Exosomes derived from lung cancer cells confer cisplatin (DDP) resistance to other cancer cells. However, the underlying mechanism is still unknown. A549 resistance to DDP (A549/DDP) was established. Microarray was used to analyze microRNA (miRNA) expression profiles of A549 cells, A549/DDP cells, A549 exosomes, and A549/DDP exosomes. There was a strong correlation of miRNA profiles between exosomes and their maternal cells. A total of 11 miRNAs were significantly upregulated both in A549/DDP cells compared with A549 cells and in exosomes derived from A549/DDP cells in contrast to exosomes from A549 cells. A total of 31 downregulated miRNAs were also observed. miR-100–5p was the most prominent decreased miRNA in DDP-resistant exosomes compared with the corresponding sensitive ones. Downregulated miR-100–5p was proved to be involved in DDP resistance in A549 cells, and mammalian target of rapamycin (mTOR) expression was reverse regulated by miR-100–5p. Exosomes confer recipient cells’ resistance to DDP in an exosomal miR-100–5p-dependent manner with mTOR as its potential target both in vitro and in vivo. Exosomes from DDP-resistant lung cancer cells A549 can alter other lung cancer cells’ sensitivity to DDP in exosomal miR-100–5p-dependent manner. Our study provides new insights into the molecular mechanism of DDP resistance in lung cancer.
Background: Severe acute respiratory syndrome (SARS)-CoV-2-induced coronavirus disease-2019 (COVID-19) is a pandemic disease that affects > 2.8 million people worldwide, with numbers increasing dramatically daily. However, there is no specific treatment for COVID-19 and much remains unknown about this disease. Angiotensin-converting enzyme (ACE)2 is a cellular receptor of SARS-CoV-2. It is cleaved by type II transmembrane serine protease (TMPR SS)2 and disintegrin and metallopeptidase domain (ADAM)17 to assist viral entry into host cells. Clinically, SARS-CoV-2 infection may result in acute lung injury and lung fibrosis, but the underlying mechanisms of COVID-19 induced lung fibrosis are not fully understood. Methods: The networks of ACE2 and its interacting molecules were identified using bioinformatic methods. Their gene and protein expressions were measured in human epithelial cells after 24 h SARS-CoV-2 infection, or in existing datasets of lung fibrosis patients. Results: We confirmed the binding of SARS-CoV-2 and ACE2 by bioinformatic analysis. TMPRSS2, ADAM17, tissue inhibitor of metalloproteinase (TIMP)3, angiotensinogen (AGT), transformation growth factor beta (TGFB1), connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF) A and fibronectin (FN) were interacted with ACE2, and the mRNA and protein of these molecules were expressed in lung epithelial cells. SARS-CoV-2 infection increased ACE2, TGFB1, CTGF and FN1 mRNA that were drivers of lung fibrosis. These changes were also found in lung tissues from lung fibrosis patients. Conclusions: Therefore, SARS-CoV-2 binds with ACE2 and activates fibrosis-related genes and processes to induce lung fibrosis.
Background: No studies have been conducted to explore the associations between dietary patterns and obesity among older Chinese people, by considering gender and urbanization level differences. Methods: We analyzed data from the 2009 China Health and Nutrition Survey (2745 individuals, aged ≥ 60 years). Dietary data were obtained using 24 h-recall over three consecutive days. Height, Body Weight, and Waist Circumference were measured. Exploratory factor analysis was used to identify dietary patterns. Multinomial and Poisson regression models were used to examine the association between dietary patterns and Body Mass Index (BMI) status/central obesity. Results: The prevalence of general and central obesity was 9.5% and 53.4%. Traditional dietary pattern (high intake of rice, pork and vegetables) was inversely associated with general/central obesity; modern dietary pattern (high intake of fruit, fast food, and processed meat) was positively associated with general/central obesity. The highest quartile of traditional dietary pattern had a lower risk of general/central obesity compared with the lowest quartile, while an inverse picture was found for the modern dietary pattern. These associations were consistent by gender and urbanization levels. Conclusions: Dietary patterns are associated with general/central obesity in older Chinese. This study reinforces the importance of a healthy diet in promoting healthy ageing in China.
Background: As a public health emergency of international concern, the COVID-19 outbreak has had a tremendous impact on patients' psychological health. However, studies on psychological interventions in patients with COVID-19 are relatively rare.Objectives: This study examined the effectiveness of Cognitive Behavioral Therapy (CBT) in relieving patients' psychological distress during the COVID-19 epidemic.Methods: Ninety-three eligible participants selected by cluster sampling were randomized to an intervention group (N = 47) and a control group (N = 46). Participants in the control group received routine treatment according to the Chinese Management Guidelines for COVID-19, while participants in the intervention group received routine treatment with additional CBT. The Chinese Version of Depression Anxiety and Stress Scale-21 (DASS-21) was used to evaluate depression, anxiety, and stress for all participants at baseline and post-intervention. Two-sided t-test, and proportion tests were used to examine the differences between the intervention and control group for each DASS-21 indicator. Univariate linear regression was used to examine the association between chronic disease status and change in each DASS-21 indicator after intervention. Two-way scatter plots were generated to show the association of the length of hospital stay and the changes of each DASS-21 indicator by intervention and control groups.Results: Significant decreases in means were found for scales of depression, anxiety, stress and total DASS-21 in both intervention (p < 0.001) and control group (p = 0.001), with participants in the intervention group having a bigger reduction in means. After the intervention, more participants in the intervention group had no depression or anxiety symptoms than in the control group, but no statistical differences were found (p > 0.05). Compared with participants with chronic disease, participants with no chronic disease had a significantly larger reduction of total DASS-21 scale (coefficient = −4.74, 95% CI: −9.31; −0.17).The length of hospital stay was significantly associated with a greater increase in anxiety scale in the intervention group (p = 0.005), whilst no significant association was found in the control group (p = 0.29).Li et al. Psychological Intervention on COVID-19 PatientsConclusions: The patients with COVID-19 experienced high levels of anxiety, depression and stress. Our study result highlights the effectiveness of CBT in improving the psychological health among patients with COVID-19, also suggests that CBT should be focused on patients with chronic disease and those who have longer hospital stays. These results have important implications in clinical practice in improving psychological health in the context of COVID-19 pandemic. Trial Registration: ISRCTN68675756. Available at: http://www.isrctn.com/ ISRCTN68675756.
