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ICA inhibited H/R-induced ferroptosis and oxidative stress in cardiomyocytes. Erastin treatment reversed the inhibitory effect of ICA on ferroptosis in H/R cells. The expression of Nrf2 and HO-1 in H/R-induced H9C2 cells was reduced, while ICA treatment reversed this trend. Inhibition of the Nrf2/HO-1 pathway reversed the protective effect of ICA on H/R-induced ferroptosis. Collectively, our results suggest that ICA attenuates H/R-induced ferroptosis of cardiomyocytes by activating the Nrf2/HO-1 signaling pathway.Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are small molecules that directly impact the CFTR protein, improving the function of the CFTR chloride and bicarbonate channel. Beginning in 2012 with the Food and Drug Administration approval of the first CFTR modulator, ivacaftor, this class of medications has had largely positive effects on many outcomes in people with cystic fibrosis (PwCF), including lung function, growth, and other clinical parameters. There have been continued exciting developments in the current research on CFTR modulators, expanding beyond original studies. This first part of a three-part cystic fibrosis (CF) year in review 2020 will focus on research on CFTR modulators. In addition to reviewing new clinical insights, we describe work done on novel outcomes, adverse effects, issues related to cost, and next steps for clinical trials. The review focuses on articles from Pediatric Pulmonology published in 2020, but it includes articles from other journals that are of particular interest to clinicians. New developments in CF research continue to be brought forth to the CF community, deepening the understanding of this disease and improving clinical care.
The elevated expression of interleukin-6 (IL-6) in patients with interstitial cystitis/bladder painful syndrome (IC/BPS) has been demonstrated, but the role of IL-6 in IC/BPS and its source remain to be explored.
IC/BPS rat model was created in female rats by using long-term intermittent intravesical hyaluronidase (0.5 ml, 4 mg/ml). After modeling, IL-6 stimulation group, and anti-IL-6R group were treated with recombinant rat IL-6 and tocilizumab, respectively. Symptomatic changes were detected by Vonfrey pain score and urodynamics, and hematoxylin-eosin (HE) staining, mast cell staining and Masson staining were used to evaluate the changes of inflammation in the bladder tissue of rats. Cell sources of IL-6 was explored through enzyme linked immunosorbent assay (ELISA) test, reverse transcription polymerase chain reaction (RT-PCR), and western-blot test on the supernatant of coculturing rat bladder epithelial cells and rat macrophages.
The Vonfrey pain scores of the model group and IL-6 stimulation groued an essential role in the development of IC/BPS rat model as a proinflammation cytokine. Further evidence from coculture proved that macrophages are the cell resource of IL-6 in IC/BPS.
The use of electronic cigarettes (e-cigarettes) among adolescents is increasing worldwide. E-cigarettes are marketed as a safe alternative to other tobacco products. The aim of this systematic review is to evaluate whether e-cigarette use in children and adolescents is associated with coughing.
Studies were identified through systematic searches of Excerpta Medica Database, Medline, Cumulative Index to Nursing and Allied Health Literature, British Nursing Index, OVID Emcare, Health Management Information Consortium, PsycINFO, and Allied and Complementary Medicine. The Grey Literature was also searched. Selected studies either contained only children and adolescents as study participants or if adults were included, the data for adolescents and children must be presented separately.
Seven studies were selected from 104. Three studies compared e-cigarette users with nonusers; two studies found a significant association between coughing and e-cigarette use in adolescence. Two studies investigated whether adolescents attributed their symptoms to their e-cigarette use. One study reported that coughing was the most likely negative symptom reported by adolescents on initiation of e-cigarette use; the other study found that adolescents, on initiation of e-cigarette use, reported coughing. Two studies looked at the cases of children and adolescents who had presented to the hospital after e-cigarette use and found coughing was a common presenting symptom.
This systematic review shows that adolescent use of e-cigarettes is associated with increased coughing and e-cigarette users are more likely to report coughing compared to non-users.
This systematic review shows that adolescent use of e-cigarettes is associated with increased coughing and e-cigarette users are more likely to report coughing compared to non-users.
To evaluate the impact of human milk and different neonatal variables on tidal breathing flow-volume loop (TBFVL) parameters within three months' corrected age (CA) in infants born ≤32 wks or weighing <1500 g.
We retrospectively studied 121 infants with gestational age (GA) ≤ 32 weeks or birth weight (BW) <1500 gr who had lung function assessment within three months' CA by TBFVL analysis between June 2009 and April 2018. We investigated the impact of GA, gender, being Small for GA (SGA), sepsis, days of mechanical ventilation (MV) and human milk feeding (HMF) on later respiratory function, both in the entire group and according to BW ( ≤1000 g and >1000 g).
