bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exendin‐4(Lys27PAL)/gastrin/xenin‐8‐Gln: A novel acylated GLP‐1/gastrin/xenin hybrid peptide that improves metabolic status in obese‐diabetic (ob/ob) mice
Authors: Hasib Annie , Ng Ming T. , Tanday Neil , Craig Sarah L. , Gault Victor A. , Flatt Peter R. , Irwin Nigel 
Published: November 2018

AbstractBackgroundTherapeutic benefits of peptide‐based drugs is limited by rapid renal elimination.MethodsTherefore, to prolong the biological action profile of the recently characterized triple‐acting hybrid peptide, exendin‐4/gastrin/xenin‐8‐Gln, a fatty acid (C‐16) has been covalently attached, creating exendin‐4(Lys27PAL)/gastrin/xenin‐8‐Gln. Exendin‐4/gastrin and liraglutide/gastrin/xenin‐8‐Gln were also synthesized as direct comparator peptides.ResultsAll hybrid peptides evoked significant concentration‐dependent increases of insulin secretion from isolated murine islets and BRIN‐BD11 cells. Following administration of peptides with glucose to mice, all hybrids significantly reduced the overall glycaemic excursion and increased insulin concentrations. In contrast to other treatments, exendin‐4(Lys27PAL)/gastrin/xenin‐8‐Gln displayed impressive antihyperglycaemic actions even 12 hours after administration, highlighting protracted duration of effects. Exendin‐4/gastrin/xenin‐8‐Gln, exendin‐4/gastrin, and exendin‐4(Lys27PAL)/gastrin/xenin‐8‐Gln were then progressed to a 31‐day twice‐daily treatment regimen in obese‐diabetic ob/ob mice. All treatments decreased nonfasting glucose and HbA1c concentrations, as well as enhancing circulating and pancreatic insulin levels. Exendin‐4/gastrin and exendin‐4/gastrin/xenin‐8‐Gln also decreased food intake. Glucose tolerance was improved by all treatments, but only exendin‐4(Lys27PAL)/gastrin/xenin‐8‐Gln augmented glucose‐induced insulin secretion. Interestingly, treatment regimens that included a xenin component induced clear advantages on the metabolic response to glucose‐dependent insulinotropic polypeptide (GIP) and the glucose‐lowering actions of insulin.ConclusionThis study emphasizes the therapeutic promise of long‐acting, multi‐targeting hybrid gut peptides for type 2 diabetes.
Gene flow improves fitness at a range edge under climate change
Authors: Bontrager Megan , Angert Amy L. 
Published: November 2018

AbstractPopulations at the margins of a species' geographic range are often thought to be poorly adapted to their environment. According to theoretical predictions, gene flow can inhibit these range edge populations if it disrupts adaptation to local conditions. Alternatively, if range edge populations are small or isolated, gene flow can provide beneficial genetic variation and may facilitate adaptation to environmental change. We tested these competing predictions in the annual wildflower Clarkia pulchella using greenhouse crosses to simulate gene flow from sources across the geographic range into two populations at the northern range margin. We planted these between-population hybrids in common gardens at the range edge and evaluated how genetic differentiation and climatic differences between edge populations and gene flow sources affected lifetime fitness. During an anomalously warm study year, gene flow from populations occupying historically warm sites improved fitness at the range edge and plants with one or both parents from warm populations performed best. The effects of the temperature provenance of gene flow sources were most apparent at early life history stages, but precipitation provenance also affected reproduction. We also found benefits of gene flow that were independent of climate: after climate was controlled for, plants with parents from different populations performed better at later lifestages than those with parents from the same population, indicating that gene flow may improve fitness via relieving homozygosity. Further supporting this result, we found that increasing genetic differentiation of parental populations had positive effects on fitness of hybrid seeds. Gene flow from warmer populations, when it occurs, is likely to contribute adaptive genetic variation to populations at the northern range edge as the climate warms. On heterogeneous landscapes, climate of origin may be a better predictor of gene flow effects than geographic proximity.
Activated T cells induce proliferation of oligodendrocyte progenitor cells via release of vascular endothelial cell growth factor‐A
Authors: Choi Elliot H. , Xu Yadi , Medynets Marie , Monaco Maria Chiara G. , Major Eugene O. , Nath Avindra , Wang Tongguang 
Published: November 2018

