bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induced pluripotent stem cell‐derived extracellular vesicles: A novel approach for cell‐free regenerative medicine
Authors: Taheri Behnaz , Soleimani Masoud , Fekri Aval Sedigheh , Esmaeili Elaheh , Bazi Zahra , Zarghami Nosratollah 
Published: November 2018

AbstractIn recent years, induced pluripotent stem cells (iPSCs) have been considered as a promising approach in the field of regenerative medicine. iPSCs can be generated from patients’ somatic cells and possess the potential to differentiate, under proper conditions, into any cell type. However, the clinical application of iPS cells is restricted because of their tumorigenic potential. Recent studies have indicated that stem cells exert their therapeutic benefit via a paracrine mechanism, and extracellular vesicles have been demonstrated that play a critical role in this paracrine mechanism. Due to lower immunogenicity, easier management, and presenting no risk of tumor formation, in recent years, researchers turned attention to exosomes as potential alternatives to whole‐cell therapy. Application of exosomes derived from iPSCs and their derived precursor provides a promising approach for personalized regenerative medicine. This study reviews the physiological functions of extracellular vesicles and discusses their potential therapeutic benefit in regenerative medicine.
Association between miRNAs expression and signaling pathways of oxidative stress in diabetic retinopathy
Authors: Satari Mahbobeh , Aghadavod Esmat , Mobini Moein , Asemi Zatollah 
Published: November 2018

AbstractDiabetic retinopathy (DR) is a major cause of vision reduction in diabetic patients. Hyperglycemia is a known instigator for the development of DR, even though the role of oxidative stress pathways in the pathogenesis of DR is established. The studies indicate that microRNAs (miRNAs) are significant to the etiology of DR; changes in miRNAs expression levels may be associated with onset and progression of DR. In addition, miRNAs have emerged as a useful disease marker due to their availability and stability in detecting the severity of DR. The relationship between miRNAs expression levels and oxidative stress pathways has been investigated in several studies. The aim of this study is the examination of function and expression levels of target miRNAs in oxidative stress pathway and pathogenesis of diabetic retinopathy.
Poly (3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) improved osteogenic differentiation of the human induced pluripotent stem cells while considered as an artificial extracellular matrix
Authors: Hosseini Fatemeh Sadat , Soleimanifar Fatemeh , Aidun Amir , Enderami Seyedeh Elnaz , Saburi Ehsan , Marzouni Hadi Zare , Khani Mohammad‐Mehdi , Khojasteh Arash , Ardeshirylajimi Abdolreza 
Published: November 2018

AbstractCocell polymers can be the best implants for replacing bone defects in patients. The pluripotent stem cells produced from the patient and the nanofibrous polymeric scaffold that can be completely degraded in the body and its produced monomers could be also usable are the best options for this implant. In this study, electrospun poly (3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV) nanofibers were fabricated and characterized and then osteogenic differentiation of the human‐induced pluripotent stem cells (iPSCs) was investigated while cultured on PHBV scaffold. MTT results showed that cultured iPSCs on PHBV proliferation were increased compared to those cultured on tissue culture polystyrene (TCPS) as the control. Alkaline phosphatase (ALP) activity and calcium content were also significantly increased in iPSCs cultured on PHBV compared to the cultured on TCPS under osteogenic medium. Gene expression evaluation demonstrated that Runx2, collagen type I, ALP, osteonectin, and osteocalcin were upregulated in iPSCs cultured on PHBV scaffold in comparison with those cultured on TCPS for 2 weeks. Western blot analysis have shown that osteocalcin and osteopontin expression as two major osteogenic markers were increased in iPSCs cultured on PHBV scaffold. According to the results, nanofiber‐based PHBV has a promising potential to increase osteogenic differentiation of the stem cells and iPSCs‐PHBV as a cell‐co‐polymer construct demonstrated that has a great efficiency for use as a bone tissue engineered bioimplant.
Long noncoding RNA NEAT1 promotes the growth of human retinoblastoma cells via regulation of miR‐204/CXCR4 axis
Authors: Zhong Wei , Yang Jingpu , Li Miyang , Li Lin , Li Aipeng 
Published: November 2018

