Fingolimod Alters Tissue Distribution and Cytokine Production of Human and Murine Innate Lymphoid Cells

Sphingosine-1 phosphate receptor 1 (S1PR1) is expressed by lymphocytes and regulates their egress from secondary lymphoid organs. Innate lymphoid cell (ILC) family has been expanded with the discovery of group 1, 2 and 3 ILCs, namely ILC1, ILC2 and ILC3. ILC3 and ILC1 have remarkable similarity to CD4+ helper T cell lineage members Th17 and Th1, respectively, which are important in the pathology of multiple sclerosis (MS). Whether human ILC subsets express S1PR1 or respond to its ligands have not been studied. In this study, we used peripheral blood/cord blood and tonsil lymphocytes as a source of human ILCs. We show that human ILCs express S1PR1 mRNA and protein and migrate toward S1P receptor ligands. Comparison of peripheral blood ILC numbers between fingolimod-receiving and treatment-free MS patients revealed that, in vivo, ILCs respond to fingolimod, an S1PR1 agonist, resulting in ILC-penia in circulation. Similarly, murine ILCs responded to fingolimod by exiting blood and accumulating in the secondary lymph nodes. Importantly, ex vivo exposure of ILC3 and ILC1 to fingolimod or SEW2871, another S1PR1 antagonist, reduced production of ILC3- and ILC1- associated cytokines GM-CSF, IL-22, IL-17, and IFN-γ, respectively. Surprisingly, despite reduced number of lamina propria-resident ILC3s in the long-term fingolimod-treated mice, ILC3-associated IL-22, IL-17A, GM-CSF and antimicrobial peptides were high in the gut compared to controls, suggesting that its long term use may not compromise mucosal barrier function. To our knowledge, this is the first study to investigate the impact of fingolimod on human ILC subsets in vivo and ex vivo, and provides insight into the impact of long term fingolimod use on ILC populations

Chemical and Biological Diversity of the Leaf and Rhizome Volatiles of Acorus calamus L. from Turkey

Two different isolation techniques, conventional hydrodistillation (HD) and micro-steam distillation-solid-phase microextraction (MSD-SPME), have been used to analyze the volatile constituents from the leaves and rhizomes of Acorus calamus L. by gas chromatography (GC-FID) and gas chromatography coupled to mass spectrometry (GC-MS). In all the samples studied, phenylpropanoids (16.9-35.3 %) predominated by beta-asarone (15.3-16.3 % in rhizomes, 23.4-31.7 % in leaves) were the main constituent. In addition to phenylpropanoids, the acorane type sesquiterpene acorenone B (7.4-16.4 %) and elemene-type sesquiterpenes, epi-isoshyobunone (3.3-7.3 %) and shyobunone (1.5-4.6 %) were detected among the major volatile constituents in the rhizomes. The monoterpenes were represented by camphor (7.5-13.9 %) and camphene (6.1-7.7 %). In the leaf, myrcene (0.3-7.1 %), limonene (1.0-5.6 %), (Z)-beta-ocimene (2.9-6.1 %) were among the major constituents. Qualitative difference of the volatiles composition in the rhizomes and leaves are discussed as well as of the volatiles obtained by HD and MSD-SPME techniques are discussed. Biological activity tests resulted in moderate anti-acetylcholinesterase effect and significant cupric reducing antioxidant potential of the leaf oil, while the rhizome oil demonstrated relatively lower effects

Chemical and Biological Diversity of the Leaf and Rhizome Volatiles of Acorus calamus L. from Turkey

Two different isolation techniques, conventional hydrodistillation (HD) and micro-steam distillation-solid-phase microextraction (MSD-SPME), have been used to analyze the volatile constituents from the leaves and rhizomes of Acorus calamus L. by gas chromatography (GC-FID) and gas chromatography coupled to mass spectrometry (GC-MS). In all the samples studied, phenylpropanoids (16.9-35.3 %) predominated by beta-asarone (15.3-16.3 % in rhizomes, 23.4-31.7 % in leaves) were the main constituent. In addition to phenylpropanoids, the acorane type sesquiterpene acorenone B (7.4-16.4 %) and elemene-type sesquiterpenes, epi-isoshyobunone (3.3-7.3 %) and shyobunone (1.5-4.6 %) were detected among the major volatile constituents in the rhizomes. The monoterpenes were represented by camphor (7.5-13.9 %) and camphene (6.1-7.7 %). In the leaf, myrcene (0.3-7.1 %), limonene (1.0-5.6 %), (Z)-beta-ocimene (2.9-6.1 %) were among the major constituents. Qualitative difference of the volatiles composition in the rhizomes and leaves are discussed as well as of the volatiles obtained by HD and MSD-SPME techniques are discussed. Biological activity tests resulted in moderate anti-acetylcholinesterase effect and significant cupric reducing antioxidant potential of the leaf oil, while the rhizome oil demonstrated relatively lower effects

