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Seven undescribed compounds, dentipellinones A‒D (1, 2, 5, and 6), dentipellinol (3), methoxyerinaceolactone B (4), and erinaceolactomer A (7), were isolated from the culture broth of Dentipellis fragilis. Chemical structures of these isolated compounds were determined by analyses of 1D and 2D-NMR and MS data in comparison with data reported in the literature. Absolute configurations of 1‒7 were also determined by Electronic Circular Dichroism calculations. The isolated compounds were evaluated for their anti-inflammatory effects on NO production and pro-inflammatory cytokines levels in LPS-stimulated RAW264.7 cells. Compounds 5 and 7 were evaluated for their anti-inflammatory effects on NO production and pro-inflammatory cytokine levels in LPS-stimulated RAW264.7 cells. They exhibited inhibitory effects on LPS-induced NO production in a dose-dependent manner, and significantly reduced the levels of inflammatory-related cytokines such as IL-1β and IL-6. TNF-α was not involved in the anti-inflammatory effects of these compounds. Finally, compounds 5 and 7 showed significant anti-inflammatory effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Molecular mechanisms underlying psychological sequelae of exposure to stressful experiences, such as posttraumatic stress disorder (PTSD) and depression, are not well understood., Methods: Using convergent evidence from animal and human transcriptomic and genomic studies, we aimed to identify genetic mechanisms underlying depression and anxiety after traumatic experiences., Results: From a transcriptome-wide analysis in mice, we found the Ppm1f gene to be differentially expressed in the amygdala and medial prefrontal cortex (mPFC) a week after immobilization stress. Next, we found that PPM1F messenger RNA levels in human blood were downregulated in cases with symptoms of comorbid PTSD and depression and consistently in cases with anxiety symptoms in a separate human dataset. Furthermore, we showed that a genetic variant of PPM1F, rs17759843, was associated with comorbid PTSD and depression and with PPM1F expression in both human brain and blood. Given prior reported mechanistic links between PPM1F and CAMK2 (CAMKII), we examined blood messenger RNA level of CAMK2G in humans and found it to be lower in cases with comorbid PTSD and depression. We also found that PPM1F protein levels and colocalization with CAMK2G were altered in amygdala and mPFC of male mice. Additionally, we found that a systemic dose of corticosterone blocked the depressive-like phenotype elicited by stress in female mice. Lastly, corticosterone rescued the anxiety-like phenotype and messenger RNA levels of Ppm1f in amygdala and mPFC in male mice and in mPFC of female mice., Conclusions: Taken together, our data suggest a mechanistic pathway involving PPM1F and CAMK2G in stress- and trauma-related manifestation of anxiety and depression across species., (Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

We estimated the exposure to ambient air pollutants and analyzed the associations with allergic diseases. We enrolled 177 children with atopic dermatitis (AD) and 70 asthmatic adults living in Seoul Metropolitan Area, Korea, and followed for 17months between August 2013 and December 2014. Parents or patients recorded symptom scores on a daily basis. Exposure to particulate matter with a diameter <10μm (PM 10 ) and nitrogen dioxide (NO 2 ) was estimated in four different ways in each individual, using the AQ1 (measurements from the nearest air quality monitoring station to residential houses), AQ2 (measurements modified from AQ1 with the indoor level of air pollutants and time activity of each individual), AQ1-DI, and AQ2-DI (measurements modified from AQ1 and AQ2, respectively, with daily inhalation intakes of air pollutants). A generalized linear mixed model (GLMM) was used to analyze the associations between exposure metrics and clinical symptoms after adjusting for ambient temperature and humidity, age, season, gender, and time trend. The exposure metrics for PM 10 and NO 2 showed different distributions. Symptoms of AD and asthma were positively associated with exposure to PM 10 , but not NO 2 , in all exposure metrics. The effect size of PM 10 exposure on asthma symptoms was slightly greater in metrics with inhalation capacity (AQ-DIs) than in those without (AQs). This pattern was not observed in AD. Exposure to PM 10 is associated with symptom aggravation in childhood AD and adult asthma. Different exposure estimates may be used to evaluate the impact of air pollution on different allergic diseases., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The current effective treatment options for posttraumatic stress disorder (PTSD) are limited, and therefore the need to explore new treatment strategies is critical. Pharmacological inhibition of the renin-angiotensin system is a common approach to treat hypertension, and emerging evidence highlights the importance of this pathway in stress and anxiety. A recent clinical study from our laboratory provides evidence supporting a role for the renin-angiotensin system in the regulation of the stress response in patients diagnosed with PTSD., Methods: With an animal model of PTSD and the selective angiotensin receptor type 1 (AT1) antagonist losartan, we investigated the acute and long-term effects of AT1 receptor inhibition on fear memory and baseline anxiety. After losartan treatment, we performed classical Pavlovian fear conditioning pairing auditory cues with footshocks and examined extinction behavior, gene expression changes in the brain, as well as neuroendocrine and cardiovascular responses., Results: After cued fear conditioning, both acute and 2-week administration of losartan enhanced the consolidation of extinction memory but had no effect on fear acquisition, baseline anxiety, blood pressure, and neuroendocrine stress measures. Gene expression changes in the brain were also altered in mice treated with losartan for 2 weeks, in particular reduced amygdala AT1 receptor and bed nucleus of the stria terminalis c-Fos messenger RNA levels., Conclusions: These data suggest that AT1 receptor antagonism enhances the extinction of fear memory and therefore might be a beneficial therapy for PTSD patients who have impairments in extinction of aversive memories., (Published by Elsevier Inc.)