AbstractRetinoblastoma (RB) is an aggressive eye cancer of infancy and childhood with high mortality. Studies have shown that long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) is closely related to the progression of multiple cancers. However, its role in RB remains unknown. This study aimed to investigate the role and underlying mechanism of NEAT1 in RB. We first detected the expression of NEAT1 in human RB tissues and cell lines. The effects of NEAT1 on the proliferation, migration, and apoptosis of RB cells were analyzed by loss‐of‐function. The underlying mechanism of NEAT1 in RB was mainly focused on the microRNA 204/C‐X‐C chemokine receptor type 4 (miR‐204/CXCR4) axis. In addition, the role and mechanism of NEAT1 in RB were further evaluated in a mouse xenograft tumor model. We found NEAT1 and CXCR4 expression levels were elevated, whereas miR‐204 expression was decreased in RB tissues and cells. Downregulation of NEAT1 significantly decreased the proliferation and migration but promoted the apoptosis of RB cells. NEAT1 functioned as a competing endogenous RNA for miR‐204 to regulate CXCR4 expression. Knockdown of NEAT1 suppressed the tumor volume, tumor weight, and CXCR4 expression, whereas increased miR‐204 expression in mice. In conclusion, NEAT1 promotes the development of RB via miR‐204/CXCR4 axis, which provides a new target for the treatment of RB disease.
EW‐7197 prevents ulcerative colitis‐associated fibrosis and inflammation
Authors: Binabaj Maryam M. , Asgharzadeh Fereshteh , Avan Amir , Rahmani Farzad , Soleimani Atena , Parizadeh Mohammad R. , Ferns Gordon A. , Ryzhikov Mikhail , Khazaei Majid , Hassanian Seyed M. 
Published: November 2018

AbstractEW‐7197 is a transforming growth factor‐β type I receptor kinase inhibitor with potential anti‐inflammatory and antifibrotic properties. Here, we investigate the potential therapeutic effects of EW‐7197 in a murine model of ulcerative colitis. EW‐7197 attenuated the colitis disease activity index by improving rectal bleeding, body weight, and degree of stool consistency. EW‐7197 also reduced colorectal tissue damage and the colon histopathological score by reducing crypt loss, mucosal damage, and tissue inflammation. Moreover, EW‐7197 appeared to ameliorate the inflammatory and fibrotic responses by reducing oxidative stress, reducing submucosal edema and inflammatory cell infiltration, downregulating proinflammatory and pro‐fibrotic genes, and inhibiting excessive collagen deposition in inflamed and fibrotic ulcerative colitis tissues. These results suggest that EW‐7197 has potentially useful therapeutic properties against colitis, with clinically translational potential of inhibiting key pathological responses of inflammation and fibrosis in patients with colitis.
Neonatal and infant diagnostic HIV‐PCR uptake and associations during three sequential policy periods in Cape Town, South Africa: a longitudinal analysis
Authors: Kalk Emma , Kroon Max , Boulle Andrew , Osler Meg , Euvrard Jonathan , Stinson Kathryn , Timmerman Venessa , Davies Mary‐Ann 
Published: November 2018

