigue symptoms could be effectively reduced by increasing levels of positive thinking among medical staff to help them cope with public health emergencies.

Applications of nanobodies in the prevention, detection, and treatment of the evolving SARS-CoV-2.

Global health and economy are deeply influenced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its newly emerging variants. Nanobodies with nanometer-scale size are promising for the detection and treatment of SARS-CoV-2 and its variants because they are superior to conventional antibodies in terms of cryptic epitope accessibility, tissue penetration, cost, formatting adaptability, and especially protein stability, which enables their aerosolized specific delivery to lung tissues. This review summarizes the progress in the prevention, detection, and treatment of SARS-CoV-2 using nanobodies, as well as strategies to combat the evolving SARS-CoV-2 variants. Generally, highly efficient generation of potent broad-spectrum nanobodies targeting conserved epitopes or further construction of multivalent formats targeting non-overlapping epitopes can promote neutralizing activity against SARS-CoV-2 variants and suppress immune escape.

Andrographolide Promotes Uptake of Glucose and GLUT4 Transport through the PKC Pathway in L6 Cells.

Glucose transporter 4 (GLUT4) is a membrane protein that regulates blood glucose balance and is closely related to type 2 diabetes. Andrographolide (AND) is a diterpene lactone extracted from herbal medicine Andrographis paniculata, which has a variety of biological activities. In this study, the antidiabetic effect of AND in L6 cells and its mechanism were investigated. The uptake of glucose of L6 cells was detected by a glucose assay kit. The expression of GLUT4 and phosphorylation of protein kinase B (PKB/Akt), AMP-dependent protein kinase (AMPK), and protein kinase C (PKC) were detected by Western blot. At the same time, the intracellular Ca2+ levels and GLUT4 translocation in myc-GLUT4-mOrange-L6 cells were detected by confocal laser scanning microscopy. The results showed that AND enhanced the uptake of glucose, GLUT4 expression and fusion with plasma membrane in L6 cells. Meanwhile, AND also significantly activated the phosphorylation of AMPK and PKC and increased the concentration of intracellular Ca2+. AND-induced GLUT4 expression was significantly inhibited by a PKC inhibitor (Gö6983). In addition, in the case of 0 mM extracellular Ca2+ and 0 mM extracellular Ca2+ + 10 µM BAPTA-AM (intracellular Ca2+ chelator), AND induced the translocation of GLUT4, and the uptake of glucose was significantly inhibited. Therefore, we concluded that AND promoted the expression of GLUT4 and its fusion with plasma membrane in L6 cells through PKC pathways in a Ca2+-dependent manner, thereby increasing the uptake of glucose.

Male nurses' work performance: A cross sectional study.

BACKGROUND: Nursing performance is closely related to the success of hospital and patient outcome. Recently, the proportion of male nurses has gradually increased. However, we do not know how these male nurses perform in clinical work. The purpose of this study was to understand the job performance of male nurses in China and to identify their risk factors. METHODS: This is a cross-sectional study. We contacted all the 30 public tertiary hospitals in Hunan Province and 26 of them cooperated. All the 647 male nurses in these hospitals were given questionnaires face-to-face between April 7 and August 8, 2020. The questionnaire included demographic information and the Schwirian's Six Dimension Scale. We also collected the family attitude and the main reason for choosing nursing. We then performed descriptive analyses and liner regressions on the collected data. RESULTS: We obtained valid questionnaires from 599 individuals. The median age of these male nurses was 26 years old and the nursing age was 4 years. They were mainly distributed in intensive care unit (ICU) (36.12%), operating room (27.42%), and emergency department (23.08%). And the means of the total scores for work performance was 176.42 (standard deviation (SD) = 20.62). The result of the regression shows that length of service, relationship status, educational level, department, main reason for choosing nursing, and family attitude are all risk factors of male nurses' work performance. CONCLUSION: Chinese male nurses are younger and have shorter working years. They mainly work in departments with higher work intensity and greater pressure. In addition, we found that years of service, education, marital status, department and main reasons for choosing nursing as factors influencing the job performance of male nurses.

MiR-574-3p inhibits glucose toxicity-induced pancreatic ß-cell dysfunction by suppressing PRMT1.

