bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro PUVA treatment triggers calreticulin exposition and HMGB1 release by dying T lymphocytes in GVHD: New insights in extracorporeal photopheresis
Authors: Coppard Céline , Hannani Dalil , Humbert Marion , Gauthier Virginie , Plumas Joel , Merlin Etienne , Gabert Françoise , Chaperot Laurence 
Published: March 2019

AbstractBackgroundExtracorporeal photopheresis (ECP) is an effective therapy for graft vs host disease (GVHD), based on infusion of UVA‐irradiated and 8 methoxy‐psoralen (PUVA)‐treated leukocytes. Reinfusion of these apoptosing cells affects the functionality of pathogenic T cells through poorly understood immunomodulatory mechanisms. Apoptosis is usually a silent, tolerance‐associated process, but can also be immunogenic, depending on death‐inducers and environmental context.MethodsTo understand ECP mechanisms of action, human alloreactive T cells generated in an in vitro model mimicking GVHD were used, as well as primary cells from GVHD patients. Cells were submitted to PUVA treatment and their phenotype and immunogenicity were analyzed, using cell culture and flow cytometry.ResultsIn vitro PUVA treatment induced the expression of several damage‐associated molecular patterns (DAMPs) by dying T cells (calreticulin, high‐mobility group box‐1, and to a lesser extent heat shock proteins 70 and 90), especially upon T cell activation, leading to their phagocytosis by macrophages and dendritic cells (DCs). Allogeneic DCs preincubated with PUVA treated T cells induced comparable naive T cell proliferation and polarization as control allogeneic DC.ConclusionAltogether, in our experimental settings, in vitro PUVA‐treatment induces a partially immunogenic phenotype allowing phagocytosis of apoptotic cells by macrophages and DC, however not sufficient to induce dendritic cell maturation and T cell activation. These data refine current models of ECP‐mediated immune modulation and emphasize the need to further analyze PUVA‐treated cell interactions with immune cells.
Circulating microRNA‐133, microRNA‐17 and microRNA‐25 in serum and its potential diagnostic value in gastric cancer
Authors: ZiaSarabi Parisa , Sorayayi Saba , Hesari AmirReza , Ghasemi Faezeh 
Published: March 2019

AbstractGastric cancer is one of the most common malignancies in the world and is considered as the most lethal gastrointestinal cancer. microRNAs (miRNAs) can be very important in detecting a disease at an early stage. The aim of this study was to investigate the microRNA‐17 (miR‐17), miR‐25, and miR‐133b in the serum of gastric cancer subjects. Serum samples were obtained from 120 gastric cancers and 102 healthy subjects. We evaluated expression levels of miR‐17, miR‐25 and miR‐133b by quantitative real‐time polymerase chain reaction. Our results showed that in the patients with gastric cancer, the expression level of miR‐17 and miR‐25 were significantly increased compared with the control group (P < 0.5), while the expression level of miR‐133b was significantly decreased in patient groups compared with control cases (P < 0.5). It seems that expression of miRNAs in Iranian patients with gastric cancer is similar to other patients in other populations. These findings suggested that miR‐17, miR‐25 and miR‐133b could be introduced as potential diagnostic candidates for the detection in gastric cancer patients in the early stage.
Reduning injection ameliorates paraquat‐induced acute lung injury by regulating AMPK/MAPK/NF‐κB signaling
Authors: Jiang Cuihua , Zhong Rongling , Zhang Jian , Wang Xiangxiang , Ding Gang , Xiao Wei , Ma Shiping 
Published: March 2019

AbstractReduning injection (RDN), a patented Chinese medicine, is broadly used for common cold and lung infection in clinic, but the mechanism underlying its effects on inflammation‐related pulmonary injury remains unclear. Paraquat (PQ, bolus 15 mg/kg dose, ip) was administered for acute lung injury induction in mice, which were orally administered dexamethasone (2 mg/kg) or RDN (50 and 100 mg/kg/day) for 5 days. After treatment, plasma and lung tissue samples from the euthanized animals were obtained and analyzed by histological, biochemical and immunoblot assays. Histological observation demonstrated RDN alleviated PQ‐induced lung damage. Meanwhile, RDN suppressed myeloperoxidase (MPO) activity, reduced the wet/dry (W/D) ratio and decreased the amounts of total leukocytes and neutrophils. Treatment also markedly decreased the amounts of malondialdehyde, MPO, and inflammatory cytokines while increasing superoxide dismutase activity in comparison with the PQ group. In immunoblot, RDN blocked the phosphorylation levels of adenosine 5′‐monophosphate (AMP)‐activated protein kinase (AMPK), JNK, ERK, p38, inhibitor of nuclear factor κB kinase and nuclear factor‐κB (NF‐κB) in lung tissue specimens in PQ‐challenged animals, which was further verified in vitro. The above data indicated protective effects for RDN in PQ‐induced lung damage, possibly through inhibition of the AMPK/MAPK/NF‐κB pathway.
In utero transplantation of neural stem cells ameliorates maternal inflammation‐induced prenatal white matter injury
Authors: Borhani‐Haghighi Maryam , Mohamadi Yousef , Kashani Iraj Ragerdi 
Published: March 2019

