bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of EP2 receptor suppresses poly(I: C) and LPS‐mediated inflammation in primary microglia and organotypic hippocampal slice cultures: Contributing role for MAPKs
Authors: Yousif Nizar M. , de Oliveira Antonio Carlos Pinheiro , Brioschi Simone , Huell Michael , Biber Knut , Fiebich Bernd L.
Published: December 2017

Brain inflammation is a critical factor involved in neurodegeneration. Recently, the prostaglandin E2 (PGE2) downstream members were suggested to modulate neuroinflammatory responses accompanying neurodegenerative diseases. In this study, we investigated the protective effects of prostaglandin E2 receptor 2 (EP2) during TLR3 and TLR4‐driven inflammatory response using in vitro primary microglia and ex vivo organotypic hippocampal slice cultures (OHSCs). Depletion of microglia from OHSCs differentially affected TLR3 and TLR4 receptor expression. Poly(I:C) induced the production of prostaglandin E2 in OHSCs by increasing cyclooxygenase (COX‐2) and microsomal prostaglandin E synthase (mPGES)‐1. Besides, stimulation of OHSCs and microglia with Poly(I:C) upregulated EP2 receptor expression. Co‐stimulation of OHSCs and microglia with the EP2 agonist butaprost reduced inflammatory mediators induced by LPS and Poly(I:C). In Poly(I:C) challenged OHSCs, butaprost almost restored microglia ramified morphology and reduced Iba1 immunoreactivity. Importantly, microglia depletion prevented the induction of inflammatory mediators following Poly(I:C) or LPS challenge in OHSCs. Activation of EP2 receptor reversed the Poly(I:C)/LPS‐induced phosphorylation of the mitogen activated protein kinases (MAPKs) ERK, p38 MAPK and c‐Jun N‐terminal kinase (JNK) in microglia. Collectively, these data identify an anti‐inflammatory function for EP2 signaling in diverse innate immune responses, through a mechanism that involves the mitogen‐activated protein kinases pathway.
Fasting induces astroglial plasticity in the olfactory bulb glomeruli of rats
Authors: Daumas‐Meyer Virginie , Champeil‐Potokar Gaëlle , Chaumontet Catherine , Dahirel Patrice , Papillon Catherine , Congar Patrice , Denis Isabelle
Published: December 2017

The detection of food odors by the olfactory system, which plays a key role in regulating food intake and elaborating the hedonic value of food, is reciprocally influenced by the metabolic state. Fasting increases olfactory performance, notably by increasing the activity of olfactory bulb (OB) neurons. The glutamatergic synapses between olfactory sensory neurons and mitral cells in the OB glomeruli are regulated by astrocytes, periglomerular neurons, and centrifugal afferents. We compared the expansion of astroglial processes by quantifying GFAP‐labeled areas in fed and fasted rats to see whether OB glomerular astrocytes are involved in the metabolic sensing and adaptation of the olfactory system. Glomerular astroglial spreading was much greater in all OB regions of rats fasted for 17 hr than in controls. Intra‐peritoneal administration of the anorexigenic peptide PYY3‐36 or glucose in 17 hr‐fasted rats respectively decreased their food intake or restored their glycemia, and reversed the fasting‐induced astroglial spreading. Direct application of the orexigenic peptides ghrelin or NPY to OB slices increased astroglial spreading, whereas PYY3‐36 resulted in astroglial retraction, in agreement with the in vivo effects of fasting and satiety on glomerular astrocytes. Thus the morphological plasticity of OB glomerular astrocytes depends on the metabolic state of the rats and is influenced by peptides that regulate food intake. This plasticity may be part of the mechanism by which the olfactory system adapts to food intake.
Improved complexation of paraquats with crown ether‐based pyridyl cryptands
Authors: Price Terry L. , Slebodnick Carla , Gibson Harry W.
Published: December 2017

The commonly used paraquat guest N,N′‐dimethyl‐4,4′‐bipyridinium bis(hexafluorophosphate) (7) was targeted for structural alterations to improve the binding constants with crown ethers and cryptands. The association constant was improved by one order of magnitude (to Ka = 1.00 × 106 mol L−1) with the dibenzo‐30‐crown‐10 pyridyl cryptand host 5 by changing the N‐methyl groups to benzyl and the counterions from PF6 to TFSI, that is, 11. Moreover, through addition of a p‐bromobenzyloxy moiety on the 4‐position of the pyridyl ring of cryptand 18, an association constant of Ka = 5.35 × 106 mol L−1 was achieved with paraquat 11.
Synthesis of a new phosphorylated ethylamine, thereon based phosphonamidates and their application as flame retardants
Authors: Garth Kim , Klinkowski Christoph , Fuhr Olaf , Döring Manfred
Published: December 2017

A new phosphorylated ethylamine salt was synthesized that releases the free amine in situ under water‐free conditions. This storable precursor molecule was used to synthesize a mono‐substituted cyanuric chloride. Further substitutions could not be performed due to the low reactivity of this cyanuric chloride derivative. Also, two novel, bridged phosphonamidates were prepared. Owing to the P‐N synergy, they show enlarged char yields and therefore are promising flame retardants.
A novel pathway activated by somatostatin receptor type 2 (SST2): Inhibition of pituitary tumor cell migration and invasion through cytoskeleton protein recruitment
Authors: Peverelli E. , Giardino E. , Treppiedi D. , Catalano R. , Mangili F. , Locatelli M. , Lania A.G. , Arosio M. , Spada A. , Mantovani G.
Published: December 2017