BACKGROUND: Pancreatic ß-cell dysfunction is commonly observed in patients with type 2 diabetes mellitus. Protein arginine methyltransferase 1 (PRMT1) plays an important role in pancreatic ß-cell dysfunction. However, the detailed mechanisms remain largely unknown. METHODS: RT-qPCR, western blotting, and immunofluorescence assays were used to evaluate PRMT1 and miR-574-3p levels. Cell Counting Kit-8, Advanced Dlycation End products (AGEs), Reactive Oxygen Species (ROS), and glucose-stimulated insulin secretion were assayed, and flow cytometry and RT-qPCR were performed to detect the role of PRMT1 and miR-574-3p in MIN6 cells. Luciferase reporter assays were performed to determine the interactions between PRMT1 and miR-574-3p. RESULTS: High-glucose treatment resulted in the high expression of PRMT1. PRMT1 silencing could alleviate the reduced proliferation, insulin secretion, and GLUT1 level, in addition to suppressing the induced apoptosis, and AGEs and ROS levels, under high glucose conditions. MiR-574-3p was established as an upstream regulator of PRMT1 using luciferase reporter assays. More importantly, miR-574-3p reversed the effect of PRMT1 silencing in MIN6 cells. CONCLUSIONS: miR-574-3p suppresses glucose toxicity-induced pancreatic ß-cell dysfunction by targeting PRMT1.

Risk factors associated with preterm birth after IVF/ICSI.

In vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) is associated with an increased risk of preterm (33rd-37th gestational week) and early preterm birth (20th-32nd gestational week). The underlying general and procedure related risk factors are not well understood so far. 4328 infertile women undergoing IVF/ICSI were entered into this study. The study population was divided into three groups: (a) early preterm birth group (n = 66), (b) preterm birth group (n = 675) and (c) full-term birth group (n = 3653). Odds for preterm birth were calculated by stepwise multivariate logistic regression analysis. We identified seven independent risk factors for preterm birth and four independent risk factors for early preterm birth. Older (> 39) or younger (< 25) maternal age (OR: 1.504, 95% CI 1.108-2.042, P = 0.009; OR: 2.125, 95% CI 1.049-4.304, P = 0.036, respectively), multiple pregnancy (OR: 9.780, 95% CI 8.014-11.935, P < 0.001; OR: 8.588, 95% CI 4.866-15.157, P < 0.001, respectively), placenta previa (OR: 14.954, 95% CI 8.053-27.767, P < 0.001; OR: 16.479, 95% CI 4.381-61.976, P < 0.001, respectively), and embryo reduction (OR: 3.547, 95% CI 1.736-7.249, P = 0.001; OR: 7.145, 95% CI 1.990-25.663, P = 0.003, respectively) were associated with preterm birth and early preterm birth, whereas gestational hypertension (OR: 2.494, 95% CI 1.770-3.514, P < 0.001), elevated triglycerides (OR: 1.120, 95% CI 1.011-1.240, P = 0.030) and shorter activated partial thromboplastin time (OR: 0.967, 95% CI 0.949-0.985, P < 0.001) were associated only with preterm birth. In conclusion, preterm and early preterm birth risk factors in patients undergoing assisted IVF/ICSI are in general similar to those in natural pregnancy. The lack of some associations in the early preterm group was most likely due to the lower number of early preterm birth cases. Only embryo reduction represents an IVF/ICSI specific risk factor.

Glucose Uptake Is Increased by Estradiol Dipropionate in L6 Skeletal Muscle Cells.

GLUT4 is an important glucose transporter, which is closely related to insulin resistance and type 2 diabetes. In this study, we investigated the mechanism of Estradiol Dipropionate (EDP) on uptake of glucose in L6 skeletal muscle cells. In our study, we confirmed that EDP promoted uptake of glucose in L6 skeletal muscle cells in both normal and insulin resistant models. Western blot indicated that EDP accelerated GLUT4 expression and significantly activated AMPK and PKC phosphorylation; the expression of GLUT4 was significantly inhibited by AMPK inhibitor compound C and PKC inhibitor Gö6983, but not by Wortmannin (Akt inhibitor). Meanwhile, EDP boosted GLUT4 expression, and also increased intracellular Ca2+ levels. In the presence of 2 mM, 0 mM extracellular Ca2+ and 0 mM extracellular Ca2+ + BAPTA-AM, the involvement of intracellular Ca2+ levels contribute to EDP-induced GLUT4 expression and fusion with plasma membrane. Therefore, this study investigated whether EDP promoted GLUT4 expression through AMPK and PKC signaling pathways, thereby enhancing GLUT4 uptake of glucose and fusion into plasma membrane in L6 skeletal muscle cells. In addition, both EDP induced GLUT4 translocation and uptake of glucose were Ca2+ dependent. These findings suggested that EDP may be potential drug for the treatment of type 2 diabetes.

