bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in biocompatibility of microneedles from cyclic olefin polymers with human endothelial and epithelial skin cells
Authors: Schossleitner Klaudia , O'Mahony Conor , Brandstätter Stefan , Haslinger Michael J. , Demuth Sabrina , Fechtig Daniel , Petzelbauer Peter 
Published: November 2018

AbstractMicroneedles are promising devices for transdermal delivery and diagnostic applications, due to their minimally invasive and painless nature of application. However, so far, applications are limited to small scale research projects. Material selection and production for larger projects remain a challenge. In vitro testing using human cell culture could bridge the gap between cost effective screening of suitable materials and concerns for safety and ethics. In this study, materials were tested for effects on viability and morphology of human endothelial cells and keratinocytes. In addition, materials were assessed for their potential to influence cellular differentiation and barrier formation. Elution‐based testing of inflammatory markers revealed no negative effects in all applied tests, whereas the assessment of differentiation markers on cells in direct contact with the material showed differences and allowed the selection of candidate materials for future medical device applications. This study illustrates that elution‐based biocompatibility testing can paint an incomplete picture. Advanced staining techniques and cell types specific for the application of the medical device improve material selection to reduce and replace animal testing at an early stage in the development process. © 2018 The Authors. journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 505–512, 2019.
Efficiency of coculture with angiogenic cells or physiological BMP‐2 administration on improving osteogenic differentiation and bone formation of MSCs
Authors: Zhang Yang , Yang Wanxun , Devit Amar , van den Beucken Jeroen J.J.P. 
Published: November 2018

AbstractCell‐based bone regeneration with mesenchymal stem cells (MSCs) represents the current challenge toward repair of bone defects and fractures. The supposed hurdles for satisfactory performance of cell‐based constructs include inadequate vascularization and osteogenic signals. Considering the reported beneficial role of angiogenic cells in promoting vascularization and osteogenic differentiation and the osteogenic potential of bone morphogenetic protein 2 (BMP‐2), we here evaluated the efficiency of coculture with angiogenic cells or a physiological dose of BMP‐2 on improving osteogenic differentiation of MSCs and bone formation in vivo. In three dimensional (3D) collagen hydrogels in vitro, cocultured human umbilical vein endothelial cells (HUVECs) in a 1:1 ratio or with a physiological dose of BMP‐2 (2 ng/μL) promoted the osteogenic potential of MSCs evidenced by enhanced alkaline phosphatase activity and gene expression of osteogenic markers. Notably, HUVECs evoked similar osteogenic stimulation as BMP‐2, albeit in a delayed manner. When their bone formation capacity was further evaluated in a mouse subcutaneous implantation model, MSCs with BMP‐2 demonstrated the highest efficiency with reproducible bone formation. In contrast, MSCs cocultured with HUVECs constructs displayed substantial blood vessel‐like structures with fibrous tissue rather than ectopic bone as MSC monoculture controls. Our findings confirm the priority of generating cell‐based bone constructs with physiological BMP‐2 administration and indicate the potential of using angiogenic cells to develop vascularized constructs. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 643–653, 2019.
A Heterozygous Splice-Site Mutation in PTHLH Causes Autosomal Dominant Shortening of Metacarpals and Metatarsals
Authors: Reyes Monica , Bravenboer Bert , Jüppner Harald 
Published: November 2018

ABSTRACT

Short metacarpals and/or metatarsals are typically observed in pseudohypoparathyroidism (PHP) type Ia (PHP1A) or pseudo-PHP (PPHP), disorders caused by inactivating GNAS mutations involving exons encoding the alpha-subunit of the stimulatory G protein (Gsα). Skeletal abnormalities similar to those in PHP1A/PPHP were present in several members of an extended Belgian family without evidence for abnormal calcium and phosphate regulation. Direct nucleotide sequencing of genomic DNA from an affected individual (190/III-1) excluded GNAS mutations. Instead, whole exome analysis revealed a novel heterozygous A&gt;G change at nucleotide −3 upstream of PTHLH exon 3 that encodes the last two amino acids of the prosequence and the mature PTHrP. The same nucleotide change was also found in her affected mother and maternal aunt (190/II-2, 190/II-1), and her affected twin sons (190/IV-1, 190/IV-2), but not in her unaffected daughter (190/IV-3) and sister (190/III-2). Complementary DNA derived from immortalized lymphoblastoid cells from 190/IV-2 (affected) and 190/IV-3 (unaffected) was PCR-amplified using forward primers located either in PTHLH exon 1 (noncoding) or exon 2 (presequence and most of the prosequence), and reverse primers located in the 3’-noncoding regions of exons 3 or 4. Nucleotide sequence analysis of these amplicons revealed for the affected son 190/IV-2, but not for the unaffected daughter 190/IV-3, a heterozygous insertion of genomic nucleotides −2 and −1 causing a frameshift after residue 34 of the pre/prosequence and thus 29 novel residues without homology to PTHrP or any other protein. Our findings extend previous reports indicating that PTHrP haploinsufficiency causes skeletal abnormalities similar to those observed with heterozygous GNAS mutations. © 2018 American Society for Bone and Mineral Research.
LncRNA FOXD2‐AS1 accelerates the papillary thyroid cancer progression through regulating the miR‐485‐5p/KLK7 axis
Authors: Zhang Yayuan , Hu Jintao , Zhou Wenbing , Gao Hengyuan 
Published: November 2018