AbstractNeuroinflammatory diseases such as multiple sclerosis are characterized by infiltration of lymphocytes into the central nervous system followed by demyelination and axonal degeneration. While evidence suggests that activated T lymphocytes induce neurotoxicity and impair function of neural stem cells, the effect of T cells on oligodendrocyte progenitor cells (OPCs) is still uncertain, partly due to the difficulty in obtaining human OPCs. Here we studied the effect of activated T cells on OPCs using OPCs derived from human hematopoietic stem cells or from human fetal brain. OPCs were exposed to supernatants (sups) from activated T cells. Cell proliferation was determined by EdU incorporation and CellQuanti‐Blue assays. Surprisingly, we found that sups from activated T cells induced OPC proliferation by regulating cell cycle progression. Vascular endothelial growth factor A (VEGF‐A) transcripts were increased in T cells after activation. Immunodepletion of VEGF‐A from activated T cell sups significantly attenuated its effect on OPC proliferation. Furthermore, VEGF receptor 2 (VEGFR2) was expressed on OPCs and its inhibition also attenuated activated T cell‐induced OPC proliferation. Thus, activated T cells have a trophic role by promoting OPC proliferation via the VEGFR2 pathway.
Metal wear particles in hematopoietic marrow of the axial skeleton in patients with prior revision for mechanical failure of a hip or knee arthroplasty
Authors: Hall Deborah J. , Pourzal Robin , Jacobs Joshua J. , Urban Robert M. 
Published: November 2018

AbstractWear particles generated by hip and knee arthroplasties disseminate to the liver and spleen with the highest concentrations observed in subjects who have had a failed arthroplasty. We asked to what extent metallic particles could also disseminate to remote hematopoietic bone marrow. Cored samples of red marrow from the axial skeleton and proximal humerus were obtained postmortem from four males and two females aged 79–92 years. Seven to seventeen years prior to their demise, each subject had undergone successful revision of their arthroplasty for mechanical failure in which an unintended wear condition had generated a large volume of metal particles. The marrow samples were analyzed using stained histological sections and energy dispersive X‐ray analysis. Intracellular metal alloy particles were detected in the bone marrow of the cranium, proximal humerus, sternum, ribs, lumbar vertebrae, and the iliac crest. The components previously revised for mechanical failure were confirmed to be the predominant source of the disseminated wear debris. Particles of either Ti, Ti6Al4V, CoCrMo, FeCrNi alloys, or BaSO4 were identified in 24 of the 25 marrow samples examined. The particles ranged in size from 50 nm (the limit of resolution of our technique) to 6 μm. Metallic wear particles generated by hip and knee arthroplasties can disseminate widely to hematopoietic bone marrow throughout the axial skeleton and proximal humerus, especially in cases with a history of severe wear. The hematopoietic microenvironment is potentially sensitive to metallic degradation products. However, actual medical sequelae from disseminated wear debris is a rare occurrence. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1930–1936, 2019.
PDGF Modulates BMP2‐Induced Osteogenesis in Periosteal Progenitor Cells
Authors: Wang Xi , Matthews Brya G , Yu Jungeun , Novak Sanja , Grcevic Danka , Sanjay Archana , Kalajzic Ivo 
Published: November 2018

ABSTRACTBMPs are used in various clinical applications to promote bone formation. The limited success of the BMPs in clinical settings and supraphysiological doses required for their effects prompted us to evaluate the influence of other signaling molecules, specifically platelet‐derived growth factor (PDGF) on BMP2‐induced osteogenesis. Periosteal cells make a major contribution to fracture healing. We detected broad expression of PDGF receptor beta (PDGFRβ) within the intact periosteum and healing callus during fracture repair. In vitro, periosteum‐derived progenitor cells were highly responsive to PDGF as demonstrated by increased proliferation and decreased apoptosis. However, PDGF blocked BMP2‐induced osteogenesis by inhibiting the canonical BMP2/Smad pathway and downstream target gene expression. This effect is mediated via PDGFRβ and involves ERK1/2 MAPK and PI3K/AKT signaling pathways. Therapeutic targeting of the PDGFRβ pathway in periosteum‐mediated bone repair might have profound implications in the treatment of bone disease in the future. © 2018 The Authors JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
Overexpression of FOXS1 in gastric cancer cell lines inhibits proliferation, metastasis, and epithelial‐mesenchymal transition of tumor through downregulating wnt/β‐catenin pathway
Authors: Lu Qiyu , Ma Xudong , Li Yijun , Song Wanhong , Zhang Lingshu , Shu Yixiong , Wan Baosheng 
Published: November 2018