Maternal tobacco exposure during pregnancy and allergic rhinitis in offspring: A systematic review and meta-analysis.

BACKGROUND: Maternal tobacco exposure during pregnancy is known to cause a potential hazard to the offspring's health. So far, published studies have shown no consistent results with whether tobacco exposure in utero is causally linked to the development of allergic rhinitis in offspring. The aim of this study was to comprehensively evaluate the association between maternal tobacco exposure during pregnancy and allergic rhinitis in offspring by meta-analysis and to provide reference for clinical work. METHODS: Literatures were searched in CNKI, Wanfang Data, VIP, SinoMed, PubMed, Web of science and Embase up to September 30,2020. Screening, inclusion, quality assessment, data extraction and data analysis of the literatures were conducted. Meta-analysis was performed with Revman 5.3 and State15.1 software. Odds ratio (OR) and 95%CI were used as observation indicators. RESULTS: We had retrieved 16 articles with 22 independent datasets and 11,49,879 sample size. When all the studies were analyzed together, the results showed that maternal smoking exposure during pregnancy would increase the risk of allergic rhinitis in offspring (OR = 1.13, 95%CI:1.02-1.26), especially maternal passive smoking during pregnancy (OR = 1.39, 95%CI:1.05-1.84). But subgroup analysis showed that maternal active smoking during pregnancy was only significantly associated with offspring allergic rhinitis in cross-sectional studies (OR = 1.24, 95%CI:1.07-1.45) and study done in America study (OR = 1.22, 95%CI:1.05-1.42). CONCLUSIONS: Tobacco exposure during pregnancy could increase the risk of allergic rhinitis in offspring. The importance of avoiding prenatal tobacco exposure should be emphasized more for the health of next generation in the public.

[Generation and phenotypic characterization of S100A9 gene knockout mice by CRISPR/Cas9-mediated gene targeting].

S100 calcium binding protein A9 (S100A9) is involved in a variety of biological processes such as inflammation and tumor cell migration and invasion regulation. The purpose of this study was to construct S100A9 gene-edited mice by using CRISPR/Cas9 technology, thereby providing an animal model for exploring the biological functions of this gene. According to the S100A9 gene sequence, the single-stranded small guide RNA (sgRNA) targeting exons 2 and 3 was transcribed in vitro, and a mixture of Cas9 mRNA and candidate sgRNA was injected into mouse fertilized eggs by microinjection. Early embryos were obtained and transferred to surrogate mice, and F0 mice were obtained and identified by PCR identification and gene sequencing. F0 mice were further mated with wild-type C57BL/6 mice to obtain F1 heterozygous mice, and then homozygous offspring were obtained through F1 mice self-crossing. Real-time PCR, Western blot and immunohistochemistry (IHC) were used to verify the expression and distribution of S100A9. In order to observe the pathological changes of mouse lung tissue using HE staining, an allergic asthma model was induced by ovalbumin from chicken egg white (OVA). The results showed that the 2 492 bp of exons 2, 3 of the S100A9 gene was successfully knocked out, and S100A9-/- mice with stable inheritance were obtained. Furthermore, it was found that S100A9 gene was highly expressed in the lung and spleen of wild-type mice. The expression of S100A9 mRNA and protein was not detected in the lung and spleen of S100A9-/- mice. However, compared with wild-type mice, the lungs of S100A9-/- mice showed a significantly worse inflammatory phenotype, and the proportion of eosinophils in bronchoalveolar lavage fluid (BALF) was significantly increased in response to the treatment of OVA. These results suggest we have successfully constructed a new strain of S100A9-/- mice, and preliminarily confirmed that the lack of S100A9 function can aggravate airway inflammation in asthmatic mice, providing a new mouse model for further study of S100A9 gene function.

Proteomic Analysis Reveals That Placenta-Specific Protein 9 Inhibits Proliferation and Stimulates Motility of Human Bronchial Epithelial Cells.

