bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysregulation of BMP9/BMPR2/SMAD signalling pathway contributes to pulmonary fibrosis and pulmonary hypertension induced by bleomycin in rats
Authors: Jiang Qian , Liu Chunli , Liu Shiyun , Lu Wenju , Li Yi , Luo Xiaoyun , Ma Ran , Zhang Chenting , Chen Haixia , Chen Yuqin , Zhang Zizhou , Hong Cheng , Guo Wenliang , Wang Tao , Yang Kai , Wang Jian 
Published: October 2020

Background and PurposePulmonary hypertension related to pulmonary fibrosis is classed as WHO Group III, one of the most common groups which lacks effective treatment options. In this study, we aimed to uncover the underlying mechanisms, particularly the involvement of the BMP9/BMPR2/SMAD signalling pathway, in this subtype of pulmonary hypertension.Experimental ApproachMale Sprague Dawley rats were used to establish a model of pulmonary hypertension with pulmonary fibrosis, induced by bleomycin. Haemodynamic and lung functions were measured, along with histological and immunohistochemical examinations. Primary cultures of rat pulmonary microvascular endothelial cells (PMVECs) were analysed with western blots, apoptosis assays and immunohistochemistry.Key ResultsEarly (7 days) after bleomycin treatment of rats, pulmonary arterial thickening and severe loss of pulmonary arterial endothelium were observed, followed (14 days) by increased right ventricular systolic pressure and right ventricular hypertrophy. Marked down‐regulation of the BMP9/BMPR2/SMAD signalling pathway was markedly down‐regulated in lung tissues from bleomycin‐treated rats (throughout the 7‐ to 35‐day treatment period) and bleomycin‐treated rat PMVECs, along with excessive cell apoptosis and loss of pulmonary arterial endothelium. Treatment with recombinant human bone morphogenetic protein 9 (rhBMP9) attenuated these aspects of bleomycin‐induced pulmonary hypertension, by restoring disrupted BMP9/BMPR2/SMAD signalling.Conclusion and ImplicationsIn bleomycin‐treated rats, early and persisting suppression of the BMP9/BMPR2/SMAD signalling pathway triggered severe loss of pulmonary arterial endothelium and subsequent pulmonary arterial vascular remodelling, contributing to the development of pulmonary hypertension. Therapeutic approaches reinforcing BMP9/BMPR2/SMAD signalling might be ideal strategies for this subtype of pulmonary hypertension.LINKED ARTICLESThis article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc
Prolonged unfolded protein reaction is involved in the induction of chronic myeloid leukemia cell death upon oprozomib treatment
Authors: Wang Fang , Wang Xin , Li Na , Liu Juan , Zhang Lin , Hui Lingyun , Feng Ai , Wang Zhonglin , Wang Yawen 
Published: October 2020

AbstractTo select the most efficient chemical to induce apoptosis in leukemia cells, a multidrug screen was applied on bone marrow mononuclear cells from chronic myeloid leukemia (CML) patients. Oprozomib (Cpd 21) was chosen for the subsequent experiments. The isobaric tags for relative and absolute quantitation (iTRAQ) was then performed to identify the responsible pathway relative to apoptosis and the results showed that endoplasmic reticulum (ER) chaperones were upregulated. Apoptosis was attributed to a joint effect of calcium leakage andPERK and IRE1α phosphorylation. The PERK branch was responsible for the first wave of cell death that occurred within 24 hours. The later wave of apoptosis was mediated by IRE1α, which transmit apoptotic signals through the ASK‐JNK‐BIM axis. Release of Ca2+ from ER into cytosol resulted in activation of calpain, which, in turn, cleaved caspase‐12. Our data also explained the selective killing effects of oprozomib on CML cells, which relied on proteasome activity. The present study demonstrated that prolonged inhibition of proteasome to trigger unfolded protein response could be an alternative strategy for treating CML in light of tyrosine kinase inhibitors resistance.
Differential glycosylation of collagen modulates lung cancer stem cell subsets through β1 integrin‐mediated interactions
Authors: Gardelli Cecilia , Russo Laura , Cipolla Laura , Moro Massimo , Andriani Francesca , Rondinone Ornella , Nicotra Francesco , Sozzi Gabriella , Bertolini Giulia , Roz Luca 
Published: October 2020