AbstractIntroductionTo strengthen the early infant diagnosis (EID) programmes and timeously identify and treat HIV‐infected infants, birth HIV‐PCR for some/all infants has been recommended in the Western Cape, South Africa since 2014. Operational data on the implementation of such programmes in low‐ and middle‐income countries are limited.MethodsUtilizing the electronic records platform at primary care facilities, we developed an electronic register which consolidated obstetric and HIV‐related data, allowing us to track a cohort of HIV‐infected/exposed mother/infant dyads longitudinally from antenatal care through delivery to infant HIV‐PCR. We assessed guideline implementation and impact on EID of three sequential EID policies in a referral chain of facilities in Cape Town (primary‐tertiary care). Birth HIV‐PCR was indicated in period 1 if symptomatic; period 2 if meeting high‐risk criteria for transmission; and period 3 for all HIV‐exposed neonates.ResultsWe enrolled 2012 HIV‐exposed infants; 89.2% had at least one HIV‐PCR at any point. The majority of birth tests were performed in hospital versus primary care regardless of policy period. Almost half of all infants (47.9%) had at least one high‐risk criterion for vertical infection; of these, 39.7% had a birth test. Infants with more risk factors were more likely to have birth EID. Receipt of a birth HIV‐PCR significantly reduced the likelihood of receiving a follow‐up test at six to ten weeks, even after adjusting for potential confounders (aOR 0.18 (0.12 to 0.26)). The proportion of infants tested at six to ten weeks old dropped from 92.9% (period 1) to 80.2% in period 3 and those receiving birth HIV‐PCR increased, peaking at 67.4% during period 3. The proportion of positive birth tests was highest (2.9%) when birth tests were restricted to infants meeting high‐risk criteria, with a low proportion positive for the first time at six to ten weeks. During period 3, the proportion positive at six to ten weeks was high (2.4%), highlighting the importance of follow‐up to detect intrapartum and early postpartum infections.ConclusionsOver all policy periods, EID guidelines were incompletely implemented across all levels of care but especially in primary care. Birth HIV‐PCR reduced return for follow‐up testing, such follow‐up testing is critical for the effectiveness of the programme.
Gene expression profiling of human tissue-resident immune cells: Comparing blood and liver
Authors: Boeijen Lauke L , van Oord Gertine W , Hou Jun , van der Heide-Mulder Marieke , Gaggar Anuj , Li Li , Fletcher Simon P , de Knegt Robert J , Boonstra André 
Published: November 2018

Abstract
In this study, we describe a method to reliably characterize intrahepatic leukocyte populations using flow cytometry and next-generation RNA sequencing on fresh human liver biopsies. Over the last decades, immune responses of viral hepatitis patients, and of other liver diseases, have been incompletely characterized. Most studies include peripheral blood samples only, foregoing the possibility to investigate the site of inflammation directly. Here, we show that with an optimized protocol that combines cell sorting and RNA sequencing, we can perform a side by side comparison of both intrahepatic and peripheral immune cells. Using core liver biopsies from chronic hepatitis B virus patients, we show that the expression levels of IFN-stimulated genes and leukocyte-specific genes are markedly different in the liver compartment as compared to the peripheral blood. These observations emphasize the need to sample the liver directly. The variation of gene expression profiles in these chronic hepatitis B patients was considerable, despite the uniform treatment with nucleotide analogs and absence of liver inflammation in these patients. Finally, we show that this method can provide a detailed characterization of previously undetected liver-specific effects of novel candidate therapeutic compounds.
Volatile compounds profiling by using proton transfer reaction‐time of flight‐mass spectrometry (PTR‐ToF‐MS). The case study of dark chocolates organoleptic differences
Authors: Deuscher Zoé , Andriot Isabelle , Sémon Etienne , Repoux Marie , Preys Sébastien , Roger Jean‐Michel , Boulanger Renaud , Labouré Hélène , Le Quéré Jean‐Luc 
Published: November 2018