Placenta-specific protein 9 (PLAC9) is a putative secretory protein that was initially identified in the placenta and is involved in cell proliferation and motility. Bioinformatics analyses revealed that PLAC9 is repressed in lung cancers (LCs), especially lung adenocarcinomas, compared to that in the paired adjacent normal tissues, indicating that PLAC9 might be involved in the pathogenesis of pulmonary diseases. To investigate the potential role of PLAC9 in the abnormal reprogramming of airway epithelial cells (AECs), a key cause of pulmonary diseases, we constructed a stable PLAC9-overexpressing human bronchial epithelial cell line (16HBE-GFP-Plac9). We utilized the proteomic approach isobaric tag for relative and absolute quantification (iTRAQ) to analyze the effect of PLAC9 on cellular protein composition. Gene ontology (GO) and pathway analyses revealed that GO terms and pathways associated with cell proliferation, cell cycle progression, and cell motility and migration were significantly enriched among the proteins regulated by PLAC9. Our in vitro results showed that PLAC9 overexpression reduced cell proliferation, altered cell cycle progression, and increased cell motility, including migration and invasion. Our findings suggest that PLAC9 inhibits cell proliferation through S phase arrest by altering the expression levels of cyclin/cyclin-dependent kinases (CDKs) and promotes cell motility, likely via the concerted actions of cyclins, E-cadherin, and vimentin. Since these mechanisms may underlie PLAC9-mediated abnormal human bronchial pathogenesis, our study provides a basis for the development of molecular targeted treatments for LCs.

Dandelion extract relaxes mouse airway smooth muscle by blocking VDLCC and NSCC channels.

BACKGROUND: Asthma is one of the main intractable diseases recognized by the international medical community. The current widely used bronchodilators for asthma-ß2-adrenal receptor agonists-have limited therapeutic effects, necessitating the development of novel antiasthma drugs with increased efficacy and fewer adverse effects. In this study, we investigated the relaxant effects and underlying mechanism of an ethyl acetate extract from dandelion (EAED) on mouse airway smooth muscle. METHODS: The effects of EAED on agonist-induced precontraction in mouse airway smooth muscle were evaluated with force measurement. Mouse lung slices were used to study the effects of EAED on bronchial smooth muscle. The intracellular Ca2+ concentration was measured using a calcium imaging system. L-type voltage-dependent calcium channel (VDLCC) and non-selective cationic channel (NSCC) currents were measured by patch-clamp. The lung functions of healthy and asthmatic mouse groups were assessed via the forced oscillation technique. RESULTS: EAED inhibits acetylcholine-induced sustained contractions of whole airway smooth muscle by inhibiting VDLCCs, NSCCs, and some unknown channels, reduces the agonist-induced increase in the cytosolic free Ca2+ concentration in airway smooth muscle cells, blocks VDLCC and NSCC currents, and relieves the respiratory resistance of healthy and asthmatic mice. CONCLUSIONS: EAED may have potential beneficial effects on mitigating asthma attacks.

Anti-Contractile and Anti-Inflammatory Effects of Diacerein on Isolated Mouse Airways Smooth Muscle and Mouse Asthma Model.

Characterized by abnormal smooth muscle contractility and airway inflammation, asthma is one of the most common airway diseases worldwide. Diacerein is a well-known anti-inflammatory drug, widely used in osteoarthritis. In current study, the innovative usage of diacerein in anti-contractile and anti-inflammatory treatment of asthma was studied. In vitro experiments including tension measurement and patch-clamp technique and in vivo experiments including establishment of mice model and measurement of respiratory resistance were applied to explore the role of diacerein in asthma. It turned out that agonist-precontracted mouse airway smooth muscle could be relaxed by diacerein via intracellular and extracellular calcium mobilization which was mediated by switched voltage-dependent L-type Ca2+ channels, non-selective cation channels, large-conductance Ca2+-activated K+ channel, and Na+/Ca2+ exchangers. Furthermore, diacerein could relieve bronchospasm and control airway inflammation in asthmatic mice via reduction of several inflammatory factors. Our studies elucidated the potential therapeutic property of diacerein in asthma treatment and the possible underlying mechanism. It also confirmed that new uses for already-approved drugs could be an important form of innovation.

Suvorexant for the prevention of delirium: A meta-analysis.