AbstractIn lung cancer, CD133+ cells represent the subset of cancer stem cells (CSC) able to sustain tumor growth and metastatic dissemination. CSC function is tightly regulated by specialized niches composed of both stromal cells and extracellular matrix (ECM) proteins, mainly represented by collagen. The relevance of collagen glycosylation, a fundamental post‐translational modification controlling several biological processes, in regulating tumor cell phenotype remains, however, largely unexplored. To investigate the bioactive effects of differential ECM glycosylation on lung cancer cells, we prepared collagen films functionalized with glucose (Glc‐collagen) and galactose (Gal‐collagen) exploiting a neoglycosylation approach based on a reductive amination of maltose and lactose with the amino residues of collagen lysines. We demonstrate that culturing of tumor cells on collagen determines a glycosylation‐dependent positive selection of CSC and triggers their expansion/generation. The functional relevance of CD133+ CSC increase was validated in vivo, proving an augmented tumorigenic and metastatic potential. High expression of integrin β1 in its active form is associated with an increased proficiency of tumor cells to sense signaling from glycosylated matrices (glyco‐collagen) and to acquire stemness features. Accordingly, inhibition of integrin β1 in tumor cells prevents CSC enrichment, suggesting that binding of integrin β1 to Glc‐collagen subtends CSC expansion/generation. We provide evidence suggesting that collagen glycosylation could play an essential role in modulating the creation of a niche favorable for the generation and selection/survival of lung CSC. Interfering with this crosstalk may represent an innovative therapeutic strategy for lung cancer treatment.
Kinetic studies of galectin-10 release from eosinophils exposed to proliferating T cells
Authors: Lingblom C , Andersson K , Wennerås C 
Published: October 2020

Summary
Galectin-10 is involved in the T cell suppressive activity of regulatory T cells and eosinophils alike. We have identified a subpopulation of T cell suppressive eosinophils that express CD16 on the surface and contain more galectin-10 compared with conventional CD16-negative eosinophils. Our main goal was to determine how the intracellular protein galectin-10 is released from eosinophils when exposed to proliferating T cells and if such release could be inhibited. Confocal microscopy and imaging flow cytometry were used to study the release of galectin-10 from eosinophils incubated with polyclonally activated T cells. T cell proliferation was monitored by measurement of the incorporation of [3H]-thymidine. Initially, galectin-10-containing synapses formed between eosinophils and T cells. Subsequently, the plasma membrane of eosinophils began to disintegrate and cap-like accumulations of galectin-10 budded on the eosinophil cell surface. Lastly, eosinophil extracellular traps composed of nuclear DNA and galectin-10 were freed. It was solely the CD16-expressing suppressive eosinophils that formed synapses and eosinophil extracellular traps containing galectin-10. Dissolution of the extracellular traps by DNase I partly abrogated the T cell suppression exerted by eosinophils. Extracellular trap formation has mainly been associated with anti-bacterial defense, but we show a new putative function of these cellular formations, as mediators of T cell suppression by enabling the release of galectin-10 from eosinophils.
Longitudinal economic analysis of Bonebridge 601 versus percutaneous bone‐anchored hearing devices over a 5‐year follow‐up period
Authors: Amin Nikul , Soulby Andrew Jonathan , Borsetto Daniele , Pai Irumee 
Published: October 2020

