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Quan Zhou, Li Hong, Jing Wang
PURPOSE: The aim of this study was to elucidate the molecular mechanisms and to identify the key genes and pathways for pelvic organ prolapse (POP) using bioinformatics analysis. METHODS: The microarray data for GSE53868 included 12 POP and 12 non-POP anterior vaginal wall samples. Differentially expressed genes (DEGs) were identified by GEO2R online tool. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database, and a DEG-associated protein-protein interaction (PPI) network was constructed using STRING and visualized in Cytoscape...
March 15, 2018: Archives of Gynecology and Obstetrics
Kurt A Zimmerman, Cheng Jack Song, Nancy Gonzalez-Mize, Zhang Li, Bradley K Yoder
Hepatorenal fibrocystic disease (HRFCD) is characterized by cysts in the kidney and liver with associated fibrosis and is the result of defects in proteins required for cilia function or assembly. Previous reports indicate that macrophages, mainly M2-like macrophages, contribute to HRFCD, although the origin (yolk-sac derived resident macrophages vs bone-marrow derived infiltrating macrophages) and contribution of these cells to the observed phenotypes is unknown. Herein, we utilize a congenital model of cilia dysfunction (IFT88Orpk ) to study the importance of macrophages in HRFCD...
March 15, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Sagus Sampath, Haejung Won, Erminia Massarelli, Min Li, Paul Frankel, Nayana Vora, Lalit Vora, Ellie Maghami, Marcin Kortylewski
Immunomodulation contributes to the antitumor efficacy of the fractionated radiation therapy (RT). Here, we describe immune effects of RT with concurrent systemic cisplatin or cetuximab treatment of patients with stage III-IV head and neck squamous cell carcinoma (HNSCC). Using longitudinally collected blood samples, we identified significant changes in cytokines/chemokines and immune cell populations compared to immune-related gene expression profiles in peripheral blood mononuclear cells (PBMCs). The 7-week combinatorial RT resulted in gradual elevation of proinflammatory mediators (IFNγ, IL-6, TNFɑ, CCL2), while levels of IL-12, cytokine essential for antitumor immune responses, were decreased...
February 16, 2018: Oncotarget
Takuya Tsubaki, Tetsuya Kadonosono, Shimon Sakurai, Tadashi Shiozawa, Toshiki Goto, Shiori Sakai, Takahiro Kuchimaru, Takeharu Sakamoto, Hitomi Watanabe, Gen Kondoh, Shinae Kizaka-Kondoh
The immunosuppressive tumor microenvironment is a hallmark of cancer. Myeloid-derived suppressor cells (MDSCs) are CD11b+ Gr-1+ tumor-infiltrating immature myeloid cells that strongly mediate tumor immunosuppression. The CD11b+ Gr-1+ cells are a heterogeneous cell population, and the impacts of each subpopulation on tumor progression are not yet completely understood. In the present study, we identified a novel subpopulation of CD11b+ Gr-1+ cells from murine lung carcinoma tumors according to their strongly adherent abilities...
February 16, 2018: Oncotarget
Zachary Curry, Jenny Wilkerson, Deniz Bagdas, Sarah Kyte, Nipa Patel, Giulia Donvito, Mohammed A Mustafa, Justin Poklis, Micah Niphakis, Ku-Lung Hsu, Benjamin F Cravatt, David A Gewirtz, M Imad Damaj, Aron H Lichtman
Although paclitaxel effectively treats various cancers, its debilitating peripheral neuropathic pain side effects often persist long after treatment has ended. Therefore, a compelling need exists for the identification of novel pharmacologic strategies to mitigate this condition. As inhibitors of monoacylglycerol lipase (MAGL), the primary hydrolytic enzyme of the endogenous cannabinoid 2-arachidonyolglycerol, produce antinociceptive effects in numerous rodent models of pain, we investigated whether inhibitors of this enzyme (i...
March 14, 2018: Journal of Pharmacology and Experimental Therapeutics
Danh T Tran, Scott Esckilsen, Jennifer Mulligan, Shikhar Mehrotra, Carl Atkinson, Satish N Nadig
BACKGROUND: Microvascular endothelial cells (ECs) are central to an allograft's immunogenicity. Cold ischemia and reperfusion injury associated with static cold storage and warm reperfusion activates ECs and increases the immunogenicity of the allograft. Following reperfusion, mitochondrial permeability transition pore (mPTP) opening contributes to mitochondrial dysfunction in the allograft, which correlates to alloimmune rejection. Current understanding of this relationship, however, centers on the whole allograft instead of ECs...