The pharmacological therapy of GH‐secreting pituitary tumors is based on somatostatin (SS) analogs that reduce GH secretion and cell proliferation by binding mainly SS receptors type 2 (SST2). Antimigratory effects of SS have been demonstrated in different cell models, but no data on pituitary tumors are available. Aims of our study were to evaluate SST2 effects on migration and invasion of human and rat tumoral somatotrophs, and to elucidate the molecular mechanism involved focusing on the role of cofilin and filamin A (FLNA). Our data revealed that SST2 agonist BIM23120 significantly reduced GH3 cells migration (−22% ± 3.6%, p < 0.001) and invasion on collagen IV (−31.3% ± 12.2%, p < 0.01), both these effects being reproduced by octreotide and pasireotide. Similar results were obtained in primary cultured cells from human GH‐secreting tumors. These inhibitory actions were accompanied by a marked increase in RhoA/ROCK‐dependent cofilin phosphorylation (about 2.7‐fold in GH3 and 2.1‐fold in human primary cells). Accordingly, the anti‐invasive effect of the SS analog was mimicked by the overexpression in GH3 cells of the S3D phosphomimetic cofilin mutant, and abolished by both phosphodeficient S3A cofilin and a specific ROCK inhibitor that prevented cofilin phosphorylation. Moreover, FLNA silencing and FLNA dominant‐negative mutants FLNA19‐20 and FLNA21‐24 transfection demonstrated that FLNA plays a scaffold function for SST2‐mediated cofilin phosphorylation. Accordingly, cofilin recruitment to agonist‐activated SST2 was completely lost in FLNA silenced cells. In conclusion, we demonstrated that SST2 inhibits rat and human tumoral somatotrophs migration and invasion through a molecular mechanism that involves FLNA‐dependent cofilin recruitment and phosphorylation.
Preoperative prediction nomogram based on primary tumor miRNAs signature and clinical‐related features for axillary lymph node metastasis in early‐stage invasive breast cancer
Authors: Xie Xinhua , Tan Weige , Chen Bo , Huang Xiaojia , Peng Cheng , Yan Shumei , Yang Lu , Song Cailu , Wang Jianwei , Zheng Wenbo , Tang Hailin , Xie Xiaoming
Published: December 2017

More than half patients who undergo axillary lymph node (ALN) surgery are ALN negative in early‐stage invasive breast cancer (EIBC). Thus, to avoid excessive treatment, we aim to establish and validate a novel nomogram model for the preoperative diagnosis of ALN status in patients with EIBC. In total, 864 patients with EIBC from two independent centers were enrolled in our study. For the discovery set, miRNAs expression profiling with functional roles in ALN metastasis was discovered by microarray analysis and validated by quantitative polymerase chain reaction (PCR). For the training and validation cohorts, we used PCR to quantify miRNAs expression in a model development cohort and assessed miRNAs signature in an internal validation cohort and external independent validation cohort. Multivariable logistic regression analyses were used to establish a nomogram model for the likelihood of ALN metastasis from miRNAs signature and clinical variables. A signature of nine‐miRNA was significantly associated with ALN status. The predictive ability of our nomogram that included miRNAs signature and clinical‐related variables (age, tumor size, tumor location and axillary ultrasound‐reported ALN status) was significantly greater than a model that only considered clinical‐related factors (concordance index: 0.856, 0.796) and also performed well in the two validation cohorts (concordance index: 0.841, 0.747). Our nomogram is a reliable prediction method that can be conveniently used to preoperatively predict ALN status in patients with EIBC. Therefore, after further confirmation in prospective and multicenter clinical trial, omission of axillary surgery may be feasible for some patients with EIBC in the future.
Gold(I)‐Catalyzed C−O/C−C Bond‐Forming Domino Reactions and Their Synthetic Applications
Authors: Bihelovic Filip , Vulovic Bojan , Saicic Radomir N.
Published: December 2017

The advent of gold catalysis has transformed hydroxyalkoxylation of alkynes – once a rudimentary, mercury(II)‐, or silver(I)‐catalyzed process limited to structurally simple substrates – into a sophisticated method that has found application in syntheses of highly complex organic molecules. This transformation can further be combined with carbon‐carbon bond‐forming reactions into domino sequences that allow for a considerable increase of molecular complexity within a single synthetic step. Some recent examples of the development and synthetic applications of these reactions are provided.
Expectations and needs of Ugandan women for improved quality of childbirth care in health facilities: A qualitative study
Authors: Kyaddondo David , Mugerwa Kidza , Byamugisha Josaphat , Oladapo Olufemi T. , Bohren Meghan A.
Published: December 2017

Objective

To describe the experiences, expectations, and needs of urban Ugandan women in relation to good‐quality facility childbirth.

Methods

Women who had given birth in the 12 months prior to the study were purposively sampled and interviewed, or included in focus groups. Thematic analysis was used, and the data were interpreted within the context of an existing quality of care framework.

Results

Forty‐five in‐depth interviews and six focus group discussions were conducted. Respect and dignity, timely communication, competent skilled staff, and availability of medical supplies were central to women's accounts of quality care, or a lack of it. The hope for a live baby motivated women to seek facility‐based childbirth. They expected to encounter competent, respectful, and caring staff with appropriate skills. In some cases, they could only fulfill these expectations through additional personal financial payments to staff, for clinical supplies, or to guarantee that they would be attended by someone with suitable skills.

