ABSTRACT
Congenital heart defects (CHDs) are congenital abnormalities involving the gross structures of the heart and large blood vessels. Environmental factors, genetic factors and their interactions may contribute to the pathogenesis of CHDs. Generally, trace elements can be classified into essential trace elements and non-essential trace elements. Essential trace elements such as copper (Cu), zinc (Zn), iron (Fe), selenium (Se), and manganese (Mn) play important roles in human biological functions such as metabolic function, oxidative stress regulation, and embryonic development. Non-essential trace elements such as cadmium (Cd), arsenic (As), lead (Pb), nickle (Ni), barium (Ba), chromium (Cr) and mercury (Hg) are harmful to health even at low concentrations. Recent studies have revealed the potential involvement of these trace elements in the pathogenesis of CHDs. In this review, we summarized current studies exploring exposure to essential and non-essential trace elements and risks of CHDs, in order to provide further insights for the pathogenesis and prevention of CHDs.
ABSTRACT
A series of oxazolopyrimidine-based ureas and amides were designed, synthesized, and biologically evaluated for their antiproliferative and antiangiogenic activities. These compounds were identified to exhibit inhibitory activities against human umbilical vein endothelial cells (HUVEC) in vitro. Among these compounds, compound 22 effectively inhibited the migration and capillary-like tube formation of human umbilical vein endothelial cells. It also exhibited a concentration-dependent inhibition on capillary sprouting from the rat aorta rings. Preliminary mechanistic studies revealed that compound 22 suppressed protein kinases activation, by decreasing PI3K and ERK 1/2 phosphorylation. These results support the further investigation of this class of compounds as potential anticancer agents.
Subject(s)
Amides/pharmacology , Angiogenesis Inhibitors/chemistry , Angiogenesis Inhibitors/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Oxazoles/pharmacology , Protein Kinase Inhibitors/pharmacology , Protein Kinases/metabolism , Pyrimidines/pharmacology , Urea/pharmacology , Amides/chemical synthesis , Amides/chemistry , Angiogenesis Inhibitors/chemical synthesis , Animals , Aorta/drug effects , Capillaries/drug effects , Cell Movement/drug effects , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Humans , Molecular Structure , Oxazoles/chemistry , Phosphorylation/drug effects , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Pyrimidines/chemistry , Rats , Structure-Activity Relationship , Urea/analogs & derivatives , Urea/chemistryABSTRACT
Tumor angiogenesis is mediated by vascular endothelial growth factor receptor (VEGFR) and other protein kinases. Inhibition of these kinases presents an attractive approach for developing anticancer therapeutics. In this work, a series of 2,5,7-trisubstituted oxazolo[5,4-d]pyrimidines were synthesized, and their inhibitory activities were investigated against VEGFR-2 and human umbilical vein endothelial cells (HUVEC) in vitro. Compound 9n exhibited the most potent inhibitory activity with IC50 values of 0.33 and 0.29â µM for VEGFR-2â kinase and HUVEC, respectively. A further kinase selectivity assay revealed that these compounds exhibit good VEGFR and moderate EGFR inhibitory activities. Docking analysis suggested a common mode of interaction at the ATP-binding site of VEGFR-2.
Subject(s)
Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors , Adenosine Triphosphate/metabolism , Binding Sites , Cell Proliferation/drug effects , Chemistry Techniques, Synthetic , Drug Evaluation, Preclinical/methods , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Inhibitory Concentration 50 , Molecular Docking Simulation , Protein Kinase Inhibitors/chemical synthesis , Pyrimidines/chemistry , Structure-Activity Relationship , Vascular Endothelial Growth Factor Receptor-2/metabolismABSTRACT
AIMS: The aim of this study was to examine the prevalence of psychological distress in survivors aged 60 years old and older by sex and analyse risk factors for psychological distress in male and female older survivors 2 years after the Wenchuan earthquake. METHODS: This was a cross-sectional study. Two hundred and fifty-seven older people were involved and a multistage random sampling method was utilised. Logistic regression analysis was used to determine risk factors for psychological distress among older men and women. RESULTS: A higher prevalence of psychological distress was observed in older women than in older men. Loss of family members and displacement from pre-earthquake residence were significant risk factors for psychological distress in older men. Significant risk factors for psychological distress in older women were low educational level, chronic diseases, loss of family members, and displacement from original residence. CONCLUSIONS: Health-care providers should develop gender-based strategies to improve mental health among older survivors in a long-term post-disaster recovery programme.
Subject(s)
Aging/psychology , Earthquakes , Stress, Psychological/epidemiology , Survivors/psychology , Adaptation, Psychological , Age Factors , Aged , Attitude to Death , Chi-Square Distribution , China/epidemiology , Chronic Disease , Comorbidity , Cross-Sectional Studies , Educational Status , Female , Humans , Logistic Models , Male , Middle Aged , Odds Ratio , Prevalence , Residence Characteristics , Risk Factors , Sex Factors , Stress, Psychological/diagnosis , Stress, Psychological/psychology , Time FactorsABSTRACT
BACKGROUND: Nurses are often called upon to play the role of first responder when disaster occurs. Yet the lack of accepted competencies and gaps in education make it difficult to recruit nurses prepared to respond to a disaster and provide assistance in an effective manner. DESIGN: Based on the International Council of Nurses (ICN) Framework of Disaster Nursing Competencies and Global Standards for the Initial Education of Professional Nurses and Midwives, a training course titled "Introduction to Disaster Nursing" was designed and implemented with 150 students. A pre-post survey design was used to assess changes in participants' self-rated disaster nursing competencies. The impact of the training course on participants' attitudes toward disaster nursing and their learning experience were also assessed. FINDINGS: All participants passed the assessments and examination with an average score of 70%. Pre- and posttraining self-ratings of the disaster nursing competencies increased from 2.09 to 3.71 (p < .001) on a Likert scale of 1 to 5, and the effect size was large, with Cohen's d higher than 0.8. No significant difference in both examination results (60% group assignments; 40% written examination) and self-rated competencies was noted between the senior year students and graduate nurse participants by Mann-Whitney U test (p value = .90). The majority of participants indicated their willingness to participate as a helper in disaster relief and saw themselves competent to work under supervision. CONCLUSIONS: The ICN Framework of Disaster Nursing Competencies was instrumental to guide the training curriculum development. This introductory training course could be incorporated into undergraduate nursing education programs as well as serve as a continuing education program for graduate nurses. CLINICAL RELEVANCE: The training program can be used for preparing generalist nurses of their nursing competencies in disaster preparedness, response and post-disaster recovery and rehabilitation.
