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https://www.readbyqxmd.com/read/29455558/investigational-immunosuppressants-in-early-stage-clinical-trials-for-the-treatment-of-multiple-sclerosis
#1
Alberto Gajofatto, Marco Turatti
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system with an immune mediated pathogenesis. Several therapies that suppress or modulate diverse immune system functions have been used for decades with the aim of modifying the disease course. However, these treatments have either limited efficacy or potentially serious adverse events that prevent first-line use on large scale. Areas covered. The aim of the present article is to review ongoing or recently completed clinical trials investigating immunosuppressive drugs for MS...
February 19, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29453251/a-novel-adipokine-fam19a5-inhibits-postinjury-neointima-formation-through-sphingosine-1-phosphate-receptor-2
#2
Yingbao Wang, Dixin Chen, Yan Zhang, Pingzhang Wang, Can Zheng, Songyang Zhang, Bing Yu, Lu Zhang, Guizhen Zhao, Baihui Ma, Zeyu Cai, Nan Xie, Shiyang Huang, Ziyi Liu, Xiaoning Mo, Youfei Guan, Xian Wang, Yi Fu, Dalong Ma, Ying Wang, Wei Kong
Background -Obesity plays crucial roles in the development of cardiovascular diseases (CVDs). However, the mechanisms that link obesity and CVDs remain elusive. Compelling evidence indicates that adipokines play an important role in obesity-related CVDs. Here, we found a new adipokine named family with sequence similarity 19, member A5 (FAM19A5), a protein with unknown function that was predicted to be distantly related to the CC-chemokine family. We aimed to test whether adipose-derived FAM19A5 regulates vascular pathology upon injury...
February 16, 2018: Circulation
https://www.readbyqxmd.com/read/29452570/s1p-transporter-spns2-regulates-proper-postnatal-retinal-morphogenesis
#3
Chao Fang, Ganlan Bian, Pan Ren, Jie Xiang, Jun Song, Caiyong Yu, Qian Zhang, Ling Liu, Kun Chen, Fangfang Liu, Kun Zhang, Chunfeng Wu, Ruixia Sun, Dan Hu, Gong Ju, Jian Wang
Spinster homolog 2 (SPNS2) is the membrane transporter of sphingosine-1-phosphate (S1P), and it participates in several physiologic processes by activating different S1P receptors (S1PRs). However, its functions in the nervous system remain largely unclear. We explored the important role of SPNS2 in the process of retinal morphogenesis using a spns2-deficient rat model. In the absence of the functional SPNS2 transporter, we observed progressively aggravating laminar disorganization of the epithelium at the postnatal stage of retinal development...
February 8, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29452218/tnf%C3%AE-disrupts-blood-brain-barrier-integrity-to-maintain-prolonged-depressive-like-behavior-in-mice
#4
Yuyan Cheng, Sachi Desse, Ana Martinez, Ryan J Worthen, Richard S Jope, Eleonore Beurel
Recovery from major depressive disorder is difficult, particularly in patients who are refractory to antidepressant treatments. To examine factors that regulate recovery, we developed a prolonged learned helplessness depression model in mice. After the induction of learned helplessness, mice were separated into groups that recovered or did not recover within 4 weeks. Comparisons were made between groups in hippocampal proteins, inflammatory cytokines, and blood brain barrier (BBB) permeability. Compared with mice that recovered and control mice, non-recovered mice displaying prolonged learned helplessness had greater hippocampal activation of glycogen synthase kinase-3 (GSK3), higher levels of tumor necrosis factor-α (TNFα), interleukin-17A, and interleukin-23, increased permeability of the blood brain barrier (BBB), and lower levels of the BBB tight junction proteins occludin, ZO1, and claudin-5...
February 13, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29451476/-sphingosine-1-phosphate-as-a-new-regulator-of-mitosis
#5
Olivier Cuvillier, Anastassia Hatzoglou
No abstract text is available yet for this article.
