Group 2 innate lymphoid cells (ILC2s) reside in multiple organs in the body, where they play roles in immunity, tissue homeostasis, and metabolic regulation. However, little is known about the ...regulatory mechanisms of ILC2s in different organs. Here, we identified ILC2s in the mouse uterus and found that they express cell surface molecules, including the IL-33 receptor, ST2, that are roughly comparable to those expressed by lung ILC2s. Both in vivo and in vitro treatment with IL-33 induced type 2 cytokine production in uterine ILC2s, suggesting that they respond to IL-33 in a manner similar to ILC2s in other organs. Importantly, uterine ILC2s were nearly absent in ovariectomized mice and were increased in wild-type mice by estrogen administration, whereas lung ILC2s were unaffected by both ovariectomy and estrogen administration. Likewise, a marked reduction in uterine ILC2s was observed in mice deficient in estrogen receptor α or estrogen receptor β. Furthermore, uterine ILC2s highly expressed estrogen receptor α, and in vitro culture of isolated uterine ILC2s with 17β-estradiol modified expression of a number of genes. Finally, an increased prevalence in neonatal mortality was observed in litters from dams lacking the IL-33 receptor, ST2. Taken together, our findings indicate that unlike lung IL2Cs, uterine ILC2s are regulated by female sex hormones, which may specialize them for specific physiological functions.
Most of the state governments in United States (U.S.) issued lockdown or business restrictions amid the COVID-19 pandemic in March 2020, which created a unique opportunity to evaluate the air quality ...response to reduced economic activities. Data acquired from 28 long-term air quality stations across the U.S. revealed widespread but nonuniform reductions of nitrogen dioxide (NO2) and carbon monoxide (CO) during the first phase of lockdown (March 15–April 25, 2020) relative to a pre-lockdown reference period and historical baselines established in 2017–2019. The reductions, up to 49% for NO2 and 37% for CO, are statistically significant at two thirds of the sites and tend to increase with local population density. Significant reductions of particulate matter (PM2.5 and PM10) only occurred in the Northeast and California/Nevada metropolises where NO2 declined the most, while the changes in ozone (O3) were mixed and relatively minor. These findings are consistent with lower transportation and utility demands that dominate NO2 and CO emissions, especially in major urban areas, due to the lockdown. This study provides an insight into potential public health benefits with more aggressive air quality management, which should be factored into strategies to reopen the U.S. and global economy.
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•The lockdown issued due to COVID-19 had nonuniformly impacted air quality in the US.•Consistent NO2 and CO declines corroborate with low transportation/utility demands.•Reductions in NO2 ranged 5–49% and tended to increase with local population density.•Significant PM reductions only occurred where NO2 declined the most.•The impact on O3 was mixed, generally within ±20%.
Fluoroquinolones have been associated with collagen degradation, raising safety concerns related to more serious collagen disorders with use of these antibiotics, including aortic aneurysm and ...dissection.
To examine the relationship between fluoroquinolone therapy and the risk of developing aortic aneurysm and dissection.
We conducted a nested case-control analysis of 1477 case patients and 147 700 matched control cases from Taiwan's National Health Insurance Research Database (NHIRD) from among 1 million individuals longitudinally observed from January 2000 through December 2011. Cases patients were defined as those hospitalized for aortic aneurysm or dissection. One hundred control patients were matched for each case based on age and sex.
Current, past, or any prior-year use of fluoroquinolone. Current use was defined as a filled fluoroquinolone prescription within 60 days of the aortic aneurysm or dissection; past use refers to a filled fluoroquinolone prescription between 61 and 365 days prior to the aortic aneurysm; and any prior-year use refers to having a fluoroquinolone prescription filled for 3 or more days any time during the 1-year period before the aortic aneurysm or dissection.
Risk of developing aortic aneurysm or dissection.
A total of 1477 individuals who experienced aortic aneurysm or dissection were matched to 147 700 controls. After propensity score adjustment, current use of fluoroquinolones was found to be associated with increased risk for aortic aneurysm or dissection (rate ratio RR, 2.43; 95% CI, 1.83-3.22), as was past use, although this risk was attenuated (RR, 1.48; 95% CI, 1.18-1.86). Sensitivity analysis focusing on aortic aneurysm and dissection requiring surgery also demonstrated an increased risk associated with current fluoroquinolone use, but the increase was not statistically significant (propensity score-adjusted RR, 2.15; 95% CI, 0.97-4.60).
Use of fluoroquinolones was associated with an increased risk of aortic aneurysm and dissection. While these were rare events, physicians should be aware of this possible drug safety risk associated with fluoroquinolone therapy.