Conclusion

Long‐term improvement in quality of maternity care in Uganda requires enhancement of the interaction between women and health staff in facilities, and investment in staff and resources to ensure that safe, respectful care is not dependent on willingness and/or capacity to pay.
Design and properties of a novel radiopaque injectable apatitic calcium phosphate cement, suitable for image‐guided implantation
Authors: Le Ferrec Myriam , Mellier Charlotte , Boukhechba Florian , Le Corroller Thomas , Guenoun Daphné , Fayon Franck , Montouillout Valérie , Despas Christelle , Walcarius Alain , Massiot Dominique , Lefèvre François‐Xavier , Robic Caroline , Scimeca Jean‐Claude , Bouler Jean‐Michel , Bujoli Bruno
Published: December 2017

An injectable purely apatitic calcium phosphate cement (CPC) was successfully combined to a water‐soluble radiopaque agent (i.e., Xenetix®), to result in an optimized composition that was found to be as satisfactory as poly(methyl methacrylate) (PMMA) formulations used for vertebroplasty, in terms of radiopacity, texture and injectability. For that purpose, the Xenetix dosage in the cement paste was optimized by injection of the radiopaque CPC in human cadaveric vertebrae under classical PMMA vertebroplasty conditions, performed by interventional radiologists familiar with this surgical procedure. When present in the cement paste up to 70 mg I mL−1, Xenetix did not influence the injectability, cohesion, and setting time of the resulting composite. After hardening of the material, the same observation was made regarding the microstructure, mechanical strength and alpha‐tricalcium phosphate to calcium deficient apatite transformation rate. Upon implantation in bone in a small animal model (rat), the biocompatibility of the Xenetix–containing CPC was evidenced. Moreover, an almost quantitative release of the contrast agent was found to occur rapidly, on the basis of in vitro static and dynamic quantitative studies simulating in vivo implantation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2786–2795, 2018.
Overexpression of Sirt6 is a novel biomarker of malignant human colon carcinoma
Authors: Geng Chang‐hui , Zhang Chun‐ling , Zhang Jing‐yan , Gao Ping , He Miao , Li Yan‐lin
Published: December 2017

Sirt family has been reported playing a significant role in the cancer development, especial its deacetylase activity plays a key function, but whether SIRT6 plays a role in mediating tumor epithelial‐mesenchymal transition (EMT) and metastasis in colon cancer has not been explored. Here, the mass spectrometry and co‐immunoprecipitation assays were utilized to detect that SIRT6 was physically associated with transcription factor snail. Most important, HCT116 cells transfected with SIRT6 shRNA reversed EMT, while increased the expression of TET1, and the HCT116 cells transfected with SIRT6 displayed the contrary tendency. Transwell invasion assay, soft agar assay, as well as colony formation together showed that SIRT6 promoted cell EMT and tumorigenesis in vitro. We also found SIRT6 is a reader of snail. ChIP as well as qChIP suggested H3K9 binding on the promoter of TET1 dependent on SIRT6. SIRT6 promoted EMT process through two different ways, one is as a reader of snail, and other way was the suppression of TET1 transcription. These two ways are all dependent on its H3K9 deacetylase activity. Further, patient samples collected showed that SIRT6 was significantly increased in colon cancer samples, and its higher expression was correlated with poor prognosis, worse overall survivals. Together, our experiments revealed the mechanism for SIRT6 in facilitating tumorigenesis and metastasis of colon cancer cells, suggesting that SIRT6 might be a potential therapeutic target for treating colon cancer.
Retracted: LncRNA XIST functions as a molecular sponge of miR‐194‐5p to regulate MAPK1 expression in hepatocellular carcinoma cell
Authors: Kong Qinglei , Zhang Shaoquan , Liang Caiqian , Zhang Ying , Kong Qingcong , Chen Shuxian , Qin Jie , Jin Yi
Published: December 2017

Increasing evidence highlights the important role of XIST, a long non‐coding RNA (lncRNA), in the regulation of multiple cancers. However, the underlying mechanism of XIST in human hepatocellular carcinoma (HCC) still remains to be explored. Herein, intended to investigate the functional role of XIST in HCC initiation and progression. We first detected that XIST was significantly upregulated in HCC tissues and associated with tumor size and vascular invasion. Gain‐ and loss‐of‐function of XIST further presented that XIST promoted the progression of HCC cells, including proliferation, migration, and invasion. Moreover, silencing of XIST could inhibit tumor growth in vivo. We also found that XIST could target miR‐194‐5p and thus decrease miR‐194‐5p expression. Besides that, restoring XIST could reverse the inhibitory effect of miR‐194‐5p on the proliferation and invasion of HCC cells. We further elucidated such rescue role might through derepressing MAPK1 expression, the target of miR‐194‐5p. In brief, the above results elucidate the important role of XIST in HCC tumorigenesis, suggesting that XIST might be a candidate prognostic biomarker and a novel therapeutic target for treating HCC.
Mir‐29b promotes human aortic valve interstitial cell calcification via inhibiting TGF‐β3 through activation of wnt3/β‐catenin/Smad3 signaling
Authors: Fang Ming , Wang Cheng‐Guang , Zheng Changzhu , Luo Jun , Hou Shiqiang , Liu Kangyong , Li Xinming
Published: December 2017