AbstractPrenatal white matter injury is a serious problem due to maternal inflammation leading to postnatal disabilities. In this study, we used the periventricular leukomalacia (PVL) model as a common prenatal white matter injury by maternal administration of lipopolysaccharide (LPS). Neural stem cells (NSCs) have shown therapeutic ability in neurological disorders through a different mechanism such as immunomodulation. Here, we studied the preventive potential of NSCs following in utero transplantation into the embryonic lateral ventricle in an LPS‐induced white matter injury model. Pregnant animals were divided into three groups and received phosphate buffered saline, LPS, or LPS + NSCs. The brains of offspring were obtained and evaluated by real‐time polymerase chain reaction (PCR), immunohistochemy, enzyme‐linked immunosorbent assay (ELISA), terminal deoxynucleotidyl transferase‐mediated biotinylated‐dUTP nick‐end labeling (TUNEL), and caspase‐3 activity assay. The LPS‐induced maternal inflammation degenerated the myelin sheath in the offspring periventricular region which was associated with an increased microglial number, oligodendrocytes degeneration, proinflammatory cytokine secretion, and cell apoptosis. The transplanted NSCs homed into the brain and ameliorated the evaluated parameters. The expression of proinflammatory cytokines interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor‐α (TNF‐α), cell apoptosis and caspase‐3 activity were inhibited by NSCs. In addition, Olig2 and myelin basic protein immunohistochemy staining showed that prenatal NSCs transplantation augmented the myelination in the periventricular white matter of offspring. In conclusion, we think that prenatal therapeutic strategies, such as in utero NSCs transplantation, may prevent prenatal white matter injury after birth.
Association between rs4938723 polymorphism and the risk of primary open‐angle glaucoma (POAG) in a Chinese population
Authors: Zhang Jian , Wang Li 
Published: March 2019

AbstractIn this study, we aimed to investigate the association between rs4938723 single‐nucleotide polymorphism (SNP) and the risk of primary open‐angle glaucoma (POAG) in a Chinese population to clarify the molecular mechanism underlying the pathogenesis of POAG. Taqman assays and statistical analyses were utilized to analysis the associations between rs4938723 SNP/rs1042522 SNP and the risk of POAG. Luciferase assays, in‐silicon analyses, real‐time PCR, Western Blot, 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide (MTT) assay, and flow cytometry were conducted to establish a molecular pathway underlying the protective effect of rs4938723 T > C SNP against the risk of POAG. The maximum intraocular pressure (IOP) was evidently higher in the case group compared with that in the control group. The risk of POAG was evidently decreased among carriers of the CT/CC genotypes under a dominant model. In addition, the risk of POAG was also significantly decreased in the carriers of the CC genotype. In contrary, no significant association was found between the risk of POAG and the rs1042522 SNP in
TP53 gene. In addition, rs4938723 (especially rs4938723 T > C) SNP could elevate the transcription efficiency of miR‐34b promoter and the suppression of TP53, a virtual target of miR‐34b. Therefore, the presence of anti‐miR‐34b suppressed cell proliferation and promoted cell apoptosis, thus establishing a molecular mechanism underlying the protective effect of rs4938723 polymorphism T > C against the risk of POAG. Rs4938723 polymorphism T > C could reduce the incidence of POAG by downregulating TP53 expression, thus leading to suppressed cell apoptosis and enhanced cell proliferation.
PIAS genes as disease markers in bipolar disorder
Authors: Sayad Arezou , Taheri Mohammad , Azari Iman , Oskoei Vahid Kholghi , Ghafouri‐Fard Soudeh 
Published: March 2019