AbstractIt has been proved that long noncoding RNAs (lncRNAs) are important modulators in the tumorigenesis and progression of various malignant tumors. Recently, lncRNA FOXD2‐AS1 has been reported to be an oncogene in several kinds of human cancers. However, the function of FOXD2‐AS1 in papillary thyroid cancer (PTC) has not been well investigated. This study aims to explore the biological role and mechanism of FOXD2‐AS1 in PTC. At first, the expression of FOXD2‐AS1 was examined in PTC tissues and cell lines with quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR). FOXD2‐AS1 was found to observably upregulated in PTC tissues and cell lines. Kaplan‐Meier survival analysis revealed that high expression of FOXD2‐AS1 was closely correlated with the unfavorable prognosis of patients with PTC. Based on the TCGA data set, KLK7 was overexpressed in PTC tumor samples. Our experimental data further validated the upregulation of KLK7 in PTC tissues and cell lines. Similarly, high level of KLKF was associated with poor prognosis of patients with PTC. The positive expression association between FOXD2‐AS1 and KLK7 was analyzed with Pearson correlation coefficient. Loss‐of‐function assays revealed that knockdown of FOXD2‐AS1 or KLK7 greatly inhibited PTC cell proliferation and migration, while induced cell apoptosis. Results of mechanism experiments suggested that FOXD2‐AS1 functioned as a competing endogenous RNA (ceRNA) to enhance the expression of KLK7 by sponging miR‐485‐5p in PTC. Rescue assays were conducted to verify the function of FOXD2‐AS1/miR‐485‐5p/KLK7 axis in PTC progression.
Brain‐derived neurotrophic factor promotes proliferation and progesterone synthesis in bovine granulosa cells
Authors: Chen Shuxiong , Wang Fengge , Liu Zhuo , Zhao Yun , Jiang Yanwen , Chen Lu , Li Chunjin , Zhou Xu 
Published: November 2018

AbstractBrain‐derived neurotrophic factor (BDNF) is involved in regulating the growth of ovarian follicles, maturation of the oocyte, and development of the early embryo through its receptor, tyrosine kinase receptor B (TrkB). However, it is still unclear as to how BDNF influences proliferation and steroidogenesis of bovine granulosa cells (GCs). In this paper, we confirmed that BDNF and TrkB were expressed in bovine GCs, and that proliferation and steroidogenesis by bovine GCs were reduced by knockdown of BDNF or inhibition of TrkB. With respect to GC proliferation, BDNF enhanced cellular viability and the percentage of cells in the S phase. BDNF also activated both protein kinase B (PKB, also known as AKT) and the extracellular signal‐regulated protein kinase 1/2 (ERK1/2)‐signaling pathway. Through the AKT‐signaling pathway, BDNF increased the expression of proliferation‐related genes, including cyclin A1 (CCNA1), cyclin E2 (CCNE2), cyclin D1 (CCND1), and cyclin‐dependent kinase 1 (CDK1). However, through the ERK1/2 signaling pathway, BDNF only increased the expression of CCNA1 and CCNE2. Regarding steroidogenesis by bovine GCs, BDNF promoted progesterone (P
4) synthesis, but had no effect on estradiol; it also activated the AKT‐signaling pathway and increased the expression of steroidogenesis‐related genes, including steroidogenic acute regulatory protein (STAR) and hydroxy‐δ‐5‐steroid dehydrogenase, 3β‐ and steroid δ‐isomerase 1 (HSD3B1). In summary, our data are the first to show that BDNF promotes the proliferation of bovine GCs through TrkB–AKT and ERK1/2 signaling pathways and increases P4 synthesis by bovine GCs through the TrkB–AKT signaling pathway.
New insights into the roles and regulation of SphK2 as a therapeutic target in cancer chemoresistance
Authors: Hasanifard Leili , Sheervalilou Roghayeh , Majidinia Maryam , Yousefi Bahman 
Published: November 2018