AbstractDirect‐injection mass spectrometry (DIMS) techniques have evolved into powerful methods to analyse volatile organic compounds (VOCs) without the need of chromatographic separation. Combined to chemometrics, they have been used in many domains to solve sample categorization issues based on volatilome determination. In this paper, different DIMS methods that have largely outperformed conventional electronic noses (e‐noses) in classification tasks are briefly reviewed, with an emphasis on food‐related applications. A particular attention is paid to proton transfer reaction mass spectrometry (PTR‐MS), and many results obtained using the powerful PTR‐time of flight‐MS (PTR‐ToF‐MS) instrument are reviewed. Data analysis and feature selection issues are also summarized and discussed. As a case study, a challenging problem of classification of dark chocolates that has been previously assessed by sensory evaluation in four distinct categories is presented. The VOC profiles of a set of 206 chocolate samples classified in the four sensory categories were analysed by PTR‐ToF‐MS. A supervised multivariate data analysis based on partial least squares regression‐discriminant analysis allowed the construction of a classification model that showed excellent prediction capability: 97% of a test set of 62 samples were correctly predicted in the sensory categories. Tentative identification of ions aided characterisation of chocolate classes. Variable selection using dedicated methods pinpointed some volatile compounds important for the discrimination of the chocolates. Among them, the CovSel method was used for the first time on PTR‐MS data resulting in a selection of 10 features that allowed a good prediction to be achieved. Finally, challenges and future needs in the field are discussed.
Protective effect of silkworm pupa oil on hydrochloric acid/ethanol‐induced gastric ulcers
Authors: Long Xingyao , Zhao Xin , Wang Wei , Zhang Yu , Wang Hongwei , Liu Xinqi , Suo Huayi 
Published: November 2018

AbstractBACKGROUNDSilkworm pupae are a traditional Chinese food, rich in various saturated and unsaturated fatty acids. Unsaturated fatty acids have a certain protective effect against oxidative damage. The present study used an animal model to determine the protective effect of silkworm pupa oil on hydrochloric acid / ethanol‐induced gastric ulcer.RESULTSSilkworm pupa oil is rich in unsaturated fatty acids, including palmitoleic acid 63.4 g kg−1, oleic acid 249.1 g kg−1, linoleic acid 47.0 g kg−1, and linolenic acid 337.8 g kg−1, whereas its unsaturated fatty acid content is 700 g kg−1. Compared to a gastric ulcer control group, high and low doses of pupa oil reduced gastric ulcer area and gastric secretion, whereas gastric pH increased. It also increased serum antioxidant superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH‐Px) levels, somatostatin (SST), and vasoactive intestinal peptide (VIP) levels, and reduced serum interleukin‐6 (IL‐6), interleukin‐12 (IL‐12), tumor necrosis factor (TNF‐α), and interferon‐γ (IFN‐γ), motilin (MTL), and gastrin (GT) levels. RT‐qPCR and western blot analyses indicated that silkworm pupa oil significantly increased CAT, GSH‐Px, epidermal growth factor (EGF), Epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), Cu/Zn‐SOD, Mn‐SOD, and NF‐kappa‐B inhibitor‐α (IκB‐α) expression and lowered nuclear factor‐kappa B (NF‐κB), B‐cell lymphoma‐2 (Bcl‐2), cyclooxygenase‐2 (COX‐2), and inducible nitric oxide synthase (iNOS) expression.CONCLUSIONSilkworm pupa oil treatment reduced oxidative damage and inflammation in mice, and high‐dose silkworm pupa oil was superior to low‐dose silkworm pupa oil, following ranitidine. © 2018 Society of Chemical Industry
Cytotoxicity, antiprotozoal, and anti‐inflammatory activities of eight curry powders and comparison of their UPLC‐ESI‐QTOF‐MS chemical profiles
Authors: Sandjo Louis P , Zingue Stephane , dos Santos Nascimento Marcus VP , de Moraes Milene H , Vicente Geison , Amoah Solomon KS , Dalmarco Eduardo M , Frode Tania S , Creczynski‐Pasa Tânia B , Steindel Mario 
Published: November 2018

