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Hui Zhao, Flora S Kalish, Ronald J Wong, David K Stevenson
PROBLEM: Uterine and placental macrophages play critical roles in maintaining a normal pregnancy. The majority of these macrophages are believed to be alternatively activated macrophages (M2). METHOD OF STUDY: Mouse bone marrow cells were differentiated into macrophages and polarized to M2 in vitro by treatment with IL-4 [M2a] or IL-10 [M2c] and M1 with LPS/IFN-γ as controls. Macrophage subtypes were confirmed by surface markers and characterized by gene expression profiles...
June 22, 2018: American Journal of Reproductive Immunology: AJRI
Song Zhou, Yong-Guang Liu, Ya Zhang, Jian-Min Hu, Ding Liu, Hua Chen, Min Li, Ying Guo, Li-Pei Fan, Liu-Yang Li, Ming Zhao
An increasing number of experiments and clinical trials have demonstrated the safety, feasibility, and efficacy of mesenchymal stem cells (MSCs)-based therapies for the treatment of various diseases. The main drawbacks of MSC therapy are the lack of specific homing after systemic infusion and early death of injected cells because of the injury micro-environment. We pretreated bone mesenchymal stem cells (BMSCs) with erythropoietin (EPO) to investigate their positive effect on cyclosporine A (CsA)-induced nephrotoxicity...
June 22, 2018: Journal of Cellular Biochemistry
Ayman S Samman-Tahhan, Muhammad Hammadah, Heval M Kelli, Jeong Hwan Kim, Pratik B Sandesara, Ayman Alkhoder, Belal Kaseer, Mohamad M Gafeer, Matthew L Topel, Salim S Hayek, Wesley T O'Neal, Malik Obideen, Yi-An Ko, Chang Liu, Iraj Hesaroieh, Ernestine A Mahar, Viola Vaccarino, Edmund K Waller, Arshed A Quyyumi
<u>Rationale:</u> Blacks compared to Whites have a greater risk of adverse cardiovascular outcomes. Impaired regenerative capacity, measured as lower levels of circulating progenitor cells (CPCs), is a novel determinant of adverse outcomes, however, little is known about racial differences in CPCs. <u>Objective:</u> To investigate the number of CPCs, PC-mobilizing factors, PC mobilization during acute myocardial infarction (AMI) and the predictive value of CPC counts in Blacks compared with Whites...
June 21, 2018: Circulation Research
Nancy Adriana Espinoza-Sánchez, Jennifer Enciso, Rosana Pelayo, Ezequiel M Fuentes-Pananá
Breast cancer is a complex disease exhibiting extensive inter- and intra-tumor heterogeneity. Inflammation is a well-known driver of cancer progression, often attributed to immune cells infiltrating the tumor stroma. However, tumor cells themselves are capable to secrete a variety of inflammatory molecules, of which we understand very little about their role in intra-clonal communication. We recently reported the capacity of triple negative cell lines to induce a cancer stem cell (CSC)-like phenotype and invasion properties into luminal cells, a mechanism mediated by pro-inflammatory cytokines that up-regulated the CXCL12/CXCR4/CXCR7 chemokine signaling axis...
June 1, 2018: Oncotarget
Amanda B Macedo, Rachel S Resop, Laura Jean Martins, Matthew A Szaniawski, Eric S Sorensen, Adam M Spivak, Douglas F Nixon, R Brad Jones, Vicente Planelles, Alberto Bosque
Primary cell models of HIV latency have become tools to both understand the mechanisms involved in the establishment of latency as well as to test pre-clinical strategies towards an HIV-1 cure. These models rely on the infection of CD4 T cells from healthy donors. As such, these models provide an opportunity to explore the role of biological sex, age and HIV status on the establishment and reactivation of latent HIV in vitro. We have used an established primary cell model of latency based on the generation of latently infected central memory CD4 T cells with the CXCR4-strain HIV-1NL4-3 to address whether these variables influence: i) HIV-1NL4-3 replication, ii) establishment of latency, and iii) latency reversal in CD4 T cells...