March 10, 2018: Transplantation
Nilisha Fernando, Riccardo Natoli, Tanja Racic, Yvette Wooff, Jan Provis, Krisztina Valter
The complement system is highly implicated in both the prevalence and progression of Age-Related Macular Degeneration (AMD). Complement system inhibitors therefore have potential therapeutic value in managing excessive activation of the complement pathways in retinal degenerations. The vaccinia virus complement control protein (VCP) has been shown to be effective as a complement inhibitor in neuroinflammatory models including traumatic brain injury and spinal cord injury. We aimed to investigate the potential of VCP as a therapeutic molecule for retinal degenerations...
2018: PloS One
Peter M Grace, Xiaohui Wang, Keith A Strand, Michael V Baratta, Yingning Zhang, Erika L Galer, Hang Yin, Steven F Maier, Linda R Watkins
The absence of selective pharmacological tools is a major barrier to the in vivo study of microglia. To address this issue, we developed a Gq - and Gi -coupled Designer Receptor Exclusively Activated by a Designer Drug (DREADD) to enable selective stimulation or inhibition of microglia, respectively. DREADDs under a CD68 (microglia/macrophage) promoter were intrathecally transfected via an AAV9 vector. Naïve male rats intrathecally transfected with Gq (stimulatory) DREADDs exhibited significant allodynia following intrathecal administration of the DREADD-selective ligand clozapine-N-oxide (CNO), which was abolished by intrathecal interleukin-1 receptor antagonist...
March 9, 2018: Experimental Neurology
Yvonne Hagenlocher, Sonja Gommeringer, Anna Held, Katharina Feilhauer, Jörg Köninger, Stephan C Bischoff, Axel Lorentz
PURPOSE: Inflammatory bowel disease (IBD) shows increasing prevalence over the last years. We propose that anti-inflammatory plant substances could be used as additional or alternative agents with good compliance in prevention and/or therapy of IBD and its complication intestinal fibrosis. We could recently show that the citrus flavonoid nobiletin acts anti-inflammatory on activation of intestinal mast cells. Here, we analysed the effects of nobiletin on inflammation and fibrosis in IL-10-/- colitis...
March 10, 2018: European Journal of Nutrition
Christian Herder, Andreas Schmitt, Florian Budden, André Reimer, Bernhard Kulzer, Michael Roden, Thomas Haak, Norbert Hermanns
BACKGROUND: Depressive disorders represent a frequent comorbidity of type 1 diabetes (T1D) and type 2 diabetes (T2D). Subclinical inflammation increases the risk of depressive symptoms in the general population, but the relationship appears complex and bidirectional, and longitudinal data from patients with diabetes are lacking. Therefore, this study aimed to analyse associations between changes in depressive symptoms and changes in biomarkers of inflammation in patients with T1D and T2D and to investigate the hypothesis that higher baseline levels of biomarkers of inflammation are related to a less pronounced reduction of depressive symptoms over time...
March 6, 2018: Psychoneuroendocrinology
Brian A Aguado, Rachel M Hartfield, Grace G Bushnell, Joseph T Decker, Samira M Azarin, Dhaval Nanavati, Matthew J Schipma, Shreyas S Rao, Robert S Oakes, Yining Zhang, Jacqueline S Jeruss, Lonnie D Shea
Primary tumor (PT) immune cells and pre-metastatic niche (PMN) sites are critical to metastasis. Recently, synthetic biomaterial scaffolds used as PMN mimics are shown to capture both immune and metastatic tumor cells. Herein, studies are performed to investigate whether the scaffold-mediated redirection of immune and tumor cells would alter the primary tumor microenvironment (TME). Transcriptomic analysis of PT cells from scaffold-implanted and mock-surgery mice identifies differentially regulated pathways relevant to invasion and metastasis progression...
March 9, 2018: Advanced Healthcare Materials
Christian Herder, Andreas Schmitt, Florian Budden, André Reimer, Bernhard Kulzer, Michael Roden, Thomas Haak, Norbert Hermanns
Subclinical inflammation has been implicated in the development of depression, a common comorbidity of type 1 diabetes (T1D) and type 2 diabetes (T2D). This study aimed to characterise the relationships between biomarkers of inflammation and depressive symptoms in T1D and T2D. Biomarkers of inflammation were measured in serum of participants with elevated depressive symptoms and T1D (n = 389, mean age 38 years, diabetes duration 15 ± 11 years) or T2D (n = 204, mean age 56 years, diabetes duration 13 ± 8 years)...
March 9, 2018: Translational Psychiatry
Valentina Bruno, Judit Svensson-Arvelund, Marie Rubér, Göran Berg, Emilio Piccione, Maria C Jenmalm, Jan Ernerudh
Low molecular weight heparin (LMWH) is widely used in recurrent miscarriage treatment. The anti-coagulant effects are established, while immunological effects are not fully known. Our aim was to assess LMWH effects on activation and polarization of central regulatory immune cells from healthy women, and on placenta tissues from women undergoing elective abortions. Isolated blood monocytes and T helper (Th) cells under different activation and polarizing conditions were cultured with or without LMWH. Flow cytometry showed that LMWH exposure induced increased expression of HLA-DR and CD206 in macrophages...