ABSTRACTBACKGROUNDCurry powder is a blend of spices that is extensively consumed worldwide and mainly in Central Asia. Its preparation is strictly related to each locality and, because of the health benefits of its constituents, eight commercial forms of this condiment were biologically and chemically investigated. This study aimed to compare their chemical profile as well as their anti‐inflammatory, cytotoxic, and antiparasitic activities.RESULTSCurry samples 1 and 7 inhibited leukocyte influx and myeloperoxidase activity, while only 7 was active on protein exudate and NOx species. 2, 6, and 8 displayed trypanocidal effect against Trypanosoma cruzi amastigote, whereas 6 showed antileishmanial activity on Leishmania amazonensis amastigote. 2, 6, and 8 also inhibited the growth of THP‐1 cells used as the parasite's host. Among the cytotoxic samples (4 and 6), curry sample 6 induced apoptosis in MDA‐MB‐231 cells. Nevertheless, 4 and 6 were unselectively cytotoxic to non‐tumoral and tumoral cells. The anti‐inflammatory, cytotoxicity, and antiparasitic assays were respectively performed by carrageenan‐induced pleurisy test, Alamar blue assay, and intracellular parasite–host cell model. Ultra‐performance liquid chromatographic–electrospray ionization mass spectrometric data from the spices revealed both similar and different metabolites in their composition.CONCLUSIONThe results obtained indicate that different formulations can contribute different health benefits as a result of their chemical composition. © 2018 Society of Chemical Industry
A 96‐hour continuous wound infiltration with ropivacaine reduces analgesic consumption after liver resection: A randomized, double‐blind, controlled trial
Authors: Peres‐Bachelot Véronique , Blanc Ellen , Oussaid Nadia , Pérol David , Daunizeau‐Walker Anne Laure , Pouderoux Stéphanie , Peyrat Patrice , Rivoire Michel , Dupré Aurélien 
Published: November 2018

BackgroundContinuous wound infiltration (CWI) with local anesthetics to reduce morphine consumption in postoperative pain management after open liver resection in patients with cancer.MethodsThis single‐center randomized double‐blind study allocated patients requiring resection of liver metastases to receive a 3.75 mg/mL ropivacaine (ROP) infiltration, followed by a 2 mg/mL ROP CWI, or placebo (P) for 96 hours. Postoperative analgesia included acetaminophen and patient‐controlled analgesia morphine pump. The primary endpoint was to investigate the reduction of total morphine consumption (mg/kg) over the first 96 postoperative hours.ResultsEighty‐five patients were recruited, and randomized (ROP: 42, P: 43) between 2009 and 2014. The median morphine consumption significantly decreased in the ROP arm in the first 96 postoperative hours (ROP: 1.0, P: 1.5 mg/kg;
P = 0.026). Twenty‐three (27%) patients had grade 3 adverse events (ROP: 14, P: 9) and four experienced grade 3 treatment‐related adverse events (ROP: mental confusion [n = 1], hallucinations [n = 2], P: hematoma [n = 1]). Two (5%) patients showed a wound inflammation (ROP: 1, P: 1). Nine (11%) patients experienced at least one serious adverse event (ROP: 6, P: 3); none related to treatment.ConclusionPreperitoneal CWI of 2 mg/mL ROP significantly reduces intravenous morphine consumption during the 96 postoperative hours resulting in an absolute reduction of 0.5 mg/kg.
Assessment of hospital‐level adjusted breast cancer sentinel lymph node positivity rates
Authors: Berger Elizabeth R. , Bilimoria Karl Y. , Kinnier Christine V. , Minami Christina A. , Bethke Kevin P. , Hansen Nora M. , Merkow Ryan P. , Winchester David P. , Yang Anthony D. 
Published: November 2018