BACKGROUND: Delirium is a frequently encountered complication, which is associated with increased mortality. Suvorexant, an approved agent for the treatment of insomnia, is recently suggested to be also effective for prevention of delirium by some authors. However, a consensus has yet to be reached. The goal of this study was to perform a meta-analysis to overall estimate the effectiveness of suvorexant in preventing delirium and its related consequences. METHODS: Eligible studies were identified by searching online databases of PubMed, EMBASE, and Cochrane Library. The pooled OR was calculated for binary outcomes (e.g., the incidence of delirium, mortality, or adverse events), while standardized mean difference (SMD) were expressed for continuous outcomes (e.g., time to delirium onset, length of stay in hospital and ICU, time on ventilation). RESULTS: Seven studies which comprised 402 suvorexant treatment patients and 487 patients with control treatment were included in this meta-analysis. Overall, pooled analysis indicated the incidence of delirium could be significantly reduced (OR, 0.30; P < .001) and time to delirium onset was significantly lengthened (SMD, 0.44; P = .006) in patients undergoing suvorexant treatment compared with controls. Suvorexant had no beneficial effects on the secondary outcomes [length of stay in hospital (SMD, -0.65; P = .161) and ICU (SMD, 0.34; P = .297), time on ventilation (SMD, 1.09; P = .318), drug-related adverse events (OR, drug-related adverse events (OR, 1.66; P = .319) and mortality (OR, 2.21; P = .261)]. Subgroup analysis also confirmed the benefit of suvorexant on the development of delirium, which was significant in any subgroup. CONCLUSION: Suvorexant should be recommended for the prevention of delirium in clinic.

Folium Sennae and emodin reverse airway smooth muscle contraction.

The objective of this project was to find a bronchodilatory compound from herbs and clarify the mechanism. We found that the ethanol extract of Folium Sennae (EEFS) can relax airway smooth muscle (ASM). EEFS inhibited ASM contraction, induced by acetylcholine, in mouse tracheal rings and lung slices. High-performance liquid chromatography assay showed that EEFS contained emodin. Emodin had a similar reversal action. Acetylcholine-evoked contraction was also partially reduced by nifedipine (a selective inhibitor of L-type voltage-dependent Ca2+ channels, LVDCCs), YM-58483 (a selective inhibitor of store-operated Ca2+ entry, SOCE), as well as Y-27632 (an inhibitor of Rho-associated protein kinase). In addition, LVDCC- and SOCE-mediated currents and cytosolic Ca2+ elevations were inhibited by emodin. Emodin reversed acetylcholine-caused increases in phosphorylation of myosin phosphatase target subunit 1. Furthermore, emodin, in vivo, inhibited acetylcholine-induced respiratory system resistance in mice. These results indicate that EEFS-induced relaxation results from emodin inhibiting LVDCC, SOCE, and Ca2+ sensitization. These findings suggest that Folium Sennae and emodin may be new sources of bronchodilators.

Coptisine, a protoberberine alkaloid, relaxes mouse airway smooth muscle via blockade of VDLCCs and NSCCs.

BACKGROUND/AIMS: Recently, effective and purified ingredients of traditional Chinese medicine (TCM) were extracted to play crucial roles in the treatment of pulmonary diseases. Our previous research focused on TCM drug screening aimed at abnormal airway muscle contraction during respiratory diseases. Coptisine, an effective ingredient extracted from bitter herbs has shown a series of antioxidant, antibacterial, cardioprotective and neuroprotective pharmacological properties. In the current study, we questioned whether coptisine could also participate in asthma treatment through relaxing abnormal contracted mouse airway smooth muscle (ASM). The present study aimed to characterize the relaxant effects of coptisine on mouse ASM and uncover the underlying molecular mechanisms. METHODS: To investigate the role of coptisine on pre-contracted mouse ASM, a series of biological techniques, including force measurement and patch-clamp experiments were employed. RESULTS: Coptisine was found to inhibit high K+ or acetylcholine chloride (ACh)-induced pre-contracted mouse tracheal rings in a dose-dependent manner. Further research demonstrated that the coptisine-induced mouse ASM relaxation was mediated by alteration of calcium mobilization via voltage-dependent L-type Ca2+ channels (VDLCCs) and non-selective cation channels (NSCCs). CONCLUSION: Our data showed that mouse ASM could be relaxed by coptisine via altering the intracellular Ca2+ concentration through blocking VDLCCs and NSCCs, which suggested that this pharmacological active constituent might be classified as a potential new drug for the treatment of abnormal airway muscle contraction.