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Salvador Alonso, Daniela Hernandez, Yu-Ting Chang, Christian D Gocke, Megan McCray, Ravi Varadhan, William H Matsui, Richard J Jones, Gabriel Ghiaur
Interactions between multiple myeloma (MM) cells and the BM microenvironment play a critical role in bortezomib (BTZ) resistance. However, the mechanisms involved in these interactions are not completely understood. We previously showed that expression of CYP26 in BM stromal cells maintains a retinoic acid-low (RA-low) microenvironment that prevents the differentiation of normal and malignant hematopoietic cells. Since a low secretory B cell phenotype is associated with BTZ resistance in MM and retinoid signaling promotes plasma cell differentiation and Ig production, we investigated whether stromal expression of the cytochrome P450 monooxygenase CYP26 modulates BTZ sensitivity in the BM niche...
October 24, 2016: Journal of Clinical Investigation
Zhi-Dan Fan, Ya-Yuan Zhang, Yi-Hong Guo, Na Huang, Hui-Hui Ma, Hui Huang, Hai-Guo Yu
Interleukin (IL)-17 producing T helper (Th17) cells are major effector cells in the pathogenesis of rheumatoid arthritis (RA). The P2X7 receptor (P2X7R) has emerged as a potential site in the regulation of inflammation in RA but little is known of its functional role on the differentiation of Th17 cells. This study investigates the in vitro and in vivo effects of P2X7R on Th17 cell differentiation during type II collagen (CII) induced experimental arthritis model. In CII-treated dendritic cells (DCs) and DC/CD4(+) T coculture system, pretreatment with pharmacological antagonists of P2X7R (Suramin and A-438079) caused strong inhibition of production of Th17-promoting cytokines (IL-1β, TGF-β1, IL-23p19 and IL-6)...
October 24, 2016: Scientific Reports
In Ae Chang, Hee Don Lim, Ki Joong Kim, Hwachul Shin, Uk Namgung
ETHNOPHARMACOLOGICAL RELEVANCE: Buyang Huanwu decoction (BYHWD) has been used in the traditional Chinese medicine for the treatment of cardiovascular and neurological symptoms, and recent experimental studies have begun to provide evidence showing its protective effects on neural cells. Yet, its function for the regenerative responses of axons in the peripheral nerve after injury is not known. AIM OF THE STUDY: The primary objective of the present study was to explore that BYHWD is involved in growth-promoting activity of the peripheral nerve axons after injury...
October 19, 2016: Journal of Ethnopharmacology
Jennifer Hennen, Brunhilde Blömeke
In vitro approaches address key steps of chemical-induced skin sensitization but there is uncertainty how keratinocytes, which play a crucial role not only regarding xenobiotic metabolism but also skin inflammation, impact on chemicals' potential and potency of dendritic cell activation. We investigated these aspects by coculturing THP-1 cells, as surrogate dendritic cells, with HaCaT keratinocytes. We tested our HaCaT/THP-1 model with a set of 14 sensitizers, containing 7 prohaptens, and 10 non-sensitizers...
October 21, 2016: ALTEX
Kuo-Hsun Chiu, Ling-Hui Wang, Tsung-Ting Tsai, Huan-Yao Lei, Pao-Chi Liao
The secreted proteins of bacteria are usually accompanied by virulence factors, which can cause inflammation and damage host cells. Identifying the secretomes arising from the interactions of bacteria and host cells could, therefore, increase understanding of the mechanisms during initial pathogenesis. The present study used a host-pathogen coculture system of Helicobacter pylori and monocytes (THP-1 cells) to investigate the secreted proteins associated with initial H. pylori pathogenesis. The secreted proteins from the conditioned media from H...
October 20, 2016: Journal of Proteome Research
Eleonora Bassino, Edoardo Vallariello, Franco Gasparri, Luca Munaron
The biological importance of circulatory blood supply and angiogenesis for hair growth is now well recognized, but the their regulatory mechanisms require more mechanistic investigation. In vitro cocultures and tricultures can be successfully employed to greatly improve our knowledge on paracrine crosstalk between cell types that populate the dermal-epidermal interface and cutaneous vasculature. Here we report that human dermal fibroblasts (NHDF) promote viability and proliferation of microvascular endothelial cells (HMVEC), while HMVEC are not mitogenic for NHDF...
October 20, 2016: Journal of Cellular Physiology
Pakchisa Khonsuphap, Prasit Pavasant, Rizky Aditya Irwandi, Chidchanok Leethanakul, Anjalee Vacharaksa
BACKGROUND: Prostaglandin E2 (PGE2) accumulates in inflamed periodontal tissue and induces the receptor activator of nuclear factor kappa-B ligand (RANKL)-RANK-osteoprotegerin (OPG) signaling associated with bone resorption. Although oral epithelial cells maintain tissue homeostasis, the role of these cells in RANKL regulation remains unknown. METHODS: To mimic inflamed condition, RANKL upregulation in human mandibular osteoblast-like cells (HMOBs) were stimulated with PGE2...