June 21, 2018: AIDS Research and Human Retroviruses
Alda Losi Guembarovski, Roberta Losi Guembarovski, Bruna Karina Banin Hirata, Glauco Akelinghton Freire Vitiello, Karen Mayumi Suzuki, Mayara Tiemi Enokida, Maria Angelica Ehara Watanabe, Edna Maria Vissoci Reiche
CXCL12/CXCR4 signaling has been implicated in breast carcinogenesis, and genetic polymorphisms in these molecules have been associated with different types of cancer. The present study analyzed genetic polymorphisms in CXCL12 (rs1801157, G > A) and CXCR4 (rs2228014, C > T) and CXCR4 immunostaining in tumor tissues from patients with triple negative breast cancer (TNBC) aiming to evaluate their possible role in its' susceptibility and prognosis. Genetic polymorphisms were analyzed in 59 TNBC patients and 150 control women; age-adjusted logistic regression showed no association when variants were considered in isolation; however, a statistically significant interaction was noted for heterozygosis for both allelic variants increasing the odds for TNBC (CXCL12-GA by CXCR4-CT: OR 7...
June 20, 2018: Molecular Biology Reports
Janis A Müller, Anna Glöckle, Ali Gawanbacht, Matthias Geyer, Jan Münch, Frank Kirchhoff
VIRIP has been identified as natural HIV-1 inhibitor targeting the gp41 fusion peptide. An optimized analogue (VIR-576) was effective in a phase I/II clinical trial and initial studies showed that HIV-1 resistance to VIRIP-based inhibitors has a high genetic barrier. Partially resistant CXCR4(X4)-tropic HIV-1 NL4-3 variants could be obtained, however, after more than 15 months of passaging in MT-4 cells in the presence of another derivative (VIR-353). Sequence analysis identified the accumulation of seven mutations across the HIV-1 envelope glycoprotein but outside of the gp41 fusion peptide...
June 20, 2018: Journal of Virology
Kongyang Ma, Jingyi Li, Xiaohui Wang, Xiang Lin, Wenhan Du, Xi Yang, Fangxiang Mou, Yongfei Fang, Yanbin Zhao, Xiaoping Hong, Kwok Wah Chan, Xiaoming Zhang, Dongzhou Liu, Lingyun Sun, Liwei Lu
OBJECTIVES: In patients with systemic lupus erythematosus (SLE), immune tolerance breakdown leads to autoantibody production and immune-complex glomerulonephritis. This study aimed to identify pathogenic plasma cells (PC) in the development of lupus nephritis. METHODS: PC subsets in peripheral blood and renal tissue of patients with SLE and lupus mice were examined by flow cytometry and confocal microscopy, respectively. Sorting-purified PCs from lupus mice were adoptively transferred into Rag2 -deficient recipients, in which immune-complex deposition and renal pathology were investigated...
June 20, 2018: Annals of the Rheumatic Diseases
Z Ouyang, J P Sun, X L Tian, M X Chen, J J Zhai
Objective: To investigate the expressions and significances of SDF-1 and its receptor CXCR-4 in endometriosis. Methods: 50 hysteromyoma patients treated at Beijing Tongren Hospital, Capital Medical University between 1(st) January 2016 and 31(st) December 2017 were divided into control group, that is, non-endometriosis group, while another 50 endometriosis patients were divided into experimental group.The endometrial tissues, endometriosis lesions, and peritoneal fluid samples of hysteromyoma patients were collected by operation...
June 19, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
María José Moreno, Alberto Gallardo, Silvana Novelli, Ana Mozos, Marc Aragó, Miguel Ángel Pavón, María Virtudes Céspedes, Víctor Pallarès, Aïda Falgàs, Miguel Alcoceba, Oscar Blanco, Marcos Gonzalez-Díaz, Jorge Sierra, Ramon Mangues, Isolda Casanova
The CXCR4/CXCL12 axis has been extensively associated with different types of cancer correlating with higher aggressiveness and metastasis. In diffuse large B-cell lymphoma (DLBCL), the expression of the chemokine receptor CXCR4 is involved in the dissemination of malignant B cells and is a marker of poor prognosis. CXCR7 is a chemokine receptor that binds to the same ligand as CXCR4 and regulates de CXCR4-CXCL12 axis. These findings together with the report of CXCR7 prognostic value in several tumor types, led us to evaluate the expression of CXCR7 in diffuse large B-cell lymphoma biopsies...