March 8, 2018: Scientific Reports
Yumiko Akai, Hidetaka Sadanari, Masaya Takemoto, Noboru Uchide, Tohru Daikoku, Naofumi Mukaida, Tsugiya Murayama
No abstract text is available yet for this article.
March 2018: Antiviral Research
Navin Sarin, Florian Engel, Florian Rothweiler, Jindrich Cinatl, Martin Michaelis, Roland Frötschl, Holger Fröhlich, Ganna V Kalayda
The major obstacle in the clinical use of the antitumor drug cisplatin is inherent and acquired resistance. Typically, cisplatin resistance is not restricted to a single mechanism demanding for a systems pharmacology approach to understand a whole cell's reaction to the drug. In this study, the cellular transcriptome of untreated and cisplatin-treated A549 non-small cell lung cancer cells and their cisplatin-resistant sub-line A549r CDDP2000 was screened with a whole genome array for relevant gene candidates...
March 7, 2018: International Journal of Molecular Sciences
Petr Dubový, Ilona Klusáková, Ivana Hradilová-Svíženská, Marek Joukal, Pere Boadas-Vaello
Peripheral nerve injuries (PNIs) may result in cellular and molecular changes in supraspinal structures possibly involved in neuropathic pain (NPP) maintenance. Activated glial cells in specific supraspinal subregions may affect the facilitatory role of descending pathways. Sterile chronic compression injury (sCCI) and complete sciatic nerve transection (CSNT) in rats were used as NPP models to study the activation of glial cells in the subregions of periaqueductal gray (PAG) and rostral ventromedial medulla (RVM)...
2018: Frontiers in Cellular Neuroscience
Alessio Polacchini, Damiano Girardi, Alessandra Falco, Nunzia Zanotta, Manola Comar, Nicola Alberto De Carlo, Enrico Tongiorgi
Chronic psychosocial stress at workplace is an important factor in the development of physical and mental illness. Objective biological measures of chronic stress are still lacking, but inflammatory response and growth factors are increasingly considered as potential stress biomarkers. Therefore, we investigated the relationship between psychophysical strain and serum levels of 48 chemokines, cytokines and growth factors measured using a multiplex immunoassay, and serum brain-derived neurotrophic factor (BDNF) measured by ELISA...
February 2018: Neurobiology of Stress
Hai-Yan Peng, Hua-Ping Li, Ming-Qing Li
Recent studies have revealed considerable dysfunction of vascular endothelial cells (VECs) and abnormal expression of microRNA (miR)-137 in women with gestational diabetes mellitus (GDM), and the aim of this study was to clarify the underlying mechanism and possible role of microRNA (miR)-137 in dysfunction of VECs during GDM. We found increased levels of miR-137 in the plasma of GDM women and high-glucose (HG)-exposed HUVECs. Upregulating miR-137 in HUVECs elevated the chemokine (C-C motif) ligand 2 (CCL2) secretion and enhanced the chemotaxis and adhesion of U937 and THP-1 (two human acute monocytic leukemia cell lines) cells to HUVECs in a co-culture system...
March 2, 2018: Microvascular Research
Eanna P Connaughton, Serika Naicker, Shirley A Hanley, Stephanie M Slevin, John K Eykelenboom, Noel F Lowndes, Timothy O'Brien, Rhodri Ceredig, Matthew D Griffin, Michael C Dennedy
Human blood monocytes are sub-classified as classical, intermediate and non-classical. In this study, it was shown that conventionally-defined human intermediate monocytes (IM) can be divided into two distinct subpopulations with mid- and high-level surface expression of HLA-DR (referred to as DRmid and DRhi IM). These IM subpopulations were phenotypically and functionally characterized in healthy adult blood by flow cytometry, migration assays and lipoprotein uptake assays. Their absolute numbers and proportions were then compared in blood samples from obese and non-obese adults...
March 5, 2018: Immunology and Cell Biology
Lara A Aqrawi, Janicke Liaaen Jensen, Gunnvor Øijordsbakken, Ann-Kristin Ruus, Ståle Nygård, Marit Holden, Roland Jonsson, Hilde Kanli Galtung, Kathrine Skarstein
A characteristic feature of primary Sjögren's syndrome (pSS) is the destruction of salivary and lacrimal glands mediated by mononuclear cell infiltration. Adipocytes can also occupy a large portion of the salivary gland (SG) tissue area, although little is known about their significance in pSS. We have previously investigated adipose tissue infiltration in SG biopsies from pSS patients and non-SS sicca controls. Our findings indicated the distinct incidence of adipose tissue replacement in pSS patients, where adipocytes were detected in interleukin (IL) 6 rich regions...
March 5, 2018: Autoimmunity
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