AbstractChemoresistance is a complicated process developed by most cancers and accounts for the majority of relapse and metastasis in cancer. The main mechanisms of chemoresistance phenotype include increased expression and/or activated drug efflux pumps, altered DNA repair, altered metabolism of therapeutics as well as impaired apoptotic signaling pathways. Aberrant sphingolipid signaling has also recently received considerable attention in chemoresistance. Sphingolipid metabolites regulate main biological processes such as apoptosis, cell survival, proliferation, and differentiation. Two sphingosine kinases, SphK1 and SphK2, convert sphingosine to sphingosine‐1‐phosphate, an antiapoptotic bioactive lipid mediator. Numerous evidence has revealed the involvement of activated SphK1 in tumorigenesis and resistance, however, contradictory results have been found for the role of SphK2 in these functions. In some studies, overexpression of SphK2 suppressed cell growth and induced apoptosis. In contrast, some others have shown cell proliferation and tumor promotion effect for SphK2. Our understanding of the role of SphK2 in cancer does not have a sufficient integrity. The main focus of this review will be on the re‐evaluation of the role of SphK2 in cell death and chemoresistance in light of our new understanding of molecular targeted therapy. We will also highlight the connections between SphK2 and the DNA damage response. Finally, we will provide our insight into the regulatory mechanisms of SphKs by two main categories, micro and long, noncoding RNAs as the novel players of cancer chemoresistance.
Inhibitory effect of MSH6 gene silencing in combination with cisplatin on cell proliferation of human osteosarcoma cell line MG63
Authors: Liu Hu‐Cheng , Zeng Jin , Zhang Bin , Liu Xu‐Qiang , Dai Min 
Published: November 2018

AbstractOsteosarcoma (OS) is one of the most common primary bone malignancies, with the survival rate of patients with OS remaining low. Therefore, we conducted this study to identify the potential role combination of both MSH6 gene silencing and cisplatin (DDP) plays in OS cell proliferation and apoptosis. Microarray‐based gene expression profiling was used to identify the differentially expressed genes (DEGs) in patients with OS, as well as microRNAs (miRNAs) that regulate the candidate gene. OS tissues from 67 patients with OS along with normal tissues from 24 amputee patients were collected for detection of the positive expression of mutS homolog 6 (MSH6) protein, mRNA, and protein expressions of c‐myc, cyclin D1, l‐2, B‐cell lymphoma 2 (Bcl‐2), Stathmin, proliferating cell nuclear antigen (PCNA), and Bcl‐2‐associated X (Bax). Moreover, after MSH6 silencing and DDP were treated on the selected human OS cell line MG63 with the highest expression of MSH6, cell viability, cell cycle distribution, and apoptosis were detected. The microarray analysis showed that MSH6 was upregulated in OS chip data. Furthermore, silencing MSH6 combined with DDP reduced expressions of c‐myc, cyclin D1, Bcl‐2, Stathmin, and PCNA, and elevated Bax expression, whereas inhibiting OS cell viability, impeding cell cycle distribution, and inducing apoptosis. In conclusion, our preliminary results indicated that the combination of MSH6 gene silencing coupled with DDP may have a better effect on the inhibition of OS cell proliferation and promote apoptosis, potentially providing targets for the OS treatment.
Inflammatory molecules produced by meniscus and synovium in early and end‐stage osteoarthritis: a coculture study
Authors: Favero Marta , Belluzzi Elisa , Trisolino Giovanni , Goldring Mary B , Goldring Steven R , Cigolotti Augusto , Pozzuoli Assunta , Ruggieri Pietro , Ramonda Roberta , Grigolo Brunella , Punzi Leonardo , Olivotto Eleonora 
Published: November 2018