AbstractBackgroundExpression of forkhead box (FOX) superfamily members has been shown to be decreased in cancer, which was linked to poor prognosis of patients. The aim of this study was to investigate the expression of a new FOX superfamily member, FOXS1, in gastric cancer, and the influence of FOXS1 overexpression on the tumorigenesis of gastric cancer cells. The underlying molecular mechanism was also investigated.Materials and MethodsFOXS1 expression levels were firstly measured in 15 paired gastric cancer and peritumor tissue using quantitative polymerase chain reaction or immunohistochemistry. Secondly, FOXS1 overexpression models were established in two gastric cancer cell lines (SNU‐216 and AGS) and FOXS1 knockdown model was established in SNU‐638 gastric cancer cell line. Markers for cell proliferation, metastasis, cell cycle status, and wnt/β‐catenin pathway were evaluated. Influence of FOXS1 overexpression on tumorigenesis was further evaluated in xenograft model.ResultsExpression of FOXS1 was significantly decreased in gastric cancer tissue in both messenger RNA and protein levels, compared with peritumor tissue. Our results showed that compared to cell lines transfected with negative control, gastric cancer cell lines with FOXS1 overexpression showed suppressed cell proliferation, metastasis, and increased ratio of G0/G1 phase. Xenograft model also showed suppressed tumor growth in FOXS1 overexpression group. Epithelial‐mesenchymal transition was also inhibited when FOXS1 was overexpressed, which was indicated by an increase of E‐cadherin expression and decrease in vimentin expression. Further investigation showed that expression of β‐catenin was decreased, together with decreased expression in downstream signaling factors, c‐Myc and cyclin‐D1 in FOXS1 overexpression cell lines. On the other hand, knockdown of FOXS1 showed opposite trends in the changes of those markers for cell proliferation, metastasis, cell cycle status, and wnt/β‐catenin pathway, compared with FOXS1 overexpression.ConclusionIn conclusion, the present study showed that FOXS1 expression is downregulated in most GC cases in our cohort, and this loss of expression may promote cell proliferation and metastasis through upregulation of wnt/β‐catenin pathway.
miR‐146b overexpression ameliorates lipopolysaccharide‐induced acute lung injury in vivo and in vitro
Authors: He Ruoxi , Li Ying , Zhou Li , Su Xiaoli , Li Yuanyuan , Pan Pinhua , Hu Chengping 
Published: November 2018

AbstractAcute respiratory distress syndrome (ARDS) is a type of acute lung injury (ALI), which causes high morbidity and mortality. So far, effective clinical treatment of ARDS is still limited. Recently, miR‐146b has been reported to play a key role in inflammation. In the present study, we evaluated the functional role of miR‐146b in ARDS using the murine model of lipopolysaccharide (LPS)‐induced ALI. The miR‐146b expression could be induced by LPS stimulation, and miR‐146b overexpression was required in the maintenance of body weight and survival of ALI mice; after miR‐146b overexpression, LPS‐induced lung injury, pulmonary inflammation, total cell and neutrophil counts, proinflammatory cytokines, and chemokines in bronchial alveolar lavage (BAL) fluid were significantly reduced. The promotive effect of LPS on lung permeability through increasing total protein, albumin and IgM in BAL fluid could be partially reversed by miR‐146b overexpression. Moreover, in murine alveolar macrophages, miR‐146b overexpression reduced LPS‐induced TNF‐α and interleukin (IL)‐1β releasing. Taken together, we demonstrated that miR‐146b overexpression could effectively improve the LPS‐induced ALI; miR‐146b is a promising target in ARDS treatment.
Nobiletin suppresses high‐glucose–induced inflammation and ECM accumulation in human mesangial cells through STAT3/NF‐κB pathway
Authors: Liu Zhenzhou , Han Yanru , Zhao Fucheng , Zhao Zhenxia , Tian Junlei , Jia Kui 
Published: November 2018

