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Jihwan Myung, Christoph Schmal, Sungho Hong, Yoshiaki Tsukizawa, Pia Rose, Yong Zhang, Michael J Holtzman, Erik De Schutter, Hanspeter Herzel, Grigory Bordyugov, Toru Takumi
Mammalian circadian clocks have a hierarchical organization, governed by the suprachiasmatic nucleus (SCN) in the hypothalamus. The brain itself contains multiple loci that maintain autonomous circadian rhythmicity, but the contribution of the non-SCN clocks to this hierarchy remains unclear. We examine circadian oscillations of clock gene expression in various brain loci and discovered that in mouse, robust, higher amplitude, relatively faster oscillations occur in the choroid plexus (CP) compared to the SCN...
March 14, 2018: Nature Communications
Clive M Michelo, Bram van Cranenbroek, Peran Touw, Frans H J Claas, Arnold van der Meer, Irma Joosten
Background: Antibody-mediated rejection in solid organ transplantation is an important immunological barrier to successful long-term graft survival. Next to complement activation, natural killer (NK) cells have been implicated in the process. Human cytomegalovirus (CMV), independently associated with decreased graft survival, has a strong imprint on the immune response. Here, we assessed the effect of CMV status on alloreactive NK cell reactivity. Methods: We compared antibody-mediated NK cell cytolytic activity (CD107a expression) and IFNγ production between healthy CMV-seropositive (n = 8) and CMV-seronegative (n = 11) individuals, in cocultures of NK cells with anti-HLA class I or rituximab (control) antibody-coated Raji cells...
December 2017: Transplantation Direct
Fawaz Abomaray, Sebastian Gidlöf, Bartosz Bezubik, Mikael Engman, Cecilia Götherström
Endometriosis is an inflammatory disease marked by ectopic growth of endometrial cells. Mesenchymal stromal cells (MSC) have immunosuppressive properties that have been suggested as a treatment for inflammatory diseases. Therefore, the aim herein was to examine effects of allogeneic MSC on endometriosis-derived cells in vitro as a potential therapy for endometriosis. MSC from allogeneic adipose tissue (Ad-MSC) and stromal cells from endometrium (ESCendo ) and endometriotic ovarian cysts (ESCcyst ) from women with endometriosis were isolated...
2018: Stem Cells International
Fei Xiao, Stanley Wang, Rina Barouch-Bentov, Gregory Neveu, Szuyuan Pu, Melanie Beer, Stanford Schor, Sathish Kumar, Vlad Nicolaescu, Brett D Lindenbach, Glenn Randall, Shirit Einav
Hepatitis C virus (HCV) spreads via secreted cell-free particles or direct cell-to-cell transmission. Yet, virus-host determinants governing differential intracellular trafficking of cell-free- and cell-to-cell-transmitted virus remain unknown. The host adaptor proteins (APs) AP-1A, AP-1B, and AP-4 traffic in post-Golgi compartments, and the latter two are implicated in basolateral sorting. We reported that AP-1A mediates HCV trafficking during release, whereas the endocytic adaptor AP-2 mediates entry and assembly...
March 13, 2018: MBio
Jesse D Noar, Jose M Bruno-Bárcena
Azotobacter vinelandii has been studied for over 100 years since its discovery as an aerobic nitrogen-fixing organism. This species has proved useful for the study of many different biological systems, including enzyme kinetics and the genetic code. It has been especially useful in working out the structures and mechanisms of different nitrogenase enzymes, how they can function in oxic environments and the interactions of nitrogen fixation with other aspects of metabolism. Interest in studying A. vinelandii has waned in recent decades, but this bacterium still possesses great potential for new discoveries in many fields and commercial applications...
March 13, 2018: Microbiology
Huan Yi, Bingbing Xie, Ben Liu, Xuan Wang, Li Xu, Jia Liu, Min Li, Xiufeng Zhong, Fuhua Peng
Induced pluripotent stem cells (iPSCs) have provided new opportunities for motor neuron disease (MND) modeling, drug screening, and cellular therapeutic development. Among the various types of iPSCs, urine-derived iPSCs have become a promising source of stem cells because they can be safely and noninvasively isolated and easily reprogrammed. Here, for the first time, we differentiated urine-derived iPSCs (urine-iPSCs) into motor neurons (MNs) and compared the capacity of urine-iPSCs and cord-blood-derived iPSCs (B-iPSCs) to differentiate into MNs...
2018: Stem Cells International
Annalucia Carbone, Roberto Zefferino, Elisa Beccia, Valeria Casavola, Stefano Castellani, Sante Di Gioia, Valentina Giannone, Manuela Seia, Antonella Angiolillo, Carla Colombo, Maria Favia, Massimo Conese
We previously found that human amniotic mesenchymal stem cells (hAMSCs) in coculture with CF immortalised airway epithelial cells (CFBE41o- line, CFBE) on Transwell® filters acquired an epithelial phenotype and led to the expression of a mature and functional CFTR protein. In order to explore the role of gap junction- (GJ-) mediated intercellular communication (GJIC) in this rescue, cocultures (hAMSC : CFBE, 1 : 5 ratio) were studied for the formation of GJIC, before and after silencing connexin 43 (Cx43), a major component of GJs...