The mean(SD) z-score for tidal volume (Vt) and time to peak expiratory flow to expiratory time (tPTEF/tE) were respectively -4.3 (2.5) and -0.8 (2.0) for the overall population with no significant differences between infants <1000 g or ≥1000 g. The mean(SD) Vt standardized for body weight was 6.2(2.0) ml/kg. Being female was associated with better Vt/Kg, whereas longer MV or being born SGA were associated with worst tPTEF/tE. For infants with BW < 1000 gr, tPTEF/tE was positively associated with HMF.
An early TBFVL assessment within three months' CA already reveals lung function alteration in preterm infants. Being female is associated with better Vt/Kg, while longer duration of MV or being born SGA negatively affect tPTEF/tE. The positive association between HMF and better tPTEF/tE in infants with BW <1000 g has emerged, which deserves further investigation.
An early TBFVL assessment within three months' CA already reveals lung function alteration in preterm infants. Being female is associated with better Vt/Kg, while longer duration of MV or being born SGA negatively affect tPTEF/tE. The positive association between HMF and better tPTEF/tE in infants with BW less then 1000 g has emerged, which deserves further investigation.
Bronchial challenge test (BCT) measures current airways-hyperreactivity, however, its predictive role in pre-school children (<6 years) for the diagnosis of asthma at school age is still debatable. We aimed to find whether preschool children with a positive adenosine or methacholine BCT are more prone to asthma at school age.
We included children aged 6-13 years with respiratory symptoms that were previously referred to our pulmonary function laboratory for BCT (methacholine or adenosine, depending on the question asked) at age 10 months to 6 years (baseline). BCT was considered positive based on spirometry results or wheezing, desaturation, and tachypnea reactions. The primaryoutcome measure was asthma diagnosis at school age using the well-validated International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. We used logistic regression analysis to explore whether positive BCT could predict school-age asthma while including age and collected modified asthma predictive indexin the model.
One hundred and fifty-one of 189 children (53% males), completed the ISAAC questionnaire (response rate = 80%). Mean ages at BCT and at follow-up were 3.9 ± 1.28 and 9.4 ± 1.85 years, respectively. At baseline, 40 of 67 had a positive adenosine test and 73 of 84 had a positive methacholine BCT. Thirty-nine children were diagnosed with asthma at school age. Logistic regression analysis showed that a positive adenosine test at pre-school age was the best predictor, significantly increasing the odds of asthma at school age by 6.34 (95% CI 1.23-32.81, p = .028), while methacholine did not show significance (p = .69).
Choosing the relevant BCT for the question asked, positive adenosine, but not methacholine test, at pre-school, may predict asthma at school age.
Choosing the relevant BCT for the question asked, positive adenosine, but not methacholine test, at pre-school, may predict asthma at school age.Concerns were raised regarding the role feed and feed ingredients play for risk of disease introduction and dissemination after PEDV was first identified mid-2013. Subsequently there has been a body of research and reviews completed. The results suggest a subset of contaminated feed ingredients could serve as vehicles for transboundary disease introduction into the United States. That has led to the development of biosecurity information from the pork and feed industry associations. At this time, implementation is voluntary. In 2019, representatives from pork producers, veterinarians, pork and other agriculture commodity associations and animal food industry associations formed a feed safety task force. The United States Department of Agriculture, the United States Food and Drug Administration and the Canadian Food Inspection Agency were also invited and attended. The task force operates under the premise that all participants agree there is risk of introduction of pathogens into and within the US via imported feed products. It is agreed that any actions should be achievable, are based on science and should minimize trade disruptions. The pork and feed industries have the same goal - a healthy, productive US swine herd. While our two industry sectors may have different ideas on how to prevent the introduction of diseases via imported feed ingredients, there is agreement that the general foundation for these approaches must be science based, cost effective and minimize negative impacts on market and international trade. Noncompliance with voluntary mitigation measures puts the entire pork industry at risk, all allied industries, and the US agricultural economy in general. selleck chemicals llc Because of that it is essential to continue to evaluate the role of effective regulation to ensure risk of introduction is minimized through implementation of programs that will be broadly and uniformly applied.c-Kit overexpression and activating mutations, which are reported in various cancers, including gastrointestinal stromal tumor (GIST), small-cell lung cancer (SCLC), acute myeloid leukemia, acral melanoma, and systemic mastocytosis (SM), confer resistance to tyrosine kinase inhibitors (TKIs). To overcome TKI resistance, an anti-c-Kit antibody-drug conjugate was developed in this study to treat wild-type and mutant c-Kit-positive cancers. NN2101, a fully human IgG1, was conjugated to DM1, a microtubule inhibitor, through N-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) (to give NN2101-DM1). The antitumor activity of NN2101-DM1 was evaluated in vitro and in vivo using various cancer cell lines. NN2101-DM1 exhibited potent growth-inhibitory activities against c-Kit-positive cancer cell lines. In a mouse xenograft model, NN2101-DM1 exhibited potent growth-inhibitory activities against imatinib-resistant GIST and SM cells. In addition, NN2101-DM1 exhibited a significantly higher anti-cancer effect than carboplatin/etoposide against SCLC cells where c-Kit does not mediate cancer pathogenesis.