AbstractDiabetic nephropathy (DN) is a complication of chronic diabetes and the main cause of end‐stage renal disease all over the world. Inflammation and extracellular matrix (ECM) accumulation play important roles in the pathogenesis of DN. Evidence suggested that nobiletin acts anti‐inflammatory role and plays a critical role in diabetes; however, its role in DN remains unclear. In the current study, we promulgated the nobiletin involved in high‐glucose–induced glomerular mesangial cell inflammation and ECM accumulation. Nobiletin treatment significantly abrogated high‐glucose–induced glomerular mesangial cell proliferation. Nobiletin treatment markedly suppressed inflammation cytokine secretion, including interleukin (IL)‐1β, IL‐6, tumor necrosis factor α, and monocyte chemoattractant protein 1 in high‐glucose–induced glomerular mesangial cell. Also, exposed nobiletin to high‐glucose–induced glomerular mesangial cell considerably reduced ECM accumulation through inhibited ECM‐associated protein type 4 collagen and fibronectin expression. Furthermore, nobiletin treatment abolished nuclear factor κB (NF‐κB) pathway activation through signal transducer and activator of transcription 3 (STAT3) inhibition. Overexpression STAT3 reversed the effects of nobiletin on high‐glucose–induced glomerular mesangial cell proliferation, inflammation, ECM accumulation, and NF‐κB pathway activation. Hence, our results suggest that nobiletin play roles in high‐glucose‐induced glomerular mesangial cells through inhibiting inflammation and ECM accumulation, and the STAT3/NF‐κB pathway was involved in the function of nobiletin.
Self‐stigma and the mediating impact of the “why try” effect on depression
Authors: Corrigan Patrick W. , Nieweglowski Katherine , Sayer Janis 
Published: November 2018

AbstractThe “why try” effect, a consequence of self‐stigma, is a sense of behavioral futility that may worsen depression. This study examines the regressive model of self‐stigma, the factor structure of a why try measure, and the pathway through which self‐stigma leads to depression. Data from 291 people self‐identifying with mental illness were collected through an online survey. Participants completed the Why Try Stigma Scale (WTSS) and measures of self‐stigma and depression. Structural equation modeling was used to test the WTSS factor structure and path models. Reducing the WTSS from 12 to 6 items led to good fit. The regressive model of self‐stigma was validated. A good fit was demonstrated for a model in which harm leads to unworthiness, then incapability, and then depression. The regressive model worsens sense of worthiness, which in turn affects personal capability, resulting in increased depression.
Suicide risk and social support in Australian resource sector employees: A cross‐sectional study
Authors: Miller P. , Brook L. , Stomski N.J. , Ditchburn G. , Morrison P. 
Published: November 2018

AbstractThis study examines the association between suicide risk and social support in Australian resource sector employees. We included 150 participants, who completed the Beck Hopelessness Scale and MOS‐Social Support Survey. Data were analyzed using smallest space analysis and multidimensional scalogram analysis. The analysis identified four distinct regions, which were conceptualized as “confiding,” “affection,” “companionship,” and “practical help.” All of these components of social support were associated with hopelessness, which has important clinical implications as hopelessness is related to suicide risk. The results of this study also demonstrated that lower levels of social support, and greater sense of perceived hopelessness tended to lead to Australian resource workers seeking assistance from mental health professionals in the previous year. Attention should turn towards providing interventions that promote social support for employees in Australian resource industry.
Facilitating community connections among people with mental illnesses: Perspectives from grassroots community leaders
Authors: Bromage Billy , Barrenger Stacey L. , Clayton Ashley , Rowe Michael , Williamson Bridgett , Benedict Patricia , Kriegel Liat S. 
Published: November 2018

AbstractWe conducted focus groups comprising 20 grassroots community leaders to identify social and structural elements that affect community engagement among people with serious mental illnesses. Community leaders not affiliated with mental health systems have been mostly left out of the discussions about inclusion and engagement, even though they possess unique information about the places where they live and can be essential partners in making community connections. The findings from the focus groups point to elements that both facilitate and inhibit connections, as well as roles community mental health practitioners may take on, to engage with community leaders and people with mental illness to minimize barriers and foster connections in community settings. Additionally, the focus groups elucidated the interplay between the right to be a member of one's community and a community's responsibility to create a welcoming environment. The current study garnered information regarding the broader needs and implications of community connections, as well as some specific suggestions to enhance community engagement among people with serious mental illness. Hesitation and stigma around engaging individuals with mental illnesses were identified as barriers to inclusion. Further study about how community leaders and groups may be involved in facilitating meaningful community connections is recommended.
microRNA‐186 inhibition of PI3K–AKT pathway via SPP1 inhibits chondrocyte apoptosis in mice with osteoarthritis
Authors: Lin Zeng , Tian Xin‐Yi , Huang Xi‐Xi , He Ling‐Li , Xu Feng 
Published: November 2018