2018: Stem Cells International
Shaoyong Zhuang, Xiangwei Hua, Kang He, Tao Zhou, Jiang Zhang, Haoyu Wu, Xiong Ma, Qiang Xia, Jianjun Zhang
The contribution of glycogen synthase kinase-3β (GSK-3β) to cholestatic liver disease (CLD) remains unknown. We investigated the role and mechanism of GSK-3β in vivo in liver tissues of patients with CLD and the bile duct ligation (BDL) mouse model and in vitro using a hepatic progenitor cell (HPC) and hepatic stellate cell (HSC) coculture system. In liver tissues of patients with CLD, expression of the inactive form of GSK-3β, phospho-GSK-3β(Ser9), was increased in HPCs. GSK-3β inhibition by SB216763 treatment aggravated liver fibrosis and elevated the expression of osteopontin (OPN) in the BDL mouse model...
March 12, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Carlos Zamora, Elisabet Canto, Juan C Nieto, Ester Garcia-Planella, Jordi Gordillo, Mª Angels Ortiz, Xavier Suarez-Calvet, Lidia Perea, Germà Julia, Candido Juarez, Silvia Vidal
Background: Circulating monocytes from active ulcerative colitis (UC) patients produced high levels of tumor necrosis factor-alpha(TNFα) and interleukin(IL)-6 after Toll-like receptors (TLR) stimulation. Since platelets (PLT) can bind to leukocytes, thereby decreasing inflammatory cytokine production, UC patients may exhibit different levels of monocyte-platelet complexes depending on disease activity. Methods: We compared among healthy donors, active (onset flare and relapse), and inactive UC patients the presence of circulating monocyte-platelet complexes (CD14+PLT+) and membrane CD162 expression by flow cytometry...
February 23, 2018: Inflammatory Bowel Diseases
Penny E Morton, Maddy Parsons
Migration of leukocytes through epithelial monolayers represents an essential step in the generation of an inflammatory response and is often seen in inflammatory conditions such as Crohn's disease (Matthews et al., Toxicol Pathol 42:91-98, 2014) and asthma (Lambrecht and Hammad, Nat Med 18:684-692, 2012). Transepithelial migration involves adhesion to the basal surface of the epithelium before migration through the epithelial cell layer to the apical surface. Analyzing this process can present a technical challenge due to complications of using a coculture model and trying to recapitulate an intact monolayer...
2018: Methods in Molecular Biology
Franck Da-Silva, Xavier Boulenc, Hélène Vermet, Pauline Compigne, Sabine Gerbal-Chaloin, Martine Daujat-Chavanieu, Sylvie Klieber, Patrick Poulin
The objective was to compare, with the same dataset, the predictive performance of three in vitro assays of hepatic clearance (CL), namely, micropatterned cocultures (MPCC) (also referring to HepatoPac® ) and suspension as well as monolayer hepatocytes to define which assay is the most accurate. Furthermore, existing in vitro-to-in vivo extrapolation (IVIVE) methods were challenged to verify which method is the most predictive (i.e., direct scaling method without binding correction, conventional method based either on the unbound fraction in plasma (fup ) according to the free drug hypothesis, or based on an fup value adjusted for the albumin (ALB)-facilitated hepatic uptake phenomenon)...
March 7, 2018: Journal of Pharmaceutical Sciences
Ruili Yang, Tingting Yu, Dawei Liu, Songtao Shi, Yanheng Zhou
BACKGROUND: Mesenchymal stem cells derived from gingiva (GMSCs) display profound immunomodulation properties in addition to self-renewal and multilineage differentiation capacities. Hydrogen sulfide (H2 S) is not only an environmental pollutant, but also is an important biological gas transmitter in health and disease. METHODS: We used an in-vitro coculture system and a mouse colitis model to compare the immunomodulatory effects between control and H2 S-deficient GMSCs...
March 9, 2018: Stem Cell Research & Therapy
Chao Ren, Peiyuan Yin, Neng Ren, Zhe Wang, Jiahui Wang, Caiyi Zhang, Wei Ge, Deqin Geng, Xiaotong Wang
Recent studies have suggested that the regulation of endogenous neural stem cells (NSCs) or transplanting of exogenous nerve cells are the newest and most promising methods for the treatment of dementia and other neurological diseases. The special location and limited number of endogenous NSCs, however, restrict their clinical application. The success in directional differentiation of exogenous stem cells from other tissue sources into neural cells has provided a novel source for NSCs. Study on the relative mechanisms is still at the preliminary stage...