2018: PloS One
Serkan Kuyumcu, Ebru Yilmaz, Fikret Büyükkaya, Zeynep Gözde Özkan, Seher Nilgün Ünal
A 52-year-old woman diagnosed with mycosis fungoides was referred for F-FDG PET/CT before treatment for the evaluation of disease severity. The patient also underwent Ga-pentixafor PET/CT for further evaluation. FDG uptake was observed in cervical, axillary, and pelvic lymph nodes and multiple widespread skin lesions throughout the body, suggestive of extensive involvement of mycosis fungoides. All lesions were visually identifiable with high target-to-background ratio on Ga-pentixafor PET/CT which demonstrated marked CXCR4 expression in all lesions that were detected using F-FDG PET/CT...
June 19, 2018: Clinical Nuclear Medicine
Rosalie M Sterner, Kimberly N Kremer, Amel Dudakovic, Jennifer J Westendorf, Andre J van Wijnen, Karen E Hedin
The bone marrow microenvironment harbors and protects leukemic cells from apoptosis-inducing agents via mechanisms that are incompletely understood. We previously showed SDF-1 (CXCL-12), a chemokine readily abundant within the bone marrow microenvironment, induces apoptosis in acute myeloid leukemia (AML) cells that express high levels of the SDF-1 receptor CXCR4. However, differentiating osteoblasts found within this niche protect cocultured AML cells from apoptosis. Additionally, this protection was abrogated upon treatment of the differentiating osteoblasts with histone deacetylase inhibitors (HDACi)...
June 18, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Bruck Taddese, Madeline Deniaud, Antoine Garnier, Asma Tiss, Hajer Guissouma, Hervé Abdi, Daniel Henrion, Marie Chabbert
Chemokines and their receptors (members of the GPCR super-family) are involved in a wide variety of physiological processes and diseases; thus, understanding the specificity of the chemokine receptor family could help develop new receptor specific drugs. Here, we explore the evolutionary mechanisms that led to the emergence of the chemokine receptors. Based on GPCR hierarchical classification, we analyzed nested GPCR sets with an eigen decomposition approach of the sequence covariation matrix and determined three key residues whose mutation was crucial for the emergence of the chemokine receptors and their subsequent divergence into homeostatic and inflammatory receptors...
June 18, 2018: PLoS Computational Biology
Wei Shen, Ru Ba, Yan Su, Yang Ni, Dongsheng Chen, Wei Xie, Samuel J Pleasure, Chunjie Zhao
Abnormalities in cortical interneurons are closely associated with neurological diseases. Most patients with Foxg1 syndrome experience seizures, suggesting a possible role of Foxg1 in the cortical interneuron development. Here, by conditional deletion of Foxg1, which was achieved by crossing Foxg1fl/fl with the Gad2-CreER line, we found the postnatal distributions of somatostatin-, calretinin-, and neuropeptide Y-positive interneurons in the cortex were impaired. Further investigations revealed an enhanced dendritic complexity and decreased migration capacity of Foxg1-deficient interneurons, accompanied by remarkable downregulation of Dlx1 and CXCR4...
April 18, 2018: Cerebral Cortex
Tamara Ruegamer, Rebecca Hoffmann, Anette Rohrhofer, Franz Audebert, Bernd Salzberger, Klaus Korn, Philipp Schuster, Jutta Eichler, Barbara Schmidt
OBJECTIVE(S): Up to 40% of HIV-1 infected individuals are coinfected with human pegivirus type 1 (HPgV-1). The majority, but not all studies reported a beneficial effect of HPgV-1 coinfection on HIV-1 disease progression. So far, the impact of different HPgV-1 genotypes (GT) on different HIV-1 subtypes remains unclear. METHODS: Peptides derived from HPgV-1 envelope protein E2, and representing different viral genotypes, were synthesized using Fmoc/t-Bu based solid phase peptide synthesis...