October 20, 2016: Journal of Periodontology
Rocío López-Posadas, Cristina Mascaraque, Raquel González, María D Suárez, Antonio Zarzuelo, Olga Martínez-Augustin, Fermín Sánchez de Medina
BACKGROUND: Statins have antiinflammatory effects at the cardiovascular level because of inhibition of prenylation, which also probably underlies their therapeutic effects in preclinical models of inflammatory bowel disease. Another inhibitor of prenylation, namely alendronate, reduces colitis in rodents. In this study, we aim to explore the therapeutic potential of second-generation, nitrogen-containing bisphosphonates in 3 preclinical models of colitis. METHODS: The trinitrobenzenesulfonic acid and dextran sulfate sodium models of rat colitis and the adoptive lymphocyte transfer model of colitis in mice were used...
November 2016: Inflammatory Bowel Diseases
Kenji Ueda, Teruhiko Beppu
Today, the frequency of discovery of new antibiotics in microbial culture is significantly decreasing. The evidence from whole-genome surveys suggests that many genes involved in the synthesis of unknown metabolites do exist but are not expressed under conventional cultivation conditions. Therefore, it is urgently necessary to study the conditions that make otherwise silent genes active in microbes. Here we overview the knowledge on the antibiotic production promoted by cocultivation of multiple microbial strains...
October 19, 2016: Journal of Antibiotics
Silvia Panzavolta, Paola Torricelli, Sonia Casolari, Annapaola Parrilli, Sofia Amadori, Milena Fini, Adriana Bigi
The systemic administration of bisphosphonates (BPs) for the treatment of metabolic diseases characterized by abnormal bone loss suffers from several adverse side effects, which can be reduced by implementation of alternative modes of administration. In this work, glutaraldehyde cross-linked gelatin scaffolds are proposed as delivery systems of calcium alendronate monohydrate (CaAL•H2 O). The 3D highly porous scaffolds display a relevant interconnected porosity (>94%), independently from CaAL•H2 O content (0, 3, and 6 wt%)...
October 17, 2016: Macromolecular Bioscience
Jennifer L Gori, Jason M Butler, Balvir Kunar, Michael G Poulos, Michael Ginsberg, Daniel J Nolan, Zachary K Norgaard, Jennifer E Adair, Shahin Rafii, Hans-Peter Kiem
: : Successful expansion of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) would benefit many HSPC transplantation and gene therapy/editing applications. However, current expansion technologies have been limited by a loss of multipotency and self-renewal properties ex vivo. We hypothesized that an ex vivo vascular niche would provide prohematopoietic signals to expand HSPCs while maintaining multipotency and self-renewal. To test this hypothesis, BM autologous CD34(+) cells were expanded in endothelial cell (EC) coculture and transplanted in nonhuman primates...
October 14, 2016: Stem Cells Translational Medicine
Francesca Deidda, Angela Amoruso, Serena Allesina, Marco Pane, Teresa Graziano, Mario Del Piano, Luca Mogna
GOALS: This study was undertaken to demonstrate the ability of Lactobacillus fermentum LF5 (DSM 32277) to inhibit in vitro different Candida species and Gardnerella vaginalis to weigh its potential effectiveness even in mixed vaginal infections. BACKGROUND: A wide female population is suffering from various vulvovaginal infections. These diseases are often associated with a decrease in the concentration of Lactobacilli in the vagina. Mixed vaginal infections represent >20% of women with vulvovaginal infection...
November 2016: Journal of Clinical Gastroenterology
Shu Harn Te, Boon Fei Tan, Janelle R Thompson, Karina Yew-Hoong Gin
Genomes of two filamentous benthic cyanobacteria were obtained from cocultures obtained from two freshwater lakes. The cultures were obtained by first growing cyanobacterial trichome on solid medium, followed by subculturing in freshwater media. Subsequent shotgun sequencing, de novo assembly, and genomic binning yielded almost complete genomes of Oscillatoriales USR 001 and Nostoc sp. MBR 210.
October 13, 2016: Genome Announcements
Lei Hu, Ying Wen, Junji Xu, Tingting Wu, Chunmei Zhang, Jinsong Wang, Jie Du, Songlin Wang
Mesenchymal stem cell (MSC)-mediated bone regeneration is used to replace lost bone. However, methods to accelerate the process and stabilize regenerated bone remain limited. Therefore, we investigated the effect of bisphosphonates (BPs) on the function of bone marrow mesenchymal stem cells (BMMSCs) to determine if they might enhance MSC-mediated bone regeneration. We isolated and cultured BMMSCs from BALB/c mice and treated the cells with 0.1, 0.5, 1, 5, or 10 μM zoledronic acid (ZA; Zometa, a commercially available BP)...