Nano-flow liquid chromatography tandem mass spectrometry (nano-flow LC-MS/MS) is the mainstay in proteome research because of its excellent sensitivity but often comes at the expense of robustness. ...Here we show that micro-flow LC-MS/MS using a 1 × 150 mm column shows excellent reproducibility of chromatographic retention time (<0.3% coefficient of variation, CV) and protein quantification (<7.5% CV) using data from >2000 samples of human cell lines, tissues and body fluids. Deep proteome analysis identifies >9000 proteins and >120,000 peptides in 16 h and sample multiplexing using tandem mass tags increases throughput to 11 proteomes in 16 h. The system identifies >30,000 phosphopeptides in 12 h and protein-protein or protein-drug interaction experiments can be analyzed in 20 min per sample. We show that the same column can be used to analyze >7500 samples without apparent loss of performance. This study demonstrates that micro-flow LC-MS/MS is suitable for a broad range of proteomic applications.
Both the size of the older population and the use of complementary and alternative medicine are increasing worldwide. This study evaluated the long-term trend in utilization of traditional Chinese ...medicine (TCM) and associated factors among older people in Taiwan.
Using the database of population-based interview surveys, we evaluated the one-month prevalence of TCM use among 13,945 older people aged over 65 years from 2001-2017. The sociodemographic status and medical comorbidities of older people who did and did not use TCM were compared by calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs) in the multiple logistic regressions.
The one-month prevalence of TCM use increased from 5.5% in 2001 to 9.1% in 2017 among older people in Taiwan. Overall, 7.3% of older people had used TCM within the previous month. People with a history of heart disease (OR 1.62, 95% CI 1.24-2.12), use of folk therapy (OR 3.16, 95% CI 2.00-4.99), and purchase of non-prescribed Chinese herbal medicine (OR 2.08, 95% CI 1.48-2.91) were more likely to use TCM than the comparison group. However, age ≥80 years (OR 0.48, 95% CI 0.31-0.72) and previous hospitalization (OR 0.59, 95% CI 0.41-0.85) were associated with the reduced use of TCM.
From 2001-2017, the use of TCM increased in the older population in Taiwan. The use of folk medicine and purchase of non-prescribed Chinese herbal medicine were significant predictors for the use of TCM.
Myocardial infarction is the leading cause of death worldwide. Restoration of blood flow rescues myocardium but also causes ischemia-reperfusion injury. Here, we show that in a mouse model of chronic ...neuropathic pain, ischemia-reperfusion injury following myocardial infarction is reduced, and this cardioprotection is induced via an anterior nucleus of paraventricular thalamus (PVA)-dependent parasympathetic pathway. Pharmacological inhibition of extracellular signal-regulated kinase activation in the PVA abolishes neuropathic pain-induced cardioprotection, whereas activation of PVA neurons pharmacologically, or optogenetic stimulation, is sufficient to induce cardioprotection. Furthermore, neuropathic injury and optogenetic stimulation of PVA neurons reduce the heart rate. These results suggest that the parasympathetic nerve is responsible for this unexpected cardioprotective effect of chronic neuropathic pain in mice.Various forms of preconditioning can prevent ischemic-reperfusion injury after myocardial infarction. Here, the authors show that in mice, the presence of chronic neuropathic pain can have a cardioprotective effect, and that this is dependent on neural activation in the paraventricular thalamus.
Chronic pain is often accompanied by anxiety and depression disorders. Amygdala nuclei play important roles in emotional responses, fear, depression, anxiety, and pain modulation. The exact mechanism ...of how amygdala neurons are involved in pain and anxiety is not completely understood. The central nucleus of the amygdala contains 2 major subpopulations of GABAergic neurons that express somatostatin (SOM+) or protein kinase Cδ (PKCδ+). In this study, we found about 70% of phosphorylated ERK-positive neurons colocalized with PKCδ+ neurons in the formalin-induced pain model in mice. Optogenetic activation of PKCδ+ neurons was sufficient to induce mechanical hyperalgesia without changing anxiety-like behavior in naïve mice. Conversely, chemogenetic inhibition of PKCδ+ neurons significantly reduced the mechanical hyperalgesia in the pain model. By contrast, optogenetic inhibition of SOM+ neurons induced mechanical hyperalgesia in naïve mice and increased phosphorylated ERK-positive neurons mainly in PKCδ+ neurons. Optogenetic activation of SOM+ neurons slightly reduced the mechanical hyperalgesia in the pain model but did not change the mechanical sensitivity in naïve mice. Instead, it induced anxiety-like behavior. Our results suggest that the PKCδ+ and SOM+ neurons in the central amygdala exert different functions in regulating pain-like and anxiety-like behaviors in mice.