AbstractObjectivesPercutaneous bone‐anchored hearing devices (pBAHDs) are the most commonly used bone conduction implants (BCI). Concerns surround the long‐term complications, notably skin‐related, in patients with percutaneous abutments. The active transcutaneous BCI Bonebridge system can help avoid some of these pitfalls but is often considered a second‐line option due to various factors including perceived increased overall costs.DesignLongitudinal economic analysis of Bonebridge BCI 601 versus pBAHD over a 5‐year follow‐up period.SettingA specialist hearing implant centre.ParticipantsAdult patients (≥16 years) with conductive hearing loss, mixed hearing loss or single‐sided deafness, who received a Bonebridge or pBAHD implant between 1/7/2013 and 1/12/2018 with a minimum 12‐month follow‐up.Main outcome measuresWe compared the mean costs per implanted patient for both implants at 1, 3 and 5 years postoperative time points. Clinical effectiveness was evaluated using objective and patient‐reported outcome measures.ResultsThe mean total cost per patient of Bonebridge was significantly higher than pBAHD at 1‐year post‐implantation (£8512 standard deviation [SD] £715 vs £5590 SD £1394, P < .001); however, by 5‐years post‐implantation this difference was no longer statistically significant (£12 453 SD £2159 vs £12 575 SD £3854, P > .05). The overall cost convergence was mainly accounted for by the increased long‐term complications, revision surgery rates and higher cost of the pBAHD external processor compared to Bonebridge.ConclusionsLong‐term costs of Bonebridge to healthcare providers are comparable to pBAHDs, whilst offering lower complication rates, comparable audiological benefit and patient satisfaction. Bonebridge should be considered as a first‐line BCI option in appropriate cases.
ZNF300 promotes chemoresistance and aggressive behaviour in non‐small‐cell lung cancer
Authors: Yu Shilong , Ao Zhi , Wu Yi , Song Liyuan , Zhang Peng , Li Xiaokang , Liu Min , Qian Pin , Zhang Ruijie , Li Xihua , Chen Yan , Wang Xuanbin , Wang Xianhui , Ruan Xuzhi , Qian Guisheng , Ji Fuyun 
Published: October 2020

AbstractObjectivesChemoresistance induced by cisplatin has become the major impediment to lung cancer chemotherapy. This study explored the potential chemoresistant genes and underlying mechanisms of chemoresistance in NSCLC.Materials and methodsGene expression profile was integrated with DNA methylation profile to screen the candidate chemoresistant genes. Bioinformatic analysis and immunohistochemistry were used to analyse the association of a candidate gene with the characteristics of NSCLC patients. Recombinant lentivirus vectors were utilized to overexpress or silence candidate gene. Microarrays and immunoblotting were applied to explore the downstream targets of candidate gene. Xenograft models were established to validate the findings in vitro.ResultsAn increased ZNF300 expression was detected in three chemoresistant cell lines of NSCLC, and the higher expression of ZNF300 was associated with poor OS of NSCLC patients. Cells with upregulated ZNF300 presented chemoresistance and enhanced aggressive growth compared to cells with downregulated ZNF300. ZNF300 inhibited MAPK/ERK pathways and activated CDK1 through inhibiting WEE1 and MYT1 and modulating MYC/AURKA/BORA/PLK1 axis. ICA and ATRA improved the anti‐tumour effect of cisplatin on chemoresistant cells by inducing differentiation.ConclusionsZNF300 promotes chemoresistance and aggressive behaviour of NSCLC through regulation of proliferation and differentiation by downregulating MAPK/ERK pathways and regulation of slow‐cycling phenotype via activating CDK1 by inhibiting WEE1/MYT1 and modulating MYC/AURKA/BORA/PLK1 axis. Cisplatin, combined with ATRA and ICA, might be beneficial in chemoresistant cases of NSCLC.
Intravascular ultrasound–guided selection for early noninvasive cardiac allograft vasculopathy screening in heart transplant recipients
Authors: Nelson Lærke Marie , Rossing Kasper , Ihlemann Nikolaj , Boesgaard Søren , Engstrøm Thomas , Gustafsson Finn 
Published: October 2020