The Mutation of CD27 Deficiency Presented With Familial Hodgkin Lymphoma and a Review of the Literature

This study aimed to report 4 siblings with CD27 deficiency presented with Hodgkin lymphoma. The father of the family, his 2 wives, and 17 children born from these wives were included into the study. CD27 mutation of all the family members with, and without Hodgkin lymphoma were studied. The variants detected by the exome sequencing analysis were verified by Sanger sequencing and analyzed using SeqScape Software 3. It was determined that both the father of the family and his 2 wives carried the same variant heterozygously. Of the children born to the first mother, 2 children were normal, 3 were heterozygous and 5 were homozygous. Four of these 5 homozygous children were diagnosed with Hodgkin lymphoma. Of the children born to the second mother, 1 child was normal, 3 children were heterozygous and 2 children were homozygous, and none of them had developed a malignant event. We also showed that CD27 deficiency may enhance Treg differentiation. According to our information, this study augmented the relationship of Hodgkin lymphoma and CD27 deficiency. The detection of homozygous CD27 variant in all siblings who developed lymphoma strengthened the place of this mutation in the etiology of Hodgkin lymphoma. In contrast, the presence of homozygous siblings with no malignant event suggested the possible contributions of environmental factors on the etiology

Phytochemicals, antioxidant, and antityrosinase activities of <i>Achillea sivasica</i> Çelik and Akpulat

<p>The present study is the first report on essential oil (EO) composition, phytochemicals, and biological potential of <i>Achillea sivasica</i> tested against free radicals, oxidative damage, and tyrosinase enzyme. Gas-Chromatography Flame Ionization Detector (GC-FID) and gas chromatography/mass spectrometry (GC/MS) analyses revealed that β-pinene (11.5%, 9.3%, and 6.7%), β-pinene (7.0%, 3.0%, and 6.9%), 1,8-cineole (18.0%, 22.1%, and 6.7%), and camphor (7.6%, 4.1%, and 9.0%) were the major constituents in the EOs from the herb, flower, and leaves, respectively. Liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analysis of the extracts revealed the presence of caffeoylquinic acid derivatives, luteolin, apigenin, patuletin, isorhamnetin, cirsimaritin, and santin. The leaf extracts demonstrated strongest free radical scavenging, cupric reducing, lipid peroxidation inhibition, and antityrosinase activities.</p

Burden of Chronic Low Back Pain in the Turkish Population

WOS: 000353480500011Objective: Chronic low back pain (CLBP) is a great economic burden to the society mainly in terms of the large number of the lost work days and disability, and it appears to be growing. The economic burden of LBP in Turkey is not known. This study aims to analyze the health care resource use, work and productivity loss, and health-related economics of CLBP in Turkey. Material and Methods: The study was designed as a multi-centered cross-sectional survey of patients in physical therapy and rehabilitation clinics from eight different regions of Turkey and 662 patients with CLBP over 18 years of age were included. Data on patient sociodemographics, disease-related healthcare resource use during the previous 6 months, inability to work during the last 3 months, Roland Morris Disability Index for the functional status, and psychological health with Beck Depression Scale were collected. Direct costs included medical visits, investigations, medications, hospitalizations, orthopedic aids, and physical therapy. Indirect costs were evaluated mostly with productivity loss. Results: The total annual direct costs for CLBP per patient were estimated at 1080 TL. The indirect costs were estimated at 5511 TL per patient. Direct cost was correlated with disease severity, duration, and age. Indirect cost was higher in women. Conclusion: The indirect costs for CLBP were significantly higher than the direct costs

IL-15 negatively regulates curdlan-induced IL-23 production by human monocyte-derived dendritic cells and subsequent Th17 response

OBJECTIVE: In this study, we aimed to assess the effects of long- and short-term IL-15 cytokine exposure of human monocyte-derived curdlan-matured dendritic cells (DCs) on the production of Th17 cell-polarizing cytokine IL-23 and subsequent Th17 cell activation