Herein, we hypothesized that pro‐osteogenic MicroRNAs (miRs) could play functional roles in the calcification of the aortic valve and aimed to explore the functional role of miR‐29b in the osteoblastic differentiation of human aortic valve interstitial cells (hAVICs) and the underlying molecular mechanism. Osteoblastic differentiation of hAVICs isolated from human calcific aortic valve leaflets obtained intraoperatively was induced with an osteogenic medium. Alizarin red S staining was used to evaluate calcium deposition. The protein levels of osteogenic markers and other proteins were evaluated using western blotting and/or immunofluorescence while qRT‐PCR was applied for miR and mRNA determination. Bioinformatics and luciferase reporter assay were used to identify the possible interaction between miR‐29b and TGF‐β3. Calcium deposition and the number of calcification nodules were pointedly and progressively increased in hAVICs during osteogenic differentiation. The levels of osteogenic and calcification markers were equally increased, thus confirming the mineralization of hAVICs. The expression of miR‐29b was significantly increased during osteoblastic differentiation. Furthermore, the osteoblastic differentiation of hAVICs was significantly inhibited by the miR‐29b inhibition. TGF‐β3 was markedly downregulated while Smad3, Runx2, wnt3, and β‐catenin were significantly upregulated during osteogenic induction at both the mRNA and protein levels. These effects were systematically induced by miR‐29b overexpression while the inhibition of miR‐29b showed the inverse trends. Moreover, TGF‐β3 was a direct target of miR‐29b. Inhibition of miR‐29b hinders valvular calcification through the upregulation of the TGF‐β3 via inhibition of wnt/β‐catenin and RUNX2/Smad3 signaling pathways.
Human T‐lymphotropic virus 1 (HTLV‐1) pathogenesis: A systems virology study
Authors: Mozhgani Sayed‐Hamidreza , Zarei‐Ghobadi Mohadeseh , Teymoori‐Rad Majid , Mokhtari‐Azad Talat , Mirzaie Mehdi , Sheikhi Mohsen , Jazayeri Seyed‐Mohammad , Shahbahrami Ramin , Ghourchian Hedayatollah , Jafari Mohieddin , Rezaee Seyed‐Abdolrahim , Norouzi Mehdi
Published: December 2017

The main mechanisms of interaction between Human T‐lymphotropic virus type 1 (HTLV‐1) and its hosts in the manifestation of the related disease including HTLV‐1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and Adult T‐cell leukemia/lymphoma (ATLL) are yet to be determined. It is pivotal to find out the changes in the genes expression toward an asymptomatic or symptomatic states. To this end, the systems virology analysis was performed. Firstly, the differentially expressed genes (DEGs) were taken pairwise among the four sample sets of Normal, Asymptomatic Carriers (ACs), ATLL, and HAM/TSP. Afterwards, the protein‐protein interaction networks were reconstructed utilizing the hub genes. In conclusion, the pathways of cells proliferation and transformation were identified in the ACs state. In addition to immune pathways in ATLL, the inflammation and cancer pathways were discened in both diseases of ATLL and HAM/TSP. The outcomes can specify the genes involved in the pathogenesis and help to design the drugs in the future.
High levels of extracellular ATP lead to chronic inflammatory response in melanoma patients
Authors: Manica Aline , Da Silva Alexsandra Martins , Cardoso Andreia Machado , Moreno Marcelo , Leal Daniela Bittencourt , Dutra Da Silva Anielen , Schetinger Maria Rosa Chitolina , Morsch Vera Maria Melchiors , Bagatini Margarete Dulce
Published: December 2017

Skin cancer represents a serious public health problem and melanoma is considered the most significant due to its high metastasis capacity. Evasion mechanisms are the main characteristic of these tumor cells to escape of immune response. Extracellular nucleotides and nucleosides play an important role in inflammatory and immune responses. In this study, we analyzed the expression and activity of purinergic system enzymes in platelets and lymphocytes, ATP levels quantification, as well the level of pro and anti‐inflammatory interleukins in the serum of 23 patients with surgical melanoma removal (CM group) and 23 control subjects (CT group). Results showed a decrease in ATP, ADP, and AMP hydrolysis and an increase in ATP levels quantification in CM group. The pro‐inflammatory cytokines were elevated in CM group when compared to CT group. These results suggest an inflammatory process, even after surgical removal, due to elevated extracellular ATP levels. Besides, CM group displayed an increase in IL‐10 levels and an increased in ADA activity in platelets and lymphocytes. Once adenosine and IL‐10 are anti‐inflammatory molecules, these results indicate a down‐regulation of immune system front to malignant process. The alteration in nucleotide and nucleoside hydrolysis reinforces the purinergic systems role in this cancer. Therefore, even after surgical removal, the purinergic system can develop a chronic inflammatory micro‐environment that can influence directly on relapse or metastasis.
LncRNA XIST regulates myocardial infarction by targeting miR‐130a‐3p
Authors: Zhou Tao , Qin Guowei , Yang Liehong , Xiang Daokang , Li Suining
Published: December 2017

The study was used to probe long noncoding RNA X‐inactive specific transcript (lncRNA XIST) RNA expression profile and its influence on cell cycle, proliferation, and apoptosis in myocardial cells. We also aimed to explore the possible meditating relationship between XIST, PDE4D, and miR‐130a‐3p. Gene differential analysis was carried out using human lncRNA Microarray V3.0. quantitative real‐time PCR was used to test mRNA expressions of XIST, miR‐130a‐3p, and PDE4D in normal cells and postmyocardial infarction (MI) cells. Western blot was applied to determine the protein expression profile of PED4D. Changes in viability and cell cycle/apoptosis of post‐MI myocardial cells after silencing of XIST or PDE4D were investigated by MTT assay and flow cytometry, respectively. The targeting relationship between miR‐130a‐3p and XIST, PDE4D in myocardial cells were verified by dual luciferase reporter assay. Simulated MI environment was constructed by performing anoxic preconditioning in normal cells to probe the influence of XIST on myocardial cell apoptosis. XIST and PDE4D were overexpressed in post‐MI myocardial cells, whereas miR‐130a‐3p was underexpressed in post‐MI myocardial cells. High‐expressed XIST and PDE4D both promoted myocardial cell apoptosis. High‐expressed XIST also inhibited myocardial cell proliferation. XIST‐downregulated miR‐130a‐3p and PDE4D was a direct target of miR‐130a‐3p. LncRNA XIST promotes MI by targeting miR‐130a‐3p. MI induced by PDE4D can be reversed by miR‐130a‐3p.
M2 muscarinic receptor activation inhibits cell proliferation and migration of rat adipose‐mesenchymal stem cells
Authors: Piovesana Roberta , Melfi Simona , Fiore Mario , Magnaghi Valerio , Tata Ada Maria
Published: December 2017