AbstractThe protein inhibitors of activated STAT (PIAS) are involved in regulation of many transcription factors and signaling pathways that contribute to the pathogenesis of bipolar disease (BD). In the current study, we evaluated the expression of four PIAS genes (PIAS1‐4) in peripheral blood of BD patients and healthy subjects to explore their contribution in the pathogenesis of BD and their suitability as peripheral biomarkers for this disorder. All PIAS genes were significantly upregulated in total BD patients compared with total controls. The sex‐based analysis confirmed upregulation of PIAS1‐4 genes in male BD patients compared with male controls (P < 0.001). However, PIAS1 was significantly downregulated in female patients compared with female controls (P = 0.02). Expression levels of other PIAS genes were not significantly different between female patients and female controls. There were no significant correlations between expression levels of PIAS genes and any of the clinical data of study participants after adjustment of the effects of the sex. On the basis of the area under the curve (AUC) values in receiver operating characteristic curves, PIAS4 had the best performance in the differentiation of disease status between study participants (AUC = 0.81). PIAS3 and PIAS4 genes had the best sensitivity and specificity values, respectively. Combination of expression levels of four genes resulted in the improvement of diagnostic power (AUC = 0.82). The current data implies the role of PIAS genes in the pathogenesis of BD and denotes their suitability as peripheral markers for this disorder.
Comprehensive analyses of DNA methylation and gene expression profiles of Kawasaki disease
Authors: Chang Danqi , Qian Cheng , Li Hang , Feng Hong 
Published: March 2019

AbstractObjectiveKawasaki disease (KD) is a childhood febrile vasculitis with unknown etiology. Epigenetic regulation in the gene expression dynamics has become increasingly important in KD. Thus, we performed an integrated analysis of DNA methylation and gene expression data to identify novel molecular mechanisms and key functional genes in KD.MethodsDNA methylation (GSE84624) and gene expression (GSE68004) datasets were downloaded from Gene Expression Omnibus. Methylated‐differentially expressed genes (mDEGs) were documented as the overlapping genes between the differentially methylated genes (DMGs) in GSE84624 and differentially expressed genes (DEGs) in GSE68004. Functional enrichment analyses of the mDEGs were conducted using DAVID database. Protein‐protein interaction (PPI) network was then constructed to obtain the hub genes involved in KD using STRING database.ResultsA total of 1389 DMGs and 1362 DEGs were screened out between KD and control samples. Overlapping of them resulted in four hypermethylated/downregulated and 187 hypomethylated/upregulated genes. These mDEGs were mainly enriched in inflammation response, innate immune response, and blood coagulation, and signaling pathways such as platelet activation, osteoclast differentiation, and chemokine signaling pathway. PPI network analyses identified MAPK14 and PHLPP1 as the hub genes involved in KD, which could distinguish KD from other common pediatric febrile diseases. In addition, the methylation and expression levels of MAPK14 and PHLPP1 were validated in other independent datasets.ConclusionThis study provides an integrated view of interactions among DNA methylation and gene expression in patients with KD. MAPK14 and PHLPP1 are the key genes influenced by methylation and may serve as candidate biomarkers for KD.
Evaluation of the BioPlex 2200 syphilis total screen (IgG/IgM) with reflex to an automated rapid plasma reagin test
Authors: Rourk Angela R. , Litwin Christine M. 
Published: March 2019

AbstractBackgroundWe evaluated the recently FDA cleared BioPlex 2200 Syphilis Total Screen and automated rapid plasma reagin (RPR) assay for the detection of total (IgG/IgM) treponemal and non‐treponemal antibodies in the reverse syphilis algorithm.MethodsProspectively submitted samples (n = 885) were assayed by both the IgG/IgM BioPlex Syphilis Screen and the original IgG BioPlex Syphilis Screen. The IgG screen reactive samples were reflexed to traditional RPR, and IgG/IgM screen reactive samples were reflexed to the automated RPR. Nonreactive RPR samples were tested by the Treponemal Pallidum Particle Agglutination test (TP‐PA). Additional samples were collected (n = 404 total samples) to directly compare the automated and traditional RPR assays with each other.ResultsThe sensitivity and specificity of the IgG/IgM screen with automated RPR was 95.6% (95% confidence interval [CI] 87.0‐99.1) and 99.6% (CI 99.2‐99.8) while the sensitivity and specificity of the BioPlex IgG screen with traditional RPR was 97.8% (CI 89.1‐99.9) and 99.3% (CI 98.8‐99.4). The sensitivity and specificity of the BioPlex RPR compared with traditional RPR was 95.8% (CI 93.9‐97.0) and 94.1% (CI 89.4‐91.1) and 95.3% (CI 92.6‐97.1). The mean of the titer differences between the BioPlex RPR and the traditional RPR was 1.0 ± 0.9 SD titers.ConclusionThe addition of the detection of treponemal IgM antibodies to the IgG/IgM screen did not significantly affect the sensitivity and specificity compared to the original IgG screen. However, the addition of the comparable BioPlex RPR assay to the instrumentation significantly reduces the overall labor of syphilis screening and confirmation.
Genetic counseling for consumer‐driven whole exome and whole genome sequencing: A commentary on early experiences
Authors: Schmidt Johanna L. , Maas Roxanne , Altmeyer Sharon Reid 
Published: March 2019