March 9, 2018: Stem Cell Research & Therapy
Ryota Kurogi, Akira Nakamizo, Satoshi O Suzuki, Masahiro Mizoguchi, Koji Yoshimoto, Toshiyuki Amano, Takeo Amemiya, So Takagishi, Koji Iihara
OBJECTIVE Human bone marrow-derived mesenchymal stem cells (hMSCs) show tropism for brain tumors and may be a useful vehicle for drug or gene delivery to malignant gliomas. Recently, some microRNAs (miRNAs) have been shown to suppress the invasiveness of malignant gliomas. METHODS To test their potential to become vehicles for the delivery of miRNA to malignant gliomas, hMSCs were engineered so that hMSC secretion of miRNAs that inhibit glioma cell invasion was enabled without altering the hMSC tropism for glioma cells...
March 9, 2018: Journal of Neurosurgery
Dale George, Paige Ahrens, Stephen Lambert
Satellite glial cells (SGCs) are glial cells in the peripheral nervous system that form sheaths around the neuronal cell body. This unique arrangement of SGCs allows it to exert a highly regulated control over the neuronal microenvironment. Not much is known about the origin of SGCs. In this study, we examine the development of SGCs. We show that rat SGCs develop postnatally and these cells express a number of markers associated with Schwann cell precursors, in particular cadherin-19 (CDH19) even in adult DRGs...
March 9, 2018: Glia
Yasuyuki Negishi, Tomoko Ichikawa, Toshiyuki Takeshita, Hidemi Takahashi
Unexpected fetal loss is one of the common complications of pregnancy; however, the pathogenesis of many miscarriages, particularly those not associated with infections, is unknown. We previously found that activated DEC-205+ dendritic cells (DCs) and NK1.1+ invariant natural killer T (iNKT) cells are recruited into the myometrium of mice when miscarriage is induced by the intraperitoneal administration of α-galactosylceramide (α-GalCer). Here we demonstrate that the adoptive transfer of DEC-205+ bone marrow-derived DCs cocultured with α-GalCer (DEC-205+ BMDCs-c/w-α-GalCer) directly induced marked fetal loss by syngeneic pregnant C57BL/6 (B6) mice and allogeneic mice (B6 (♀) × BALB/c (♂)), which was accompanied by the accumulation of activated iNKT cells in the myometrium...
March 9, 2018: European Journal of Immunology
Fang Gong, Hua-Yan Zhu, Jie Zhu, Qiao-Jing Dong, Xuan Huang, Dong-Jin Jiang
The pathogenesis of allergic asthma is primarily characterized by abnormality in immunoglobin(Ig)E pathway, suggesting a possible role for follicular helper T cells (Tfh) in the genesis of excessive IgE accumulation. The blood chemokine (C-X-C motif) receptor 5 (CXCR)5+ CD4+ T cells, known as "circulating" Tfh, share common functional characteristics with Tfh cells from germinal centers. The aim of this study was to determine the phenotypes and functions of circulating CXCR5+ CD4+ T cells in allergic asthmatics...
March 5, 2018: Immunology Letters
P E Mandelare, D A Adpressa, E N Kaweesa, L N Zakharov, S Loesgen
The genetically encoded, small-molecule chemical diversity of filamentous fungi is still largely unexplored and represents an attractive source for the discovery of new compounds. Here we report the production of new chlorinated bianthrones from coculture of two different developmental stages, or morphs, of a marine alga-derived Aspergillus alliaceus (teleomorph: Petromyces alliaceus) strain. The vegetative stage (asexual morph) can be separated from the morph that switched to sexual development (sclerotial morph); both produce distinct secondary metabolite patterns...
March 8, 2018: Journal of Natural Products
Sudeep Chenna Narendra, Jaya Prakash Chalise, Sophie Biggs, Ulrich Kalinke, Mattias Magnusson
Objective: CD4+ FoxP3+ CD25+ regulatory T-cells (Tregs ) are important for preventing tissue destruction. Here, we investigate the role of Tregs for protection against experimental arthritis by IFN-α. Methods: Arthritis was triggered by intra-articular injection of methylated bovine serum albumin (mBSA) in wild-type mice, Foxp3DTReGFP+/- mice [allowing selective depletion of Tregs by diphtheria toxin (DT)] and CD4-Cre+/- IFNA1R flox/flox mice (devoid of IFNAR signaling in T-cells) earlier immunized with mBSA, with or without treatment with IFN-α or the indoleamine 2,3-dioxygenase (IDO)-metabolite kynurenine...
2018: Frontiers in Immunology
Chengfang Shangguan, Guifang Gan, Jieying Zhang, Jinliang Wu, Ying Miao, Miao Zhang, Biao Li, Jun Mi
Purpose: Elevated glucose uptake is a hallmark of cancer. Fluorodeoxyglucose (FDG) uptake was believed to indicate the aggressiveness of tumors and the standardized uptake value (SUV) is a well-known measurement for FDG uptake in positron emission tomography-computed tomography (PET/CT). However, the SUV is variable due to the heterogeneity of tumors. Methods: 126 patients with colorectal cancer underwent18 F-FDG PET/CT scanning before surgery between Jan 2011 and April 2016. Cancer-associated fibroblast (CAF) densities were calculated with the inForm Advanced image analysis software and were comparatively analyzed between patients with high and low maximum SUV (SUVmax-high and SUVmax-low)...
2018: Theranostics
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