AbstractBackgroundNoninvasive screening for cardiac allograft vasculopathy (CAV) instead of invasive coronary angiography (ICA) within the first 3 to 5 years after heart transplantation (HTx) is controversial. We evaluated a strategy of intravascular ultrasound (IVUS)–guided conversion to early noninvasive screening post‐HTx.MethodsA single‐center study of 103 consecutive HTx recipients from 2008 to 2018 undergoing ICA at 1 year post‐HTx. Of 88 patients with normal 1‐year ICA, sixty‐six patients underwent IVUS examination for risk stratification by maximal intimal thickness (MIT) into (i) low‐risk group (MIT < 0.5 mm) (n = 41, 62%) followed noninvasively versus (ii) high‐risk group (MIT ≥ 0.5 mm) (n = 25, 38%) followed with yearly ICA. Both groups underwent ICA at year 5 post‐HTx. We evaluated a combined endpoint of angiographic CAV and death at 5‐year follow‐up post‐HTx.ResultsMedian (IQR) age was 51 (33–60) years, and 62% were male. Follow‐up was 1443 (1125–1456) days. Survival free from angiographic CAV (Kaplan‐Meier) differed significantly between groups (log‐rank p < .0001). A subgroup of 27 patients completed ICA at year 5, and the proportion of angiographic CAV was significantly lower in low‐risk patients (p < .0001).ConclusionIVUS‐guided selection for early noninvasive CAV screening appears to be safe and holds promise as a novel strategy for early risk stratification and CAV surveillance post‐HTx.
Use as directed: do standard drink labels on alcohol containers help consumers drink (ir)responsibly? Real‐world evidence from a quasi‐experimental study in Yukon, Canada
Authors: Schoueri‐Mychasiw Nour , Weerasinghe Ashini , Stockwell Tim , Vallance Kate , Hammond David , Greenfield Thomas K. , McGavock Jonathan , Hobin Erin 
Published: October 2020

AbstractIntroduction and AimsThis paper examines the impact of an alcohol labelling intervention on recall of and support for standard drink (SD) labels, estimating the number of SDs in alcohol containers, and intended and unintended use of SD labels.Design and MethodsA quasi‐experimental study was conducted in Canada where labels with a cancer warning, national drinking guidelines and SD information were applied to alcohol containers in the single liquor store in the intervention site, while usual labelling continued in the two liquor stores in the comparison site. Three waves of surveys were conducted in both sites before and at two time‐points after the intervention with 2049 cohort participants. Generalised estimating equations were applied to estimate changes in all outcomes.ResultsParticipants in the intervention relative to the comparison site had greater odds of recalling [adjusted odds ratio (AOR) 5.69, 95% confidence interval (CI) 3.02, 10.71] and supporting SD labels (AOR 1.49, 95% CI 1.04, 2.12) and lower odds of reporting using SD labels to purchase high strength, low‐cost alcohol (AOR 0.65, 95% CI 0.45, 0.93). Exposure to the labels had negligible effects on accurately estimating the number of SDs (AOR 1.06, 95% CI 0.59, 1.93) and using SD labels to drink within guidelines (AOR 1.04, 95% CI 0.75, 1.46).Discussion and ConclusionsEvidence‐informed labels increased support for and decreased unintended use of SD labels. Such labels can improve accuracy in estimating the number of SDs in alcohol containers and adherence to drinking guidelines.
Clockwise and counterclockwise hysteresis characterize state changes in the same aquatic ecosystem
Authors: Northrop Amanda C. , Avalone Vanessa , Ellison Aaron M. , Ballif Bryan A. , Gotelli Nicholas J. 
Published: October 2020