February 2018: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/29450744/high-density-lipoprotein-hdl-promotes-angiogenesis-via-s1p3-dependent-vegfr2-activation
#6
Fengyan Jin, Nina Hagemann, Li Sun, Jiang Wu, Thorsten R Doeppner, Yun Dai, Dirk M Hermann
High-density lipoprotein (HDL) has previously been shown to promote angiogenesis. However, the mechanisms by which HDL enhances the formation of blood vessels remain to be defined. To address this, the effects of HDL on the proliferation, transwell migration and tube formation of human umbilical vein endothelial cells were investigated. By examining the abundance and phosphorylation (i.e., activation) of the vascular endothelial growth factor receptor VEGFR2 and modulating the activity of the sphingosine-1 phosphate receptors S1P1-3 and VEGFR2, we characterized mechanisms controlling angiogenic responses in response to HDL exposure...
February 15, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29446730/salvaging-the-ischemic-heart-gi-coupled-receptors-in-mast-cells-activate-a-pkc%C3%AF-aldh2-pathway-providing-anti-ras-cardioprotection
#7
Alice Marino, Roberto Levi
BACKGROUND: Excessive norepinephrine (NE) release in the ischemic heart elicits severe and often lethal arrhythmias. Resident cardiac mast cells synthesize and store active renin, which is released upon degranulation, causing the activation of a local cardiac renin-angiotensin system (RAS) responsible for NE release and consequent arrhythmias. Toxic aldehydes, known to be formed by lipid peroxidation in ischemia/reperfusion (I/R), have been shown to degranulate mast cells and activate a local RAS...
February 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29441205/sphingosine-kinase-2-supports-the-development-of-bcr-abl-independent-acute-lymphoblastic-leukemia-in-mice
#8
Vicki Xie, Daochen Tong, Craig T Wallington-Beddoe, Ken F Bradstock, Linda J Bendall
Background: Sphingosine kinase (SphK) 2 has been implicated in the development of a range of cancers and inhibitors of this enzyme are currently in clinical trial. We have previously demonstrated a role for SphK2 in the development of acute lymphoblastic leukemia (ALL). Methods: In this and our previous study we use mouse models: in the previous study the disease was driven by the proto-oncogene BCR/ABL1, while in this study cancer risk was elevated by deletion of the tumor suppressor ARF...
2018: Biomarker Research
https://www.readbyqxmd.com/read/29439248/transient-receptor-potential-vanilloid-4-activation-induced-increase-in-glycine-activated-current-in-mouse-hippocampal-pyramidal-neurons
#9
Mengwen Qi, Chunfeng Wu, Zhouqing Wang, Li Zhou, Chen Men, Yimei Du, Songming Huang, Lei Chen, Ling Chen
BACKGROUND/AIMS: Glycine plays an important role in regulating hippocampal inhibitory/ excitatory neurotransmission through activating glycine receptors (GlyRs) and acting as a co-agonist of N-methyl-d-aspartate-type glutamate receptors. Activation of transient receptor potential vanilloid 4 (TRPV4) is reported to inhibit hippocampal A-type γ-aminobutyric acid receptor, a ligand-gated chloride ion channel. GlyRs are also ligand-gated chloride ion channels and this paper aimed to explore whether activation of TRPV4 could modulate GlyRs...
February 7, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29433094/fingolimod-reduces-the-clinical-expression-of-active-demyelinating-lesions-in-ms
#10
Signoriello Elisabetta, Landi Doriana, Monteleone Fabrizia, Saccà Francesco, Nicoletti Carolina Gabri, Buttari Fabio, Sica Francesco, Marfia Girolama Alessandra, Di Iorio Giuseppe, Lus Giacomo, Centonze Diego
BACKGROUND: Fingolimod is a modulator of Central and peripheral sphingosine pathways, which is currently approved for treatment of Multiple Sclerosis (MS). In animal models it reduces inflammation, but it is also able to potentiate glutamatergic transmission and synaptic plasticity. We aimed to explore whether Fingolimod is able to modify the clinical expression of new demyelinating lesions with respect to IFNβ-1a in relapsing remitting MS (RRMS) patients suboptimal responders to IFNβ-1a...