AbstractCounseling after consumer‐driven whole exome sequencing (WES) and whole genome sequencing (WGS) presents challenges for genetic counselors as availability of this testing increases. There are no standard practice guidelines and limited resources for genetic counselors in this area, but consumer demand for counseling and data interpretation exists and is likely to grow along with testing opportunities. In this paper, we comment upon our experiences as three independent, private practice genetic counselors who have provided counseling services for clients with WES/WGS reports and data. In our counseling experience, we have encountered three main types of client motivation for seeking testing and counseling: generally healthy individuals who are curious to learn more about their genomic data, individuals with family histories of various conditions, and/or who want to better understand specific disease risks, and individuals who are ill, undiagnosed and searching for an understanding of their ailments. Research is needed to better understand client motivations for undergoing testing and counseling, as well outcomes of counseling sessions. In addition to improvements in variant identification, classification and bioinformatics, there is a need for practice guidelines, counseling resources, service delivery models, and efforts to increase awareness and access to genetic counseling services.
Usefulness of ultrasonographic evaluation of stool and/or gas distribution for the treatment strategy of chronic constipation
Authors: Manabe Noriaki , Kamada Tomoari , Kusunoki Hiroaki , Hata Jiro , Haruma Ken 
Published: March 2019

Background and AimThis study aimed to evaluate the capability of ultrasonography to predict favorable outcomes of various medical therapies in patients with chronic constipation.MethodsWe enrolled 223 patients with chronic constipation (75 men, 148 women; mean age 62.9 ± 3.4 years). Transverse diameters of four segments of the colon (ascending [A], transverse [T], descending [D], sigmoid [S]), and the rectum [R]) were measured. The patients' stool and/or gas distribution was evaluated using the constipation index (CI) ([A + T + D + S + R]/5) and the left/right distribution ratio ([D + S]/[A + T]) according to our previous study. Patients were first treated with fiber‐ or osmosis‐based laxatives for 2 weeks. When constipation was not alleviated, stimulant‐based laxatives were added, and the patients were followed for another 2 weeks.ResultsBased on their clinical courses, patients were divided into four groups: nonresponders (group A) or responders (group B) to fiber‐ or osmosis‐based laxatives; nonresponders to any medical therapy (group C); and responders to stimulant‐based laxatives (group D). The CI was significantly higher in group A than group B (P < 0.05), with the receiver operating characteristic (ROC) curve analysis showing a CI cut‐off of 21.2 for predicting favorable outcomes of either fiber‐ or osmosis‐based laxatives (P < 0.05). Left/right distribution ratio was significantly lower in group C than group D (P < 0.05), and the ROC curve analysis showed a left/right cut‐off of 0.5 for predicting responders to stimulant‐based laxatives (P < 0.05).ConclusionThese findings could help physicians predict favorable outcomes with laxatives without side effects for this patient population.
Patterns of alcohol consumption and nutrition intake in patients with alcoholic liver disease and alcoholic pancreatitis in North Indian men
Authors: Singh Karam R , Muktesh Gaurav , Gunjan Deepak , Kochhar Rakesh , Singh Virendra , Das Ashim , Siddappa Pradeep , Singh Kartar 
Published: March 2019

Background and AimChronic alcoholism and nutrition play an important role in liver and pancreatic diseases. To compare drinking habits and nutritional data in patients with alcoholic liver disease (ALD) and alcoholic pancreatitis (ALP).MethodsClinical, anthropometric, dietary intake, laboratory, and imaging data were recorded in consecutive patients of ALD and ALP.ResultsIn 150 patients of ALP (n = 76) and ALD (n = 74), the age of starting alcohol consumption (19.03 ± 3.78 vs 18.0 ± 2.59 years) and the mean amount of alcohol consumed per day (165.63 ± 87.99 vs 185.50 ± 113.54 g; P = 0.230) were similar. Patients with ALD consumed alcohol on a daily basis more frequently (90.5 vs 72.3%; P = 0.003) and had a longer duration of alcohol intake (21.6 + 0.2 vs 14.5 + 6.9 years; P < 0.0001) than patients in the ALP group. Binge drinking was more common in patients with ALP compared to patients with ALD (60.5 vs 20.3%); P < 0.0001). Patients with ALP had a lower body mass index (19.9 ± 3.49 vs 22.64 ± 4.88 kg/m2; P = 0.001) and more frequent decrease in mid arm circumference (57.9 vs 44.6%; P = 0.042) and triceps skin fold thickness (67.1 vs 52.7%; P = 0.072) compared to patients with ALD.ConclusionThere was no difference in the age of starting alcohol consumption and mean amount of alcohol consumption per day between the groups. Patients with ALD were more likely to be daily drinkers with a longer duration of alcohol intake. However, binge drinking and malnourishment was more common in the ALP group.
MDM2 and its functional polymorphism SNP309 contribute to the development of esophageal carcinoma
Authors: Xiao Fan‐kai , Guo Sen , Yang Fan , Zhao Luo‐sha , Wang Li‐dong 
Published: March 2019