AbstractIncremental increases in a driver variable, such as nutrients or detritus, can trigger abrupt shifts in aquatic ecosystems that may exhibit hysteretic dynamics and a slow return to the initial state. A model system for understanding these dynamics is the microbial assemblage that inhabits the cup‐shaped leaves of the pitcher plant Sarracenia purpurea. With enrichment of organic matter, this system flips within three days from an oxygen‐rich state to an oxygen‐poor state. In a replicated greenhouse experiment, we enriched pitcher‐plant leaves at different rates with bovine serum albumin (BSA), a molecular substitute for detritus. Changes in dissolved oxygen (DO) and undigested BSA concentration were monitored during enrichment and recovery phases. With increasing enrichment rates, the dynamics ranged from clockwise hysteresis (low), to environmental tracking (medium), to novel counter‐clockwise hysteresis (high). These experiments demonstrate that detrital enrichment rate can modulate a diversity of hysteretic responses within a single aquatic ecosystem, and suggest different management strategies may be needed to mitigate the effects of high vs. low rates of detrital enrichment.
Early transcriptional changes after UVB treatment in atopic dermatitis include inverse regulation of IL‐36γ and IL‐37
Authors: Lossius Astrid H. , Berents Teresa L. , Sætre Frank , Nilsen Hogne R , Bradley Maria , Asad Samina , Haraldsen Guttorm , Sundnes Olav , Holm Jan‐Øivind 
Published: October 2020

AbstractPhototherapy with narrow‐band Ultraviolet B (nb‐UVB) is a major therapeutic option in atopic dermatitis (AD), yet knowledge of the early molecular responses to this treatment is lacking. The objective of this study was to map the early transcriptional changes in AD skin in response to nb‐UVB treatment. Adult patients (n = 16) with AD were included in the study and scored with validated scoring tools. AD skin was irradiated with local nb‐UVB on day 0, 2 and 4. Skin biopsies were taken before and after treatment (day 0 and 7) and analysed for genome‐wide modulation of transcription. When examining the early response after three local UVB treatments, gene expression analysis revealed 77 significantly modulated transcripts (30 down‐ and 47 upregulated). Among them were transcripts related to the inflammatory response, melanin synthesis, keratinization and epidermal structure. Interestingly, the pro‐inflammatory cytokine IL‐36γ was reduced after treatment, while the anti‐inflammatory cytokine IL‐37 increased after treatment with nb‐UVB. There was also a modulation of several other mediators involved in inflammation, among them defensins and S100 proteins. This is the first study of early transcriptomic changes in AD skin in response to nb‐UVB. We reveal robust modulation of a small group of inflammatory and anti‐inflammatory targets, including the IL‐1 family members IL36γ and IL‐37, which is evident before any detectable changes in skin morphology or immune cell infiltrates. These findings provide important clues to the molecular mechanisms behind the treatment response and shed light on new potential treatment targets.
Renal disease associated with myeloproliferative neoplasms and myelodysplastic syndrome/myeloproliferative neoplasms
Authors: Büttner‐Herold Maike , Sticht Carsten , Wiech Thorsten , Porubsky Stefan 
Published: October 2020

AimsRenal changes in patients with myeloproliferative neoplasms (MPNs) or myelodysplastic syndrome (MDS)/MPNs have been addressed by few, respectively no, reports. The aim of this study was to focus on a systematic evaluation of renal biopsies in patients with MPNs or MDS/MPNs.Methods and resultsThe cohort comprised 29 patients (23 men) aged 67 ± 11 years (mean ± standard deviation), diagnosed with chronic myeloid leukaemia (n = 5), polycythaemia vera (n = 9), primary myelofibrosis (n = 5), essential thrombocythaemia (n = 2), or chronic myelomonocytic leukaemia (n = 4), as well as MPNs or MDS/MPNs not otherwise specified (n = 4). Patients manifested with proteinuria (93%), partially in the nephrotic range (46%), haematuria (72%), and impaired kidney function (93%). The most prominent histological findings included double‐contoured glomerular basement membranes (71%), acute endothelial damage (68%), intracapillary platelet aggregation (62%), mesangiolysis (21%), thrombotic microangiopathy (24%), segmental glomerulosclerosis (66%), mesangial hypercellularity and sclerosis, extramedullary haematopoiesis (17%), and also IgA nephropathy (21%) and glomerulonephritis (GN) with features of infection‐related GN (21%). MPN and MDS/MPN patients showed significantly more chronic changes than age‐matched and sex‐matched controls, including global and segmental glomerulosclerosis, mesangial sclerosis, and hypercellularity, whereas the extent of arteriosclerosis was comparable.ConclusionsMPN and MDS/MPN patients show glomerular scarring that exceeds age‐related phenomena. Ongoing endothelial damage, growth factors released by platelets and deposition of immune complexes are probably the causative mechanisms. Early recognition of renal failure heralded by proteinuria and haematuria, and consequent control of risk factors for kidney failure, should be recommended for MPN and MDS/MPN patients.
MicroRNAs in urine as diagnostic biomarkers for multiple myeloma
Authors: Li Jia , Wang Chengbin , Meng Qian , Hu Zhiying , Hu Mei , Zhang Man 
Published: October 2020