Colonoscopy screening and colonoscopic polypectomy can decrease the incidence and mortality rate of colorectal cancer (CRC). The adenoma detection rate and accuracy of diagnosis of colorectal polyp ...which vary in different experienced endoscopists have impact on the colonoscopy protection effect of CRC. The work proposed a colorectal polyp image detection and classification system through grayscale images and deep learning. The system collected the data of CVC-Clinic and 1000 colorectal polyp images of Linkou Chang Gung Medical Hospital. The red-green-blue (RGB) images were transformed to 0 to 255 grayscale images. Polyp detection and classification were performed by convolutional neural network (CNN) model. Data for polyp detection was divided into five groups and tested by 5-fold validation. The accuracy of polyp detection was 95.1% for grayscale images which is higher than 94.1% for RGB and narrow-band images. The diagnostic accuracy, precision and recall rates were 82.8%, 82.5% and 95.2% for narrow-band images, respectively. The experimental results show that grayscale images achieve an equivalent or even higher accuracy of polyp detection than RGB images for lightweight computation. It is also found that the accuracy of polyp detection and classification is dramatically decrease when the size of polyp images small than 1600 pixels. It is recommended that clinicians could adjust the distance between the lens and polyps appropriately to enhance the system performance when conducting computer-assisted colorectal polyp analysis.
Background Airway exposure to environmental antigens generally leads to immunologic tolerance. A fundamental question remains: Why is airway tolerance compromised in patients with allergic airway ...diseases? IL-33 promotes innate and adaptive type 2 immunity and might provide the answer to this question. Objective The goal of this study was to investigate the roles played by IL-33 in altering regulatory T (Treg) cells in the lungs and in affecting previously established airway immunologic tolerance. Methods We analyzed CD4+ forkhead box P3 (Foxp3)+ Treg cells that were isolated from the lungs of naive BALB/c mice and those treated with IL-33. Airway tolerance and allergen-induced airway inflammation models in mice were used to investigate how IL-33 affects established immunologic tolerance in vivo. Results CD4+ Foxp3+ Treg cells in the lungs expressed the IL-33 receptor ST2. When exposed to IL-33, Treg cells upregulated their expression of the canonical TH 2 transcription factor GATA3, as well as ST2, and produced type 2 cytokines. Treg cells lost their ability to suppress effector T cells in the presence of IL-33. Airway administration of IL-33 with an antigen impaired immunologic tolerance in the lungs that had been established by prior exposure to the antigen. Dysregulated Foxp3+ Treg cells with distinct characteristics of TH 2 cells increased in the lungs of mice undergoing IL-33–dependent allergen-driven airway inflammation. Conclusions IL-33 dysregulated lung Treg cells and impaired immunologic tolerance to inhaled antigens. Established airway tolerance might not be sustained in the presence of an innate immunologic stimulus, such as IL-33.
Acute diarrhea is a major cause of childhood morbidity and an economic burden for families. The aim of this study is to explore the effect of probiotics on clinical symptoms, intestinal microbiota, ...and inflammatory markers during childhood diarrhea.
Children (
= 81) aged six months to six years (mean age 2.31 years) hospitalized for acute diarrhea were randomized to receive probiotics (
variety
;
= 42) or no probiotics (
= 39) orally twice daily for seven days. Feces samples were also collected to evaluate microbial content using a traditional agar plate and next-generation sequencing. Immunoglobulin A (IgA), lactoferrin, and calprotectin were determined by enzyme-linked immunosorbent assay (ELISA) and compared in different groups. Other clinical symptoms or signs, including fever, vomiting, diarrhea, abdominal pain, bloated abdomen, daily intake, appetite, and body weight were also assessed.
Data were collected from 81 individuals across three different time points. Total fecal IgA levels in fecal extracts of the probiotics group were higher than those in the control group, reaching statistical significance (
0.05). Concentrations of fecal lactoferrin and calprotectin were significantly downregulated in patients with probiotic
variety
(Lc) consumption compared to those of the control (
0.05). Probiotic Lc administration may be beneficial for gut-microbiota modulation, as shown by the data collected at one week after enrollment. Counts of
and
species were elevated in stool culture of the probiotic group. Appetite and oral intake, body-weight gain, abdominal pain, bloating, as well as bowel habits (diarrhea) were much better in children receiving probiotics compared with those in the control group.
Fecal IgA increased during acute diarrhea under Lc treatment; in contrast, fecal lactoferrin and calprotectin were downregulated during acute diarrhea under Lc treatment. Probiotic Lc may be a useful supplement for application in children during acute diarrhea to reduce clinical severity and intestinal inflammatory reaction.
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