February 5, 2018: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29431203/changing-the-threshold-signals-and-mechanisms-of-mast-cell-priming
#11
REVIEW
Ivana Halova, Elin Rönnberg, Lubica Draberova, Harissios Vliagoftis, Gunnar P Nilsson, Petr Draber
Mast cells play a key role in allergy and other inflammatory diseases involving engagement of multivalent antigen with IgE bound to high-affinity IgE receptors (FcεRIs). Aggregation of FcεRIs on mast cells initiates a cascade of signaling events that eventually lead to degranulation, secretion of leukotrienes and prostaglandins, and cytokine and chemokine production contributing to the inflammatory response. Exposure to pro-inflammatory cytokines, chemokines, bacterial and viral products, as well as some other biological products and drugs, induces mast cell transition from the basal state into a primed one, which leads to enhanced response to IgE-antigen complexes...
March 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29430921/maldi-ms-imaging-reveals-asymmetric-spatial-distribution-of-lipid-metabolites-from-bisphenol-s-induced-nephrotoxicity
#12
Chao Zhao, Peisi Xie, Ting Yong, Hailin Wang, Arthur Chung, Zongwei Cai
With the continuous exposure of environmental pollutants in organisms, determination of abundance variation and spatial distribution of lipids might expand our understanding of toxicological mechanisms occurring in kidney. Herein, an integrated method involving mass spectrometry (MS)-based lipidomics and matrix-assisted laser desorption/ionization-MS imaging (MALDI-MSI) was developed for the study of nephrotoxicity in mice exposed to 10 and 100 μg bisphenol S (BPS)/kg body weight/day. The BPS exposure remarkable perturbed abundances of 91 potential markers that mainly involved in five metabolic pathways...
February 12, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29428730/targeting-sphingosine-kinase-2-by-abc294640-inhibits-human-skin-squamous-cell-carcinoma-cell-growth
#13
Jianbo Zhou, Jin Chen, Huanmiao Yu
The activity of ABC294640, a small-molecular sphingosine kinase 2 (SphK2) inhibitor, in human skin squamous cell carcinoma (SCC) cells was tested in this study. SphK2 mRNA and protein are expressed in established (A431 cell line) and primary human skin SCC cells. ABC294640 dose-dependently inhibited survival, cell cycle progression and proliferation of skin SCC cells. Furthermore, ABC294640 induced caspase-3/-9 and apoptosis activation in skin SCC cells. The SphK2 inhibitor was however non-cytotoxic to SphK2-null skin melanocytes, keratinocytes and fibroblasts...
February 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29428555/the-inflammatory-molecule-sphingosine-1-phosphate-is-not-effective-to-evoke-or-sensitize-cough-in-na%C3%A3-ve-guinea-pigs
#14
Simona Svajdova, Lenka Mazurova, Mariana Brozmanova
Sphingosine-1-phosphate (S1P) is an inflammatory mediator increased in the tissue in the number of inflammatory conditions. Preliminary data indicate that the vagal afferent neurons express several S1P receptors including S1PR2-3. We therefore evaluated the hypothesis that S1P induces cough and/or enhances the cough evoked by other tussive stimuli (TRPA1 and TRPV1 activators) in naïve guinea pigs. Inhalation of S1P in the concentrations of 0.1 mM and 1 mM did not evoke cough. Preinhalation and continuing inhalation of S1P (1 mM) during citric acid (0...
February 8, 2018: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/29427804/escmid-study-group-for-infections-in-compromised-hosts-esgich-consensus-document-on-the-safety-of-targeted-and-biological-therapies-an-infectious-diseases-perspective-immune-checkpoint-inhibitors-cell-adhesion-inhibitors-sphingosine-1-phosphate-receptor-modulators
#15
REVIEW
Gil Redelman-Sidi, Olivier Michielin, Carlos Cervera, Camillo Ribi, José María Aguado, Mario Fernández-Ruiz, Oriol Manuel
BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of immune checkpoint inhibitors, LFA-3-targeted agents, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family...