AbstractIntroductionMultiple myeloma (MM) is a hematological malignancy. It is of great clinical significance to screen microRNAs (miRNAs) in urine as noninvasive diagnostic biomarkers for MM.MethodsUrinary miRNAs in MM were performed by Agilent Bioanalyzer 2100 and verified by quantitative real‐time PCR (qRT‐PCR). Receiver operator characteristic (ROC) was used to evaluate the diagnostic value of abnormal miRNAs for MM. Progression‐free survival (PFS) of MM was calculated by Kaplan‐Meier.ResultsIn microarray analysis, twelve down‐regulated miRNAs dysregulated in MM. The expression levels of miR‐134‐5p, miR‐6500‐5p, miR‐548q, and miR‐548y were validated. These miRNAs were significantly lower in MM (P < .05), but there was no significant difference between newly diagnosed, relapse, and remission group of MM (P> .05). ROC curve analysis showed that the sensitivity of miR‐134‐5p, miR‐6500‐5p, miR‐548q, and miR‐548y to MM was 91.7%, 100%, 100%, and 91.7%, and the specificity was 66.7%, 75.0%, 75.0%, and 100%, respectively. The four miRNAs were negatively correlated with the total urinary light chain (r = −0.427 P = .030, r = −0.461 P = .018, r = −0.469 P = .016, r = −0.493 P = .011). In addition, miR‐134‐5p, miR‐6500‐5p, and miR‐548q were positively correlated with serum ALB (r = 0.518 P = .006, r = 0.400 P = .039,r = 0.492 P = .009). The expression level of miRNAs had no significant influence on PFS in MM patients (P> .05).ConclusionThe results show that miR‐134‐5p, miR‐6500‐5p, miR‐548q, and miR‐548y are potential noninvasive diagnostic biomarkers for MM.
Effectiveness of healthy eating interventions among children: A quantitative systematic review
Authors: Shorey Shefaly , Chan Valerie 
Published: October 2020

AbstractAimsThis review aimed to evaluate the effectiveness of healthy eating interventions among normal‐weight children.DesignA systematic review of randomized controlled trials.Data sourcesSeven databases were searched from the inception of each database until September 2019.Review MethodsA systematic review of quantitative studies was reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines and the PRISMA extension for reporting a synthesis without a meta‐analysis.ResultsFifteen studies were included in this review. A meta‐analysis could not be conducted because of the observed heterogeneity across studies. There were mixed effects of the included interventions on healthy eating habits, ranging from effective to not effective. Only a few studies found behavioural determinants effective in enhancing healthy eating.ConclusionBecause of the observed heterogeneity and varied outcome variables, a meta‐analysis could not be conducted, and the overall effectiveness of the included interventions could not be verified. Interventions that were theory based, parent focused, and delivered through the multimodal interactive approach were found to be effective in enhancing healthy eating habits among children. More studies involving peers that are institution based need to be conducted.