June 14, 2018: AIDS
Kyle Crassini, Tahni Pyke, Yandong Shen, William S Stevenson, Richard I Christopherson, Stephen P Mulligan, Oliver Giles Best
The Raf-1 kinase inhibitory protein (RKIP) is an important regulatory element in multiple signaling pathways, including MAPK-ERK1/2. We investigated whether targeted disruption of RKIP is a therapeutic option for chronic lymphocytic leukemia (CLL). The RKIP inhibitor locostatin-induced apoptosis of CLL cells, irrespective of poor prognostic indications or treatment history. Locostatin down-regulated MAPK-ERK1/2 and AKT phosphorylation, decreased expression of the chemokine receptor CXCR4 (p = .04) and reduced the migratory capacity of CLL cells toward stroma-derived factor 1α (SDF-1α, p = ...
June 18, 2018: Leukemia & Lymphoma
N M Agalave, S AbdelMoaty, P Lundback, U Andersson, H Harris, C I Svensson
Aims Increasing evidence indicates that extracellular high mobility group box-1 protein (HMGB1) is involved in the pathogenesis of inflammatory and autoimmune disease. Data from our laboratory demonstrates that HMGB1 contributes to nociceptive behavior in a model of rheumatoid arthritis-induced pain. HMGB1 binds to multiple receptors, including toll like receptor (TLR) 2, TLR4 and receptor for advanced glycation end products (RAGE). When the cysteine in position C106 is in the reduced thiol form and C23 and C45 are engaged in a disulfide bridge (disulfide HMGB1), the molecule functions as a cytokine-inducing TLR4 ligand...
December 29, 2017: Scandinavian Journal of Pain
Iva Hopkins Navratilova, Tonia Aristotelous, Louise E Bird, Andrew L Hopkins
Biophysical screening techniques, such as surface plasmon resonance, enable detailed kinetic analysis of ligands binding to solubilised G-protein coupled receptors. The activity of a receptor solubilised out of the membrane is crucially dependent on the environment in which it is suspended. Finding the right conditions is challenging due to the number of variables to investigate in order to determine the optimum solubilisation buffer for any given receptor. In this study we used surface plasmon resonance technology to screen a variety of solubilisation conditions including buffers and detergents for two model receptors: CXCR4 and CCR5...
June 14, 2018: Analytical Biochemistry
E Mammadova-Bach, T Rupp, C Spenlé, I Jivkov, P Shankaranarayanan, A Klein, L Pisarsky, A Méchine-Neuville, G Cremel, M Kedinger, O De Wever, N Ambartsumian, S Robine, E Pencreach, D Guenot, P Simon-Assmann, J G Goetz, G Orend, O Lefebvre
Tumor stroma remodeling is a key feature of malignant tumors and can promote cancer progression. Laminins are major constituents of basement membranes that physically separate the epithelium from the underlying stroma. By employing mouse models expressing high and low levels of the laminin α1 chain (LMα1), we highlighted its implication in a tumor-stroma crosstalk, thus leading to increased colon tumor incidence, angiogenesis and tumor growth. The underlying mechanism involves attraction of carcinoma-associated fibroblasts by LMα1, VEGFA expression triggered by the complex integrin α2β1-CXCR4 and binding of VEGFA to LM-111, which in turn promotes angiogenesis, tumor cell survival and proliferation...
June 15, 2018: Biology of the Cell
Jing Liu, Jia-Xin Shen, Hua-Tao Wu, Xiao-Li Li, Xiao-Fen Wen, Cai-Wen Du, Guo-Jun Zhang
PURPOSE: Extracellular matrix (ECM) is an important component of tumor microenvironment and plays critical roles in cancer development and metastasis, in which collagen is the major structural protein. Collagen type I alpha 1 (COL1A1) is reportedly associated with the development of several human diseases. However, the functions and mechanisms of cellular expression of COL1A1 in breast cancer remain unknown. The purpose of this study is to investigate the cellular expression of COL1A1 in breast cancer cells and patients, and its role in the development and metastasis of breast cancer...
May 2018: Discovery Medicine
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