Background: Nonasthmatic eosinophilic bronchitis (NAEB) is an important cause of chronic cough, and it can be diagnosed by an induced-sputum (IS) examination. However, an IS examination is a complex and time-consuming procedure, and it has limited clinical application. This study aimed to evaluate the role of exhaled nitric oxide (NO) for the investigation of chronic cough, especially of NAEB., Methods: Two hundred eleven nonsmoking patients with a cough lasting > 3 weeks were enrolled in the study. The patients were examined and investigated with conventional diagnostic tools, including an IS examination. Exhaled NO was measured by a chemoluminescent analyzer., Results: One hundred seventeen patients with adequate IS results were analyzed: asthma, n = 14; NAEB, n = 21; and "others," n = 82. Exhaled NO and IS eosinophils were significantly higher in the asthma group and NAEB group than in the others group. Exhaled NO and IS eosinophils were significantly correlated in the asthma and NAEB groups. In the nonasthmatic group, the sensitivity and specificity of exhaled NO for detecting NAEB, using 31.7 parts per billion as the exhaled NO cutoff point, were 86% and 76%, respectively. Positive and negative predictive values were 47% and 95%, respectively, and positive and negative likelihood ratios were 3.51 and 0.19, respectively., Conclusion: We concluded that exhaled NO measurement may be useful as part of the initial evaluation for chronic cough, especially for the exclusion of NAEB. A low level of exhaled NO suggested little likelihood of NAEB for the nonasthmatic patients with chronic cough.

Study Objectives: Cough lasting > 3 weeks has been defined as chronic cough. However, it might be more persuasive to divide cough into subacute, lasting 3 to 8 weeks, and chronic, lasting > 8 weeks. We evaluated the causes and clinical courses of subacute cough, and the value of the bronchoprovocation test and induced sputum examination (IS)., Methods: Nonsmoking patients with cough of 3 to 8 weeks duration were enrolled into the study. Patients with dyspnea, basal FEV1 of < 70% predicted, abnormal findings on a plain chest radiograph or physical examination were excluded. We prescribed an antihistamine-decongestant for patients who were suspected to have postinfectious cough or postnasal drip. If patients had positive results on a bronchoprovocation test or IS, therapy with inhaled corticosteroids was substituted according to an algorithmic approach., Results: One hundred eighty-four patients (77 men and 107 women) were evaluated; the mean age of the study group was 47.5 years. Eighty-nine of 184 patients had postinfectious cough. Cough resolved without treatment in 62 patients. Twenty-nine of 43 patients with positive bronchoprovocation test results had cough-variant asthma., Conclusions: Postinfectious cough was the most common cause of subacute cough. The spontaneous resolution of cough was frequent in patients with subacute cough. Unless asthma was strongly suspected, the performance of the bronchoprovocation test could be delayed until after empirical treatment had been administered.