Mesenchymal stem cells (MSCs), also known as stromal mesenchymal stem cells, are multipotent cells, which can be found in many tissues and organs as bone marrow, adipose tissue and other tissues. In particular MSCs derived from Adipose tissue (ADSCs) are the most frequently used in regenerative medicine because they are easy to source, rapidly expandable in culture and excellent differentiation potential into adipocytes, chondrocytes, and other cell types. Acetylcholine (ACh), the most important neurotransmitter in Central nervous system (CNS) and peripheral nervous system (PNS), plays important roles also in non‐neural tissue, but its functions in MSCs are still not investigated. Although MSCs express muscarinic receptor subtypes, their role is completely unknown. In the present work muscarinic cholinergic effects were characterized in rat ADSCs. Analysis by RT‐PCR demonstrates that ADSCs express M1‐M4 muscarinic receptor subtypes, whereas M2 is one of the most expressed subtype. For this reason, our attention was focused on M2 subtype. By using the selective M2 against Arecaidine Propargyl Ester (APE) we performed cell proliferation and migration assays demonstrating that APE causes cell growth and migration inhibition without affecting cell survival. Our results indicate that ACh via M2 receptors, may contribute to the maintaining of the ADSCs quiescent status. These data are the first evidence that ACh, via muscarinic receptors, might contribute to control ADSCs physiology.
Stem cells rescue cardiomyopathy induced by P. gingivalis‐LPS via miR‐181b
Authors: Chen Tung‐Sheng , Battsengel Sarnai , Kuo Chia‐Hua , Pan Lung‐Fa , Lin Yueh‐Min , Yao Chun‐Hsu , Chen Yueh‐Sheng , Lin Feng‐Huei , Kuo Wei‐Wen , Huang Chih‐Yang
Published: December 2017

Systemic inflammation induced by bacterial infection is one of several causative agents for cardiovascular disorders in patients with periodontal disease. Experimental results indicate that miRNAs play important roles in systemic inflammation induced by endotoxins. Further evidence states that stem cell based therapy shows potential in the treatment of inflammatory responses induced by sepsis. This study investigates if stem cells show protective effects on cardiomyocyte damage induced by porphyromonas gingivalis‐LPS (Pg‐LPS) through regulating miRNAs. H9c2 cardiomyoblasts and neonatal rat cardiomyocytes (NRCMs) were damaged using Pg‐LPS in this study. Pg‐LPS damaged H9c2 or NRCMs were then rescued using adipose‐derived stem cells (ADSC). The experimental results reveal that Pg‐LPS treatment is capable of inducing TLR4/NFκB axis activation, cell death signaling and IGF1R/PI3 K/Akt axis suppression. miR181b was downregulated in Pg‐LPS damaged H9c2/NRCMs. All markers were improved in H9c2/NRCMs cocultured with ADSC. miR181b mimic and inhibitor confirmed that miR181b plays a central role in regulating the cardio protective effect on Pg‐LPS damaged H9c2/NRCMs cocultured with ADSC. miR181b acts as potential therapeutic marker in cardiomyopathy induced by Pg‐LPS. Transplantation of adipose‐derived stem cells show potential in the treatment of cardiomyopathy induced by porphyromonas gingivalis endotoxin via regulation of miR181b.
Syndecans in chronic inflammatory and autoimmune diseases: Pathological insights and therapeutic opportunities
Authors: Agere Solomon A. , Kim Eugene Y. , Akhtar Nahid , Ahmed Salahuddin
Published: December 2017

Syndecans (SDCs) are a family of heparan sulfate proteoglycans (HSPGs) glycoproteins ubiquitously expressed on the cell surfaces and extracellular matrix of all mammalian tissues. There are four mammalian syndecans, SDC‐1 thorough 4, which play a critical role in cell adhesion, migration, proliferation, differentiation, and angiogenesis through independent and growth factor mediated signaling. An altered expression of SDCs is often observed in autoimmune disorders, cancer, HIV infection, and many other pathological conditions. SDCs modulate disease progression by interacting with a diverse array of ligands, receptors, and other proteins, including extracellular matrix, glycoproteins, integrins, morphogens, and various growth factors and chemokines, along with their receptors and kinases. Specifically, SDCs present on cell surface can bind directly to chemokines to enhance their binding to receptors, downstream signaling, and migration. Alternatively, SDCs can be cleaved and shed to mediate negative regulation of chemokine and growth factor signaling pathways and ligand sequestration. Importantly, SDC shedding may be a biomarker of inflammation, especially in chronic inflammatory diseases. While the current therapies for cancer and several autoimmune disorders have revolutionized treatment outcomes, understanding the pathophysiological role of SDCs and the use of HSPG mimetic or antagonists on cytokine signaling networks may uncover potentially novel targeted therapeutic approaches. This review mainly summarizes the current findings on the role of individual SDCs in disease processes, mechanisms through which SDCs mediate their biological functions, and the possibility of targeting SDCs as future potential therapeutic approaches.
MiR‐182‐5p inhibited oxidative stress and apoptosis triggered by oxidized low‐density lipoprotein via targeting toll‐like receptor 4
Authors: Qin Song‐Bai , Peng Da‐Yan , Lu Jing‐Min , Ke Zun‐Ping
Published: December 2017