October 13, 2016: Stem Cells and Development
Zhao-Wei Ding, Yong-Ze Lu, Liang Fu, Jing Ding, Raymond J Zeng
In this study, the coculture system of denitrifying anaerobic methane oxidation (DAMO) microbes and anaerobic ammonium oxidation (anammox) bacteria was successfully enriched in a hollow-fiber membrane biofilm reactor (HfMBR) using freshwater sediment as the inoculum. The maximal removal rates of nitrate and ammonium were 78 mg N/L/day (131 mg N/m(2)/day) and 26 mg N/L/day (43 mg N/m(2)/day), respectively. Due to the high rate of methane mass transfer in HfMBR, the activity of DAMO archaea continued to increase during the enrichment period, indicating that HfMBR could be a powerful tool to enrich DAMO microorganisms...
October 12, 2016: Applied Microbiology and Biotechnology
Xi Fang, Matthew J Stroud, Kunfu Ouyang, Li Fang, Jianlin Zhang, Nancy D Dalton, Yusu Gu, Tongbin Wu, Kirk L Peterson, Hsien-Da Huang, Ju Chen, Nanping Wang
Adipose tissue is a key endocrine organ that governs systemic homeostasis. PPARγ is a master regulator of adipose tissue signaling that plays an essential role in insulin sensitivity, making it an important therapeutic target. The selective PPARγ agonist rosiglitazone (RSG) has been used to treat diabetes. However, adverse cardiovascular effects have seriously hindered its clinical application. Experimental models have revealed that PPARγ activation increases cardiac hypertrophy. RSG stimulates cardiac hypertrophy and oxidative stress in cardiomyocyte-specific PPARγ knockout mice, implying that RSG might stimulate cardiac hypertrophy independently of cardiomyocyte PPARγ...
October 6, 2016: JCI Insight
Marthe H R Ludtmann, Plamena R Angelova, Natalia N Ninkina, Sonia Gandhi, Vladimir L Buchman, Andrey Y Abramov
: Misfolded α-synuclein is a key factor in the pathogenesis of Parkinson's disease (PD). However, knowledge about a physiological role for the native, unfolded α-synuclein is limited. Using brains of mice lacking α-, β-, and γ-synuclein, we report that extracellular monomeric α-synuclein enters neurons and localizes to mitochondria, interacts with ATP synthase subunit α, and modulates ATP synthase function. Using a combination of biochemical, live-cell imaging and mitochondrial respiration analysis, we found that brain mitochondria of α-, β-, and γ-synuclein knock-out mice are uncoupled, as characterized by increased mitochondrial respiration and reduced mitochondrial membrane potential...
October 12, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Maria C Lebre, Pedro L Vieira, Man Wai Tang, Saïda Aarrass, Boy Helder, Thomas Newsom-Davis, Paul P Tak, Gavin R Screaton
Bone and cartilage destruction is one of the key manifestations of rheumatoid arthritis (RA). Although the role of T helper (Th)17 cells in these processes is clear, the role of IL-21-producing cells T cells has been neglected. We sought to investigate the role of IL-21 in RA by focusing on the functional characteristics of the main producers of this cytokine, synovial CD4(+)IL-21(+) T cells. We show that the frequency of both synovial fluid (SF) CD4(+)IL-21(+) or CD4(+)IL-21(+)TNF(+) T cells in patients with RA was significantly higher compared with patients with psoriatic arthritis (PsA)...
October 12, 2016: Journal of Leukocyte Biology
Shuhei Yamamoto, Kazunori Shimizu, Jiahui Fei, Hiroji Iwata, Mina Okochi, Hayao Nakanishi, Hiroyuki Honda
Phenotype-based analysis of circulating tumor cells (CTCs) is a promising approach to identification of new therapeutic targets and to elucidation of the biological properties. Nonetheless, ex vivo culturing of CTCs is still a technically challenging. Here, we developed a novel ex vivo culture method for CTCs using a fibroblast feeder layer and a magnetic coculture protocol. CTCs in the blood of a mouse metastasis model were labeled magnetically with magnetite nanoparticles. The labeled CTCs were isolated by a magnetic capture column and a size-selective capture filter...
October 12, 2016: Biotechnology Journal
Marie Maumus, Gautier Roussignol, Karine Toupet, Geraldine Penarier, Isabelle Bentz, Sandrine Teixeira, Didier Oustric, Mireille Jung, Olivier Lepage, Regis Steinberg, Christian Jorgensen, Danièle Noel
OBJECTIVE: Mesenchymal stem cells isolated from adipose tissue (ASC) have been shown to influence the course of osteoarthritis (OA) in different animal models and are promising in veterinary medicine for horses involved in competitive sport. The aim of this study was to characterize equine ASCs (eASCs) and investigate the role of interferon-gamma (IFNγ)-priming on their therapeutic effect in a murine model of OA, which could be relevant to equine OA. METHODS: ASC were isolated from subcutaneous fat...
2016: Frontiers in Immunology
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