AbstractThe aim of this study was to identify the molecules and pathways involved in the cross‐talk between meniscus and synovium that may play a critical role in osteoarthritis (OA) pathophysiology. Samples of synovium and meniscus were collected from patients with early and end‐stage OA and cultured alone or cocultured. Cytokines, chemokines, metalloproteases, and their inhibitors were evaluated at the gene and protein levels. The extracellular matrix (ECM) changes were also investigated. In early OA cultures, higher levels of interleukin‐6 (IL‐6) and IL‐8 messenger RNA were expressed by synovium and meniscus in coculture compared with meniscus cultured alone. RANTES release was significantly increased when the two tissues were cocultured compared with meniscus cultured alone. Increased levels of matrix metalloproteinase‐3 (MMP‐3) and MMP‐10 proteins, as well as increased release of glycosaminoglycans and aggrecan CS846 epitope, were observed when synovium was cocultured with meniscus. In end‐stage OA cultures, increased levels of IL‐8 and monocyte chemoattractant protein‐1 (MCP‐1) proteins were released in cocultures compared with cultures of meniscus alone. Chemokine (C‐C motif) ligand 21 (CCL21) protein release was higher in meniscus cultured alone and in coculture compared with synovium cultured alone. Increased levels of MMP‐3 and 10 proteins were observed when tissues were cocultured compared with meniscus cultured alone. Aggrecan CS846 epitope release was increased in cocultures compared with cultures of either tissue cultured alone. Our study showed the production of inflammatory molecules by synovium and meniscus which could trigger inflammatory signals in early OA patients, and induce ECM loss in the progressive and final stages of OA pathology.
The association between physician's affiliation and patients’ adherence to their antihypertensive medication and pharmaceutical knowledge
Authors: Matsumura Shinji , Watanabe Kazuhiro , Fukuhara Shunichi 
Published: November 2018

AbstractBackgroundThe aim of this study was to examine whether or not the type of physician is associated with the knowledge of and adherence to hypertensive medication among patients.MethodsThe study was a self‐administered questionnaire survey among patients who submitted their prescriptions for antihypertensive drugs to 13 pharmacies in Japan in 2006. We compared patients’ knowledge of their medications and the self‐reported adherence according to the type of physician.ResultsA total of 736 patients were surveyed, and 687 (362 from clinics and 325 from hospitals) were analyzed. In total, 51.8% of the patients correctly named their antihypertensive medicine, with no significant differences observed between clinics and hospitals (51.4% in clinics vs 52.3% in hospitals; P = 0.81, adjusted odds ratio (OR) to the hospital: 0.736, 95% confidence interval [CI]: 0.50‐1.08). Significant differences were not observed in the knowledge of the frequency with which hypertensive medication was supposed to be taken (47.2% in clinics vs 46.5% in hospitals; P = 0.84, adjusted OR: 0.80, 95% CI: 0.55‐1.16), nor observed in the knowledge of the side effects of the medication (53.2% in clinics vs 51.0% in hospitals; P = 0.57, adjusted OR: 1.14, 95% CI: 0.78‐1.68). No significant difference was observed in self‐reported adherence (75.1% in clinics vs 77.7% in hospitals; P = 0.42, adjusted OR: 0.73, 95% CI: 0.46‐1.16).ConclusionsAbout 75% answered that they were taking their medication as instructed. No significant differences were observed in responses based on the physician's affiliation. Further studies are needed to achieve better patient's adherence and pharmaceutical knowledge.
Nonrepetitive colorings of graphs excluding a fixed immersion or topological minor
Authors: Wollan Paul , Wood David R. 
Published: November 2018

AbstractWe prove that graphs excluding a fixed immersion have bounded nonrepetitive chromatic number. More generally, we prove that if is a fixed planar graph that has a planar embedding with all the vertices with degree at least 4 on a single face, then graphs excluding as a topological minor have bounded nonrepetitive chromatic number. This is the largest class of graphs known to have bounded nonrepetitive chromatic number.
Innate-like B cell subsets during immune responses: Beyond antibody production
Authors: Romero-Ramírez Sandra , Navarro-Hernandez Itze C , Cervantes-Díaz Rodrigo , Sosa-Hernández Víctor A , Acevedo-Ochoa Ernesto , Kleinberg-Bild Ari , Valle-Rios Ricardo , Meza-Sánchez David E , Hernández-Hernández José M , Maravillas-Montero José L 
Published: November 2018