AbstractChondrocyte apoptosis has been implicated as a major pathological osteoarthritis (OA) change in humans and experimental animals. We evaluate the ability of miR‐186 on chondrocyte apoptosis and proliferation in OA and elucidate the underlying mechanism concerning the regulation of miR‐186 in OA. Gene expression microarray analysis was performed to screen differentially expressed messenger RNAs (mRNAs) in OA. To validate the effect of miR‐186 on chondrocyte apoptosis, we upregulated or downregulated endogenous miR‐186 using mimics or inhibitors. Next, to better understand the regulatory mechanism for miR‐186 governing SPP1, we suppressed the endogenous expression of SPP1 by small interfering RNA (siRNA) against SPP1 in chondrocytes. We identified SPP1 is highly expressed in OA according to an mRNA microarray data set GSE82107. After intra‐articular injection of papain into mice, the miR‐186 is downregulated while the SPP1 is reciprocal, with dysregulated PI3K–AKT pathway in OA cartilages. Intriguingly, miR‐186 was shown to increase chondrocyte survival, facilitate cell cycle entry in OA chondrocytes, and inhibit chondrocyte apoptosis in vitro by modulation of pro‐ and antiapoptotic factors. The determination of luciferase activity suggested that miR‐186 negatively targets SPP1. Furthermore, we found that the effect of miR‐186 suppression on OA chondrocytes was lost when SPP1 was suppressed by siRNA, suggesting that miR‐186 affected chondrocytes by targeting and depleting SPP1, a regulator of PI3K–AKT pathway. Our findings reveal a novel mechanism by which miR‐186 inhibits chondrocyte apoptosis in OA by interacting with SPP1 and regulating PI3K–AKT pathway. Restoring miR‐186 might be a future therapeutic strategy for OA.
Leukemia therapy by flavonoids: Future and involved mechanisms
Authors: Saraei Raedeh , Marofi Faroogh , Naimi Adel , Talebi Mehdi , Ghaebi Mahnaz , Javan Naser , Salimi Omid , Hassanzadeh Ali 
Published: November 2018

AbstractFlavonoids are a varied family of phytonutrients (plant chemicals) usually are detected in fruits and vegetables. In this big family, there exist more than 10,000 members that is separated into six chief subtypes: isoflavonols, flavonoenes, flavones, flavonols, anthocyanins, and chalcones. The natural compounds, such as fruits, have visible positive effects in regulating of survival involved signaling pathways that performance as the regulator of cell survival, growth, and proliferation. Researchers have established that commonly consumption up flavonoids decreases incidence and development risk of certain cancers, especially leukemia. Flavonoids have been able to induce apoptosis and stimulate cell cycle arrest in cancer cells via different pathways. Similarly, they have antiangiogenesis and antimetastasis capability, which were shown in wide ranges of cancer cells, particularly, leukemia. It seems that flavonoid because of their widespread approval, evident safety and low rate of side effects, have hopeful anticarcinogenic potential for leukemia therapy. Based on the last decade reports, the most important acting mechanisms of these natural compounds in leukemia cells are stimulating of apoptosis pathways by upregulation of caspase 3, 8, 9 and poly ADP‐ribose polymerase (PARP) and proapoptotic proteins, particularly Bax activation. As well, they can induce cell cycle arrest in target cells not only via increasing of activated levels of p21 and p53 but also by inhibition of cyclins and cyclin‐dependent kinases. Furthermore, attenuation of neclear factor‐κB and signal transducer and activator of transcription 3 activation, suppression of signaling pathway and downregulation of intracellular antiapoptotic proteins are other significant antileukemic function mechanism of flavonoids. Overall, it appears that flavonoids are promising and effective compounds in the field of leukemia therapy. In this review, we tried to accumulate and revise most promising flavonoids and finally declared their major working mechanisms in leukemia cells.