Background/ObjectivesProficiency of performing sentinel lymph node biopsy (SLNB) for breast cancer varies among hospitals and may be reflected in the hospital's SLNB positivity rate. Our objectives were to examine whether hospital characteristics are associated with variation in SLNB positivity rates and whether hospitals with lower‐than‐expected SLNB positivity rates have worse patient survival.MethodsUsing the National Cancer Data Base, stage I to III breast cancer patients were identified (2004‐2012). Hospital‐level SLNB positivity rates were adjusted for tumor and patient factors. Hospitals were divided into terciles of SLNB positivity rates (lower‐, higher‐, as‐expected). Hospital characteristics and survival were examined across terciles.ResultsOf 438 610 SLNB patients (from 1357 hospitals), 78 104 had one or more positive SLN (21.3%). Hospitals in the low and high terciles were more likely to be low volume (low: RRR, 4.40; 95% CI, 2.89‐6.57; P < 0.001; and high: RRR, 1.79; 95% CI, 1.21‐2.64; P < 0.001) compared to hospitals with as‐expected (middle tercile) SLNB positivity rates. Stage I patients at low‐ and high‐tercile hospitals had statistically worse survival.ConclusionsThere is a wide variation in hospital SLNB positivity rates. Hospitals with lower‐ or higher‐than‐expected SLNB positivity rates were associated with survival differences. Hospital SLNB positivity rates may be a novel ‘process measure’ to report to hospitals for internal quality assessment.
New lymph node staging for rectal neuroendocrine tumors
Authors: Fields Adam C. , McCarty Justin C. , Ma‐Pak Linda , Lu Pamela , Irani Jennifer , Goldberg Joel E. , Bleday Ronald , Chan Jennifer , Melnitchouk Nelya 
Published: November 2018

Background and ObjectivesCurrent guidelines of the American Joint Commission on Cancer (AJCC) for rectal neuroendocrine tumors (NETs) classify tumor nodal status as N0/N1. This staging does not take into consideration the number of positive lymph nodes. The goal of this study is to determine how the number of positive lymph nodes affects the prognosis for patients with rectal NETs.MethodsThe National Cancer Database was used to identify patients with rectal NETs who underwent rectal resection. Nearest‐neighborhood grouping was used to classify patients by survival to create a new nodal staging system.ResultsThere were 687 patients with rectal NETs. There were distinct 5‐year survival estimates for patients with N0 [81.8% (95%CI:77.1%‐85.6%)], N1 (1‐4 positive lymph nodes) [57.8% (95% confidence interval (CI: 51.2%‐63.9%)] and N2 (≥5 positive lymph nodes) [32.6% (95%CI:25.1%‐40.3%)] patients, P < 0.0001. Distinct 5‐year survival estimates using the new nodal staging system was apparent for patients in the external validation set. After adjusting for predictors of survival in multivariable analysis, the new nodal stage remained an independent predictor of overall survival.ConclusionsThe number of positive locoregional lymph nodes is an independent prognostic factor in rectal NETs. The next AJCC edition should consider classifying patients with rectal NETs as N0, N1, and N2 to provide better estimates of survival for patients.
Validity of Indirect Ultrasound Findings in Acute Anterior Cruciate Ligament Ruptures
Authors: Mautner Ken , Sussman Walter I. , Nanos Katie , Blazuk Joe , Brigham Carmen , Sarros Emily 
Published: November 2018

ObjectivesUltrasound (US) is increasingly being used as an extension of the physical examination on the sidelines, in training rooms, and in clinics. Anterior cruciate ligament (ACL) injury in sport is common, but the literature on US findings after acute ACL rupture is limited. Three indirect US findings of ACL rupture have been described, and this study assessed the validity of these indirect signs.MethodsPatients with an acute knee injury (<6 weeks) underwent US examinations to determine whether there was evidence of a femoral notch sign, posterior cruciate ligament wave sign, or capsular protrusion sign. Ultrasound findings were compared to magnetic resonance imaging.ResultsSixty‐nine patients were included (53 with ACL tears and 16 control patients). The posterior cruciate ligament sign had the highest sensitivity (84.9%), and the notch sign had the highest specificity (93.8%). If 2 or 3 of the signs were positive, the sensitivity was 86.8%, and the specificity was 87.5%.ConclusionsA US examination is an easy‐to‐perform and noninvasive test, and the 3 indirect signs of an acute ACL tear had high positive predictive values ranging from 91.8% to 96.8%.