Abstract
B lymphocytes are recognized for their crucial role in the adaptive immunity since they represent the only leukocyte lineage capable of differentiating into Ab-secreting cells. However, it has been demonstrated that these lymphocytes can exert several Ab-independent functions, including engulfing and processing Ags for presentation to T cells, secreting soluble mediators, providing co-stimulatory signals, and even participating in lymphoid tissues development. Beyond that, several reports claiming the existence of multiple B cell subsets contributing directly to innate immune responses have appeared. These “innate-like” B lymphocytes, whose phenotype, development pathways, tissue distribution, and functions are in most cases notoriously different from those of conventional B cells, are crucial to early protective responses against pathogens by exerting “crossover” defensive strategies that blur the established boundaries of innate and adaptive branches of immunity. Examples of these mechanisms include the rapid secretion of the polyspecific natural Abs, increased susceptibility to innate receptors-mediated activation, cytokine secretion, downstream priming of other innate cells, usage of specific variable immunoglobulin gene-segments, and other features. As these new insights emerge, it is becoming preponderant to redefine the functionality of B cells beyond their classical adaptive-immune tasks.
Medially‐stabilized total knee arthroplasty does not alter knee laxity and balance in cadaveric knees
Authors: Hall Rachel K. , Ewing Joseph A. , Beal Matthew D. , Manning David W. , Siston Robert A. 
Published: November 2018

ABSTRACTInstability after total knee arthroplasty (TKA) can lead to suboptimal outcomes and revision surgery. Medially‐stabilized implants aim to more closely replicate normal knee motion than other implants following TKA, but no study has investigated knee laxity (motion under applied loads) and balance (i.e., difference in varus/valgus motion under load) following medially‐stabilized TKA. The primary purposes of this study were to investigate how medially‐stabilized implants change knee laxity in non‐arthritic, cadaveric knees, and if it produces a balanced knee after TKA. Force‐displacement data were collected on 18 non‐arthritic cadaveric knees before and after arthroplasty using medially‐stabilized implants. Varus‐valgus and anterior‐posterior laxity and varus‐valgus balance were compared between native and medially‐stabilized knees at 0°, 20°, 60°, and 90° under three different loading conditions. Varus‐valgus and anterior‐posterior laxities were not different between native and medially‐stabilized knees under most testing conditions (p ≥ 0.068), but differences of approximately 2° less varus‐valgus laxity at 20° of flexion and 4 mm more anterior‐posterior laxity at 90° were present from native laxities (p < 0.017) Medially‐stabilized implant balance had ≤1.5° varus bias at all flexion angles. Future studies should confirm if the consistent laxity afforded by the medially‐stabilized implant is associated with better and more predictable postoperative outcomes. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:335–349, 2019.
Polymerization‐Induced Thermal Self‐Assembly of Functional and Thermo‐Responsive Diblock Copolymer Nano‐Objects via RAFT Aqueous Polymerization
Authors: Vakili Mohammad , Cunningham Victoria J. , Trebbin Martin , Theato Patrick 
Published: November 2018

AbstractThe polymerization‐induced self‐assembly (PISA) of amphiphilic diblock copolymer nano‐objects, which are synthesized via reversible addition‐fragmentation chain‐transfer (RAFT) aqueous polymerization, is discussed. First, the effectiveness of the (S)‐2‐(ethyl propionate)‐(O‐ethyl xanthate) as a RAFT chain transfer agent for the polymerization of N,N‐dimethylacrylamide (DMAm) yielding a water‐soluble macro RAFT agent is investigated. In a second step, poly(DMAm) macro‐CTA is chain‐extended with acrylate monomers in water inducing a PISA process. Besides the use of pentafluorophenyl acrylate (PFPA) as core‐forming block, the thermo‐responsive nature of N‐isopropylacrylamide (NIPAm) and the reactive character of pentafluorophenyl acrylate (PFPA) for a subsequent post‐modification is exploited. Monomer conversion and reaction kinetics are determined via nuclear magnetic resonance spectroscopy, while gel permeation chromatography is used to evaluate the molecular weight distribution of the polymers. The obtained spherical nanostructures are analyzed via dynamic light scattering, scanning electron microscopy, transmission electron microscopy and atomic force microscopy.
Remarks on the NIP in a model
Authors: Khanaki Karim , Pillay Anand 
Published: November 2018

AbstractWe define the notion has the NIP (not the independence property) in A, where A is a subset of a model, and give some equivalences by translating results from function theory. We also discuss the number of coheirs when A is not necessarily countable, and revisit the notion “ has the NOP (not the order property) in a model M”.