Aims To evaluate psychological well‐being and factors associated with post‐traumatic stress disorder (PTSD) among front‐line nurses during the coronavirus disease‐2019 (COVID‐19) pandemic. Background Coronavirus disease‐2019 is a pandemic that has posed a public health emergency of international concern. Psychological well‐being of front‐line nurses is a big concern during the COVID‐19 pandemic. Methods With a predictive study design, a same survey was sent separately at two time points (i.e. before and after nurses worked at COVID‐19 units) between January and March 2020 among 356 front‐line nurses in First Affiliated Hospital of Bengbu Medical College, Anhui, China. Results Of a total 356 front‐line nurses, stress level and the prevalence of PTSD were significantly increased after they worked at COVID‐19 units. Nurses who had work experience less than 2 years were significantly associated with a high risk of developing PTSD. Nurses who worked in COVID‐19 inpatients wards had significantly higher odds of being PTSD (odds ratio [OR] = 21.9, 95% confidence interval [CI]: 5.08; 94.5) than those who worked in other COVID‐19‐related units. Resilience was negatively associated with PTSD (OR = 0.96, 95% CI: 0.93; 0.99). Conclusion Nurses had significantly increased risk to develop PTSD during COVID‐19 pandemic. Implications for nursing management Clinical and policy strategies to support front‐line nurses’ psychological well‐being, particularly young nurses, in response to COVID‐19 crisis are urgently needed.
Paclitaxel is a first-line chemotherapeutic agent for gastric cancer; however, resistance limits its effectiveness. Investigation into the underlying mechanisms of paclitaxel resistance is urgently required. In the present study, a paclitaxel-resistant gastric cancer cell line (MGC-803R) was generated with a morphological phenotype of epithelial-to-mesenchymal transition (EMT) and increased expression levels of microRNA (miR)-155-5p. MGC-803R cell-derived exosomes were effectively taken up by paclitaxel-sensitive MGC-803S cells, which exhibited EMT and chemoresistance phenotypes. miR-155-5p was enriched in MGC-803R-exosomes and could be delivered into MGC-803S cells. miR-155-5p overexpression in MGC-803S cells via transfection with mimics resulted in similar phenotypic effects as treatment with MGC-803R exosome and increased miR-155-5p content in MGC-803S exosomes, which then capable of inducing the malignant phenotype in the sensitive cells. GATA binding protein 3 (GATA3) and tumor protein p53-inducible nuclear protein 1 (TP53INP1) were identified as targets of miR-155-5p. Exosomal miR-155-5p inhibited these targets by directly targeting their 3′ untranslated regions. Knockdown of miR-155-5p was observed to reverse the EMT and chemoresistant phenotypes of MGC-803R cells, potentially via GATA3 and TP53INP1 upregulation, which inhibited MGC-803R-exosomes from inducing the malignant phenotype. These results demonstrated that exosomal delivery of miR-155-5p may induce EMT and chemoresistant phenotypes from paclitaxel-resistant gastric cancer cells to the sensitive cells, which may be mediated by GATA3 and TP53INP1 suppression. Targeting miR-155-5p may thus be a promising strategy to overcome paclitaxel resistance in gastric cancer.
BackgroundIn Kenya, skilled attendance at delivery is well below the international target of 90% and the maternal mortality ratio is high at 362 (CI 254–471) per 100,000 live births despite various interventions. The preventative role of skilled attendance at delivery makes it a benchmark indicator for safe motherhood.MethodsMaternal health data from the Service Provision Assessment Survey, a subset of the 2010 Kenya Demographic Health Survey was analyzed. Logistic regression models were employed using likelihood ratio test to explore association between choice of skilled attendance and predictor variables.ResultsOverall, 94.8% of women are likely to seek skilled attendance at delivery. Cost, education level, number of antenatal visits and sex of provider were strongly associated with client’s intention to deliver with a skilled birth attendant at delivery. Women who reported having enough money set aside for delivery were 4.34 (p < 0.002, 95% CI: 1.73; 10.87) times more likely to seek skilled attendance. Those with primary education and above were 6.6 times more likely to seek skilled attendance than those with no formal education (p < 0.001, 95% CI: 3.66; 11.95). Women with four or more antenatal visits were 5.95 (p < 0.018, 95% CI: 1.35; 26.18) times more likely to seek skilled attendance. Compared to men, female providers impacted more on the client’s plan (OR = 2.02 (p < 0.014, 95% CI: 1.35; 3.53).ConclusionInterventions aimed at improving skilled attendance at delivery should include promotion of formal education of women and financial preparation for delivery. Whenever circumstances permit, women should be allowed to choose gender of preferred professional attendant at delivery.
The prevalence of successful aging is low among Chinese older people, and is affected by sociodemographic factors, such as education, Hukou and regions. Geriatr Gerontol Int 2017; 17: 1183-1190.
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