AbstractBackgroundOverexpression of the murine double minute 2 (MDM2) has been explored in many tumors with high proliferation and anti‐apoptosis ability. However, the role of MDM2 and its functional single nucleotide polymorphism (SNP) rs2279744 (also known as SNP309) in esophageal squamous cell carcinoma (ESCC) remains unclear.MethodsWe performed a genotype study of blood samples in 360 ESCC patients and 360 healthy control individuals to determine the risk of various rs2279744 in ESCC. To further evaluate the role of rs2279744 in regulating MDM2 expression, we performed an allele‐specific reporter assay and investigated whether the SNP‐containing sequences functioned as an active enhancer. To examine the functional role of MDM2 on esophageal cancer cell lines, we carried out an MTS assay and flow cytometry analysis.ResultsFrom the genotyping study, we found that GG genotype of SNP309 significantly increased the risk of ESCC in an additive model [odds ratio (OR) = 2.55, 95% confidence interval (CI) = 1.66–3.89, p = 1.50 × 10–5) and in a recessive model (OR = 2.44, 95% CI = 1.69–3.51, p = 1.60 × 10–8). Furthermore, the G allele was significantly associated with a higher risk of ESCC (OR = 1.56, 95% CI = 1.26–1.92, p = 2.81 × 10–5). In multivariate logistic regression analysis, the GG genotype had increased the occurrence of ESCC by 2.39‐fold (95% CI = 1.48–3.8). Compared to the T allele, the variant G allele had significantly higher luciferase activity on the promoter of MDM2 in both cell lines. By transfecting the gene to ESCC lines, we showed that overexpression of MDM2 significantly promote cell proliferation and anti‐apoptosis.ConclusionsThe MDM2 promoter SNP309 is a risk factor for esophageal cancer. MDM2 promotes the proliferation and anti‐apoptosis of ESCC.
Measuring tissue sodium concentration: Cross‐vendor repeatability and reproducibility of 23Na‐MRI across two sites
Authors: Riemer Frank , McHugh Damien , Zaccagna Fulvio , Lewis Daniel , McLean Mary A. , Graves Martin J. , Gilbert Fiona J. , Parker Geoff J.M. , Gallagher Ferdia A. 
Published: March 2019

BackgroundSodium MRI (23Na‐MRI)‐derived biomarkers such as total sodium concentration (TSC) have the potential to provide information on tumor cellularity and the changes in tumor microstructure that occur following therapy.PurposeTo evaluate the repeatability and reproducibility of TSC measurements in the brains of healthy volunteers, providing evidence for the technical validation of 23Na‐MRI‐derived biomarkers.Study TypeProspective multicenter study.SubjectsEleven volunteers (32 ± 6 years; eight males, three females) were scanned twice at each of two sites.Field Strength/SequenceComparable 3D‐cones 23Na‐MRI ultrashort echo time acquisitions at 3T.AssessmentTSC values, quantified from calibration phantoms placed in the field of view, were obtained from white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF), based on automated segmentation of coregistered 1H T1‐weighted images and hand‐drawn regions of interest by two readers.Statistical TestsCoefficients of variation (CoVs) from mean TSC values were used to assess intrasite repeatability and intersite reproducibility.ResultsMean GM TSC concentrations (52.1 ± 7.1 mM) were ∼20% higher than for WM (41.8 ± 6.7 mM). Measurements were highly repeatable at both sites with mean scan–rescan CoVs between volunteers and regions of 2% and 4%, respectively. Mean intersite reproducibility CoVs were 3%, 3%, and 6% for WM, GM, and CSF, respectively.Data ConclusionThese results demonstrate technical validation of sodium MRI‐derived biomarkers in healthy volunteers. We also show that comparable 23Na imaging of the brain can be implemented across different sites and scanners with excellent repeatability and reproducibility.Level of Evidence: 1Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2019;50:1278–1284.