We explored the regulation of filaggrin, cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) expression induced by urban particulate matter (PM) in human keratinocytes. In addition, we investigated the signaling pathways involved in PM-induced effects on COX2/PGE2 and filaggrin. PMs induced increases in COX2 expression and PGE2 production, and decreased filaggrin expression. These effects were attenuated by pretreatment with COX2 inhibitor and PGE2 receptor antagonist, or after transfection with siRNAs of the aryl hydrocarbon receptor (AhR), gp91phox and p47phox. Furthermore, PM-induced generation of reactive oxygen species (ROS) and NADPH oxidase activity was attenuated by pretreatment with an AhR antagonist (AhRI) or antioxidants. Moreover, Nox-dependent ROS generation led to phosphorylation of ERK1/2, p38, and JNK, which then activated the downstream molecules NF-κB and AP-1, respectively. In vivo studies in PMs-treated mice showed that AhRI and apocynin (a Nox2 inhibitor) had anti-inflammatory effects by decreasing COX2 and increasing filaggrin expression. Our results reveal for the first time that PMs-induced ROS generation is mediated through the AhR/p47 phox/NADPH oxidase pathway, which in turn activates ERK1/2, p38/NF-κB and JNK/AP-1, and which ultimately induces COX2 expression and filaggrin downregulation. Up-regulated expression of COX2 and production of PGE2 may lead to impairment of skin barrier function.
Transplant care teams should incorporate strategies that enhance self-efficacy, as proposed by social cognitive theory, into their care programmes for kidney transplant recipients. Interventions to maintain and improve patients' self-care behaviour should continue to be emphasized and facilitated. Support to enhance patients' problem-solving skills and the partnership of patients with health professionals is needed.
Methadone and buprenorphine are widely used for treating people with opioid dependence, including pregnant women. Prenatal exposure to opioids has devastating effects on the development of human fetuses and may induce long-term physical and neurobehavioral changes during postnatal maturation. This study aimed at comparing the behavioral outcomes of young rats prenatally exposed to buprenorphine, methadone, and morphine. Pregnant Sprague-Dawley rats were administered saline, morphine, methadone, and buprenorphine during embryonic days 3–20. The cognitive function, social interaction, anxiety-like behaviors, and locomotor activity of offsprings were examined by novel object recognition test, social interaction test, light–dark transition test, elevated plus-maze, and open-field test between 6 weeks and 10 weeks of age. Prenatal exposure to methadone and buprenorphine did not affect locomotor activity, but significantly impaired novel object recognition and social interaction in both male and female offsprings in the same manner as morphine. Although prenatal exposure to methadone or buprenorphine increased anxiety-like behaviors in the light–dark transition in both male and female offsprings, the effects were less pronounced as compared to that of morphine. Methadone affected elevated plus-maze in both sex, but buprenorphine only affected the female offsprings. These findings suggest that buprenorphine and methadone maintenance therapy for pregnant women, like morphine, produced detrimental effects on cognitive function and social behaviors, whereas the offsprings of such women might have a lower risk of developing anxiety disorders.
The aim of our study is to analyze the relationships between the characteristics of renal stones determined by unenhanced helical computed tomography (UHCT) and their outcomes after extracorporeal shock wave lithotripsy (ESWL) as well as to predict ESWL outcomes of renal stones by their UHCT characteristics with the use of multivariate analysis. During a 7-month period, 80 adult patients with renal stones underwent ESWL as well as UHCT both before and 3 months after ESWL. Of the 80 patients, 42 patients were classified as ESWL successes and 38 as ESWL failures based on their post-ESWL UHCT findings. For pre-ESWL UHCT, a stone number of more than 2 (P=0.0236), a maximal stone size of greater than 12 mm (P<0.0001), a stone burden of more than 700 mm3 (P<0.0001), a maximal stone density of more than 900 HU (P=0.0008) and nonround/oval stones (P=0.0007) were associated with ESWL failure outcomes. Multivariate analysis demonstrated that a stone burden of more than 700 mm3 (P=0.0003), the presence of nonround/oval stones (P=0.0072) and a maximal stone density of more than 900 HU (P=0.0430) were statistically significant predictors of a failure outcome for ESWL. Thus, the analysis of stone characteristics of renal stones by UHCT is helpful in selecting appropriate patients undergoing ESWL for favorable outcomes and reduces the overall costs of the treatment of renal stones.
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