February 7, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29416779/the-sphingosine-kinase-2-inhibitor-abc294640-inhibits-cervical-carcinoma-cell-growth
#16
Ling Xu, Longmei Jin, Baohua Yang, Lifeng Wang, Ziyin Xia, Qian Zhang, Jun Xu
ABC294640 is a specific sphingosine kinase 2 (SphK2) inhibitor. The anti-cervical carcinoma activity by ABC294640 was tested in this study. ABC294640 inhibited in vitro growth of the established (C33A and HeLa lines) and primary human cervical carcinoma cells. The SphK2 inhibitor also induced G1-S arrest and apoptosis in cervical carcinoma cells. It was yet non-cytotoxic to SphK2-low human cervical epithelial cells. ABC294640 inhibited SphK activation, causing sphingosine-1-phosphate depletion, signal transducer and activator of transcription 3 in-activation and ceramide production...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29415945/validating-a-selective-s1p1-receptor-modulator-syl930-for-psoriasis-treatment
#17
Ming Ji, Nina Xue, Fangfang Lai, Xiaoying Zhang, Sen Zhang, Yuchen Wang, Jing Jin, Xiaoguang Chen
Psoriasis is a chronic inflammatory skin disease characterized by red, scaly and raised plaques. Thus far, T-cell infiltration is one of the most prominent pathogenic triggers, however, the exact molecular mechanisms underlying psoriasis have not been clearly established. Sphingolipid sphingosine-1-phosphate (S1P) is a lysophospholipid regulator modulating a variety of immune cell trafficking via interactions with its cognate receptors, S1P1-5. Activation of S1P signaling has recently emerged as a novel therapeutic avenue for psoriasis treatment...
February 7, 2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29411220/novel-therapies-and-treatment-strategies-for-patients-with-inflammatory-bowel-disease
#18
REVIEW
Marjolijn Duijvestein, Robert Battat, Niels Vande Casteele, Geert R D'Haens, William J Sandborn, Reena Khanna, Vipul Jairath, Brian G Feagan
PURPOSE OF REVIEW: This article reviews current treatment options and strategies and provides an update on the status of drug development programs of new therapeutic agents for inflammatory bowel diseases (IBD). RECENT FINDINGS: In the past two decades, tumor necrosis factor antagonist therapy has given clinicians better treatment options. However, not all patients respond to induction therapy with these agents, and of those initially responding, up to 40% ultimately lose response due to suboptimal drug exposure (e...
February 6, 2018: Current Treatment Options in Gastroenterology
https://www.readbyqxmd.com/read/29410409/exosome-mimetic-nanovesicles-from-hepatocytes-promote-hepatocyte-proliferation-in-vitro-and-liver-regeneration-in-vivo
#19
Jun-Yi Wu, An-Lai Ji, Zhong-Xia Wang, Guang-Hui Qiang, Zhen Qu, Jun-Hua Wu, Chun-Ping Jiang
The liver has great regenerative capacity after functional mass loss caused by injury or disease. Many studies have shown that primary hepatocyte-derived exosomes, which can deliver biological information between cells, promote the regenerative process of the liver. However, the yield of exosomes is very limited. Recent studies have demonstrated that exosome-mimetic nanovesicles (NVs) can be prepared from cells with almost 100 times the production yield compared with exosomes. Thus, this study investigated the therapeutic capacity of exosome-mimetic NVs from primary hepatocytes in liver regeneration...
February 6, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29408487/probing-the-role-of-ceramide-hydroxylation-in-skin-barrier-lipid-models-by-2h-solid-state-nmr-spectroscopy-and-x-ray-powder-diffraction
#20
Andrej Kováčik, Alexander Vogel, Juliane Adler, Petra Pullmannová, Kateřina Vávrová, Daniel Huster
In this work, we studied model stratum corneum lipid mixtures composed of the hydroxylated skin ceramides N-lignoceroyl 6-hydroxysphingosine (Cer[NH]) and α-hydroxylignoceroyl phytosphingosine (Cer[AP]). Two model skin lipid mixtures of the composition Cer[NH] or Cer[AP], N-lignoceroyl sphingosine (Cer[NS]), lignoceric acid (C24:0) and cholesterol in a 0.5:0.5:1:1 molar ratio were compared. Model membranes were investigated by differential scanning calorimetry and 2H solid-state NMR spectroscopy at temperatures from 25 °C to 80 °C...
February 2, 2018: Biochimica et Biophysica Acta
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