MicroRNAs (miRNAs) exhibit various roles in multiple biological processes and abnormal expression of miR‐182‐5p has been involved in many diseases. However, the role miR‐182‐5p in Atherosclerosis (AS) remains poorly understood. In our current investigation, an AS model was established by using oxidized low‐density lipoprotein (ox‐LDL) in RAW264.7 cells. miR‐182‐5p was markedly decreased in AS model dose‐dependently and time‐dependently. Additionally, CD36, oil‐red staining levels, TC, and TG were inhibited by miR‐182‐5p mimics, meanwhile ROS levels, MDA, and cell apoptosis were also restrained with an enhancement of SOD activity. Consistently, opposite results were exhibited when miR‐182‐5p inhibitors were transfected into RAW264.7 cells. It is well known that toll‐like receptor 4 (TLR4) is responsible for many inflammation diseases. By using bioinformatics analysis, TLR4 was indicated as a potential target of miR‐182‐5p. We observed TLR4 was activated in AS models and miR‐182‐5p could repress AS progression by targeting TLR4 in vitro. In conclusion, we uncovered that miR‐182‐5p played significant roles in AS through inhibiting oxidative stress and apoptosis via inactivating TLR4 expression.
Cudratricusxanthone A attenuates sepsis‐induced liver injury via SIRT1 signaling
Authors: Lee Yuri , Jeong Gil‐Saeng , Kim Kyung‐Min , Lee Wonhwa , Bae Jong‐Sup
Published: December 2017

Cudratricusxanthone A (CTXA), a natural bioactive compound extracted from the roots of Cudraniatricuspidata Bureau, is known to possess antithrombotic, antiproliferative, and antiinflammatory activities. It remains unclear that CTXA can improve hepatoprotective activity in vivo. The objective of this study was to investigate the effect of CTXA on lipopolysaccharide (LPS)‐induced liver failure in mice, and to elucidate its underlying molecular mechanisms. Liver failure was induced by LPS (15 mg/kg, i.p.) in mice, and 12 hr later, they were treated intravenously with CTXA. Administration of LPS significantly increased mortality, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and serum inflammatory cytokines. CTXA treatment effectively countered these effects of LPS. Further, LPS treatment markedly increased the expression of myeloperoxidase, phosphorylation of p38, extracellular signal‐regulated kinase (ERK), and c‐Jun N‐terminal kinase (JNK), and expressions of nuclear proteins, such as nuclear factor (NF)‐κB and phosphorylated c‐Jun. Additionally, LPS increased the serum levels of tumor necrosis factor (TNF)‐α and interleukin (IL)‐6. All these effects of LPS were attenuated by CTXA. Moreover, CTXA increased the expression of sirtuin‐1 (SIRT1) and reduced the expression of acetylated forkhead box O1 box O1 (Ac‐FoxO1), acetylated Ac‐p53, and acetylated nuclear factor‐kappa beta (Ac‐NF‐κB). In conclusion, CTXA alleviates LPS‐induced liver injury by reducing inflammatory responses and the potential mechanism is associated with SIRT1 signaling activation and finally could be used to treat liver diseases.
Study of microRNAs targeted Dvl2 on the osteoblasts differentiation of rat BMSCs in hyperlipidemia environment
Authors: Huang Xin , Wang Zhifeng , Li Duoduo , Huang Zhengfei , Dong Xiaofei , Li Chuanhua , Lan Jing
Published: December 2017

Dishevelled 2 (Dvl‐2), a key mediator of the wnt/β‐catenin signaling pathway, plays critical roles in osteoblasts differentiation in hyperlipidemia environment. In our previous study, we observed a strong correlation between increased dvl2 expression and decreased new bone formation around implants in a rat hyperlipidemia implant surgery model. However, transcriptional regulation of Dvl2 by microRNAs in this process remains unknown. In the current study, we searched in online database and identified four significantly up‐regulated miRNAs, miR‐21‐5p, miR‐29c‐3p, miR‐138‐5p, and miR‐351‐5p that could potentially regulate Dvl2. Using Western blot and dual‐luciferase assays, we confirmed that miR29c‐3p suppresses Dvl2 expression by binding to its 3′‐UTR. Our results suggest a novel transcriptional regulation mechanism of Dvl2 by miR‐29c‐3p in osteoblasts differentiation of BMSCs.
Analysis of secreted peptidome from omental adipose tissue in polycystic ovarian syndrome patients
Authors: Jia Genmei , Tao Hongjiang , Xue Yunping , Xu Sujuan , Xue Kai , Zhu Qiaoying , Chen Xiaoyan , Liu Xiaoguang , Xu Siliang , Li Qian , Xu Pengfei
Published: December 2017

Polycystic ovarian syndrome (PCOS) is a common endocrinopathy associated with increased risk of metabolic disorders. Prevalence of adiposity and obesity is greater in women suffering from PCOS. Moreover, adipose tissue dysfunction has been demonstrated in PCOS patients, particularly in abdominal adipose tissue. This dysfunction likely aggravates the metabolic and reproductive abnormalities. We used liquid chromatography‐mass spectrometry to compare the peptides secreted from PCOS and non‐PCOS abdominal adipose tissue. We detected 298 upregulated peptides and 31 downregulated peptides (absolute fold change ≥ 2 and p < 0.05). Twenty‐nine peptides were only detected in the PCOS group, while 18 were only detected in the control group. In addition, we demonstrate that these cleavage products are not degradation products of the proteasome based on previous studies reported. Gene Ontology enrichment and pathway analysis were performed to study differentially secreted peptides through their precursor proteins. We identified 12 peptides from 10 precursor proteins associated with PCOS, and 6 peptide sequences were located in the functional domains of their corresponding precursor proteins. These results provide a deeper understanding of adipose tissue‐derived peptides in PCOS for future functional studies.
Diagnostic delay for imported malaria: A case of Plasmodium falciparum malaria misdiagnosed as common cold
Authors: Hase Ryota
Published: December 2017

