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

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

Burden of Chronic Low Back Pain in the Turkish Population

Objective: 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

Characterization of cord blood CD3(+)TCRV alpha 7.2(+)CD161(high) T and innate lymphoid cells in the pregnancies with gestational diabetes, morbidly adherent placenta, and pregnancy hypertension diseases

Problem Although pregnant women with gestational diabetes (GD), morbidly adherent placenta (MAP), and pregnancy hypertension (pHT) diseases lead to intrauterine growth restriction (IUGR), little is known about their effect on mucosal-associated invariant T (MAIT) and innate lymphoid cells (ILC) in the umbilical cord. This study aimed to quantify and characterize MAIT cells and ILCs in the cord blood of pregnant women with GD, MAP, and pHT diseases. Method of study Cord blood mononuclear cells (CBMCs) were isolated by Ficoll-Paque gradient. CD3(+)TCRV alpha 7.2(+)CD161(high) cells and ILC subsets were quantified by flow cytometry. CBMCs were stimulated with PMA/Ionomycin and Golgi Plug for 4 h and stained for IFN-gamma, TNF-alpha, and granzyme B. The stained cells were analyzed on FACS ARIA III. Results Compared with healthy pregnancies, in the cord blood of the pHT group, elevated number of lymphocytes was observed. Moreover, the absolute number of IFN-gamma producing CD4(+) or CD4(-) subsets of CD3(+)TCRV alpha 7.2(+)CD161(high) cells as well as those producing granzyme B were significantly elevated in the pHT group compared to healthy controls suggesting increased MAIT cell activity in the pHT cord blood. Similarly, in the MAP group, the absolute number of total CD3(+)TCRV alpha 7.2(+)CD161(high) cells, but not individual CD4(+) or negative subsets, were significantly increased compared with healthy controls' cord blood. Absolute numbers of total CD3(+)TCRV alpha 7.2(+)CD161(high) cells and their subsets were comparable in the cord blood of the GD group compared with healthy controls. Finally, the absolute number of total ILCs and ILC3 subset were significantly elevated in only pHT cord blood compared with healthy controls. Our data also reveal that IFN-gamma(+) or granzyme B+ cell numbers negatively correlated with fetal birth weight. Conclusions CD3(+)TCRV alpha 7.2(+)CD161(high) cells and ILCs show unique expansion and activity in the cord blood of pregnant women with distinct diseases causing IUGR and may play roles in fetal growth restriction