A 37‐year‐old Japanese man experienced fever and headache 8 days after returning to Japan following a 6‐month stay in Nigeria. He visited two clinics but was sent home from each with a diagnosis of common cold. He was eventually brought to the emergency department with an altered mental status. Severe P. falciparum malaria was confirmed; his initial parasitemia index was 5.4%. He recovered fully with antimalarial treatment. This case suggests that primary care physicians should obtain recent travel history and consider malaria for any febrile patient who has returned from a malaria‐endemic area.
Every graph occurs as an induced subgraph of some hypohamiltonian graph
Authors: Zamfirescu Carol T. , Zamfirescu Tudor I.
Published: December 2017

We prove the titular statement. This settles a problem of Chvátal from 1973 and encompasses earlier results of Thomassen, who showed it for K3, and Collier and Schmeichel, who proved it for bipartite graphs. We also show that for every outerplanar graph there exists a planar hypohamiltonian graph containing it as an induced subgraph.
Global and regional evaluation of a global model simulated AODs with AERONET and MODIS observations
Authors: Sheel Varun , Guleria Raj P. , Ramachandran S.
Published: December 2017

Aerosol optical properties vary widely globally due to their short residence time and the large variability in their composition and size resulting from varying sources. In this study, we make use of the three‐dimensional global atmospheric chemistry transport model MOZART (Model for OZone And Related chemical Tracers), to simulate Aerosol Optical Depths (AODs) and compare with observations from MODIS (Moderate Resolution Imaging Spectroradiometer, level‐3) on board the Terra satellite and AERONET (AErosol RObotic NETwork level‐2), at regional and global scale for the period 2000–2007. The AOD values at a reference wavelength 550 nm are reported for all the data sets. Model and observations show intense aerosol burden over the parts of the world where developing countries are located. On a regional scale, varying features are noted for different regions depending upon topography, regional emissions and weather conditions. MOZART captures the general features observed in AERONET and MODIS fairly well; however, in biomass burning dominated regions (Central South America, South Africa, and North Australia) it underestimates the observed AOD. In industrial regions (North Europe and Mediterranean) MOZART overestimates the observations and over dust dominant regions (Saharan Africa, Middle East, and East Asia), the model AODs are comparable to AERONET and MODIS observations. In general, MOZART simulated AOD show similar seasonal and regional variability as observed in AERONET and MODIS. Our results are similar to the most commonly used models, i.e. GOCART (the GOddard Chemistry, Aerosol, Radiation, and Transport) and GEOS‐4 (Goddard Earth Observing System‐version 4).
Unique relationship between tropical rainfall and SST to the north of the Mozambique Channel in boreal winter
Authors: Koseki Shunya , Bhatt Bhuwan Chandra
Published: December 2017

In this study, we investigate a possible mechanism for the dichotomy in climatology of marine rainfall and sea surface temperature (SST) over a part of the Southwest Indian Ocean (SWIO) during boreal winter (January and February) with state‐of‐the‐art satellite and reanalysis data sets. Rainfall to the north of the Mozambique Channel, bounded 10°–5°S and 40°–50°E, is found to be quite feeble despite being in the warm SST regime of up to 29–29.5 °C. The rainfall intensity is rather found to be highly associated with the atmospheric surface divergence. The vigorous rainfall is associated with the more convergence over the Intertropical Convergence Zone (ITCZ), while the weak rainfall is linked with the divergence to the north of the Mozambique Channel. The surface divergent flow to the north of the Mozambique Channel is associated with a deep southward penetration of the northerly Indian Winter Monsoon (IWM). Corresponding to the surface divergent field, a relatively high sea level pressure (SLP) compared to the SLP in the ITCZ, weak subsidence, and low‐level stratiform clouds are formed to the north of the Mozambique Channel, despite the warm, tropical SST. These atmospheric conditions are most likely conductive to the inhibition of cumulus convection over the region and the unique relationship between rainfall and SST seems peculiar. Our analysis also shows that the rare occurrence of tropical cyclones over the area is attributed to a high‐pressure surge and the associated positive surface vorticity (anti‐cyclonic). This study suggests that the area to the north of the Mozambique Channel is dynamically interesting for climatological studies.
Storm wave clustering around New Zealand and its connection to climatic patterns
Authors: Godoi Victor A. , Bryan Karin R. , Gorman Richard M.
Published: December 2017

Clusters of storm waves contribute disproportionately to coastal erosion hazards because the coastline has insufficient time to recover between events. Here, the change in occurrence of clustered storms and its association with atmospheric oscillation modes were investigated in New Zealand waters using 44 years (1958–2001) of wave hindcast data. First, long‐term averages of cluster parameters (number of storms within the cluster, potential for coastal erosion, and cluster duration) were assessed. Then, the relationships between clustering and the El Niño‐Southern Oscillation (ENSO), Indian Ocean Dipole (IOD), Zonal Wavenumber‐3 Pattern (ZW3), Pacific Decadal Oscillation (PDO), and Southern Annular Mode (SAM) were explored through correlation analysis over several timescales. Clusters were more frequently observed to the northeast of New Zealand and on the central eastern coast of the South Island. The most vulnerable regions to cluster‐induced coastal erosion were southern New Zealand and the northwestern coast, which resulted from steady southwesterly swells, although clusters with the longest duration occurred on the east coast of the South Island. Trends suggest that clusters have incorporated more storms, have become more hazardous, and have increased in duration, particularly along the South Island coastline. Although these trends may be sensitive to the reanalysed wind fields used to force the wave hindcast, they reflect trends in the ENSO, PDO, and SAM. Stronger southwesterly winds during El Niño (negative ENSO) and El Niño‐like conditions (positive IOD/PDO) generated more clustered storms mainly on the southwestern coast of New Zealand, whereas increases in clustering were observed on the north coast during La Niña and La Niña‐like conditions (stronger northeasterly winds). Higher occurrence of clustering was also evident on the west coast during the strong atmospheric zonal flow associated with negative ZW3. Lastly, strengthened westerlies related to positive SAM led to increased clustering primarily to the south of New Zealand.
Creative self‐efficacy as mediator between creative mindsets and creative problem‐solving
Authors: Royston Ryan , Reiter‐Palmon Roni
Published: December 2017

An emerging area of research is how one's mindset regarding the fixedness and malleability of creative ability relates to creative performance. Malleable creative mindsets tend to be positively related to creativity while fixed mindsets often show a negative association. Similarly, creative self‐efficacy, or one's beliefs that they have the capacity to be creative, is also related to creative performance and creative mindsets. While previous studies tested the direct relationship between mindsets and creativity, this study tested creative self‐efficacy in this relationship. A total of 152 students from a Midwestern university participated in the study. They were provided with measures of creative self‐efficacy, creative mindsets, and creative problem‐solving. Solutions were assessed in terms of quality and originality. Results indicated that both malleable creative mindsets and creative self‐efficacy were positively related to solution quality and originality while fixed creative mindsets were negatively related. Mediation analysis using Preacher and Hayes' (2004) bootstrapping macro showed that creative self‐efficacy mediated the relationship between malleable mindsets and quality and originality as well as the relationship between fixed mindsets and quality and originality. This research advances the study of creativity by demonstrating that creative self‐efficacy is an important mechanism through which creative mindsets relate to creative performance.
Clinical features and survival of gastric cancer patients with DNA mismatch repair deficiency
Authors: Ikoma Naruhiko , Cloyd Jordan , Badgwell Brian D. , Agnes Annamaria , Rodriguez‐Bigas Miguel , Ajani Jaffer A. , You Y. Nancy
Published: December 2017

Patients with germline DNA mismatch repair deficiency (dMMR) have an increased risk of gastric cancer. From our institutional database, we identified 12 patients with germline dMMR gastric cancer. Ten patients (83%) underwent surgical resection, with a 5‐year overall survival rate of 88%. None of the three patients who received preoperative therapy and five patients with recurrent or metastatic disease experienced a significant response to 5‐fluorouracil–based chemotherapy.
Concomitant organ resection does not improve outcomes in primary retroperitoneal well‐differentiated liposarcoma: A retrospective cohort study at a major sarcoma center
Authors: Ikoma Naruhiko , Roland Christina L. , Torres Keila E. , Chiang Yi‐Ju , Wang Wei‐Lien , Somaiah Neeta , Mann Gary N. , Hunt Kelly K. , Cormier Janice N. , Feig Barry W.
Published: December 2017

Background

We investigated whether concomitant organ removal as part of the primary resection of RP WDLPS confers an outcome advantage in patients treated at a major sarcoma center.

Methods

The departmental sarcoma database was reviewed to identify patients with RP WDLPS who underwent initial surgical resection for primary disease at MD Anderson Cancer Center during the study period 1995‐2011. We retrospectively reviewed medical records and examined associations between clinicopathologic variables and overall survival (OS) as well as disease‐free survival (DFS).

Results

Among 83 patients included in this study, 76 patients (92%) underwent complete resection (R0/R1). Concomitant organ resections were performed in 38 patients (46%). Invasion of the resected organ/s was seen in six patients (7%). Estimated OS was 11.3 years (5‐year OS, 86%), and DFS was 5.4 years (5‐year DFS, 51%). By multivariate analysis, concomitant organ resection was not associated with improved OS (P = 0.428) or DFS (P = 0.946), and lack of organ resection was associated with a lower risk of postoperative complications (P = 0.01).

Conclusions

Concomitant organ resection was not associated with a survival benefit in RP WDLPS in this study. In patients with primary RP WDLPS, we recommend selective resection of contiguous organs only if there is clinical suspicion of invasion.
Cryogenic modulation fast GC × GC–MS using a 10 m microbore column combination: Concept, method optimization, and application
Authors: Giocastro Barbara , Piparo Marco , Tranchida Peter Q. , Mondello Luigi
Published: December 2017

The present research is based on the concept of using a 10 m × 0.1 mm id column for cryogenic‐modulation fast comprehensive two‐dimensional gas chromatography with quadrupole mass spectrometry. Specifically, an 8.9 m × 0.1 mm id low‐polarity column was used as the first dimension, and a 1.1 m × 0.1 mm id medium‐polarity column was used as the second dimension. The main scope of the investigation was to develop a high peak‐capacity method, with an analysis time of approximately 10 min. Various aspects related to method optimization are discussed, as well as separation parameters such as peak capacity (in each dimension, and as a total value), first‐dimension sample capacity, peak widths, modulation ratio, sensitivity enhancement, and number of spectra per peak. The fast approach was evaluated in applications involving a mixture of cosmetic allergens and a sample of perfume. The approach proposed enables high‐resolution separations in a short time (across the C8–C23 alkane range), as well as a considerable reduction of the consumption of gases for modulation cooling and heating.