Search results for: interleukin%20-10
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1096

Search results for: interleukin%20-10

1066 Suppression of Immunostimulatory Function of Dendritic Cells and Prolongation of Skin Allograft Survival by Dryocrassin

Authors: Hsin-Lien Lin, Ju-Hui Fu

Abstract:

Dendritic cells (DCs) are the major professional antigen-presenting cells for the development of optimal T-cell immunity. DCs can be used as pharmacological targets to screen novel biological modifiers for the treatment of harmful immune responses, such as transplantation rejection. Dryopteris crassirhizoma Nakai (Aspiadaceae) is used for traditional herbal medicine in the region of East Asia. The root of this fern plant has been listed for treating inflammatory diseases. Dryocrassin is the tetrameric phlorophenone component derived from Dryopteris. Here, we tested the immunomodulatory potential of dryocrassin on lipopolysaccharide (LPS)-stimulated activation of mouse bone marrow-derived DCs in vitro and in skin allograft transplantation in vivo. Results demonstrated that dryocrassin reduced the secretion of tumor necrosis factor-α, interleukin-6, and interleukin-12p70 by LPS-stimulated DCs. The expression of LPS-induced major histocompatibility complex class II, CD40, and CD86 on DCs was also blocked by dryocrassin. Moreover, LPS-stimulated DC-elicited allogeneic T-cell proliferation was lessened by dryocrassin. In addition, dryocrassin inhibited LPS-induced activation of IϰB kinase, JNK/p38 mitogen-activated protein kinase, as well as the translocation of NF-ϰB. Treatment with dryocrassin obviously diminished 2,4-dinitro-1-fluorobenzene- induced delayed-type hypersensitivity and prolonged skin allograft survival. Dryocrassin may be one of the potent immunosuppressive agents for transplant rejection through the destruction of DC maturation and function.

Keywords: dryocrassin, dendritic cells, immunosuppression, skin allograft

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1065 Seismotectonics of Southern Haiti: A Faulting Model for the 12 January 2010 M7 Earthquake

Authors: Newdeskarl Saint Fleur, Nathalie Feuillet, Raphaël Grandin, Éric Jacques, Jennifer Weil-Accardo, Yann Klinger

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The prevailing consensus is that the 2010 Mw7.0 Haiti earthquake left the Enriquillo–Plantain Garden strike-slip Fault (EPGF) unruptured but broke unmapped blind north-dipping thrusts. Using high-resolution topography, aerial images, bathymetry and geology we identified previously unrecognized south-dipping NW-SE-striking active thrusts in southern Haiti. One of them, Lamentin thrust (LT), cuts across the crowded city of Carrefour, extends offshore into Port-au-Prince Bay and connects at depth with the EPGF. We propose that both faults broke in 2010. The rupture likely initiated on the thrust and propagated further along the EPGF due to unclamping. This scenario is consistent with geodetic, seismological and field data. The 2010 earthquake increased the stress toward failure on the unruptured segments of the EPGF and on neighboring thrusts, significantly increasing the seismic hazard in the Port-au-Prince urban area. The numerous active thrusts recognized in that area must be considered for future evaluation of the seismic hazard.

Keywords: active faulting, enriquillo-plantain garden fault, Haiti earthquake, seismic hazard

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1064 Financial Ethics: A Review of 2010 Flash Crash

Authors: Omer Farooq, Salman Ahmed Khan, Sadaf Khalid

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Modern day stock markets have almost entirely became automated. Even though it means increased profits for the investors by algorithms acting upon the slightest price change in order of microseconds, it also has given birth to many ethical dilemmas in the sense that slightest mistake can cause people to lose all of their livelihoods. This paper reviews one such event that happened on May 06, 2010 in which $1 trillion dollars disappeared from the Dow Jones Industrial Average. We are going to discuss its various aspects and the ethical dilemmas that have arisen due to it.

Keywords: flash crash, market crash, stock market, stock market crash

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1063 Role of Interleukin 6 on Cell Differentiations in Stem Cells Isolated from Human Exfoliated Deciduous Teeth

Authors: Nunthawan Nowwarote, Waleerat Sukarawan, Prasit Pavasant, Thanaphum Osathanon

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Interleukin 6 (IL-6) is a multifunctional cytokine, regulating various biological responses in several tissues. A Recent study shows that IL-6 plays a role in stemness maintenance in stem cells isolated from human exfoliated deciduous teeth (SHEDs). However, the role of IL-6 on cell differentiation in SHEDs remains unknown. The present study investigated the effect of IL-6 on SHEDs differentiation. Cells were isolated from dental pulp tissues of human deciduous teeth. Flow cytometry was used to determined mesenchymal stem cell marker expression, and the multipotential differentiation (osteogenic, adipogenic and neurogenic lineage ) was also determined. The mRNA was determined using real-time quantitative polymerase chain reaction, and the phenotypes were confirmed by chemical and immunofluorescence staining. Results demonstrated that SHEDs expressed CD44, CD73, CD90, CD105 but not CD45. Further, the up-regulation of osteogenic, adipogenic and neurogenic marker genes was observed upon maintaining cells in osteogenic, adipogenic and neurogenic induction medium, respectively. The addition of IL-6 induced osteogenic by up-regulated osteogenic marker gene also increased in vitro mineralization. Under neurogenic medium supplement with IL-6, up-regulated neurogenic marker. Whereas, an addition of IL-6 attenuated adipogenic differentiation by SHEDs. In conclusion, this evidence implies that IL-6 may participate in cells differentiation ability of SHEDs.

Keywords: SHEDs, IL-6, cell differentiations, dental pulp

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1062 Establishment of Air Quality Zones in Italy

Authors: M. G. Dirodi, G. Gugliotta, C. Leonardi

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The member states shall establish zones and agglomerations throughout their territory to assess and manage air quality in order to comply with European directives. In Italy decree 155/2010, transposing Directive 2008/50/EC on ambient air quality and cleaner air for Europe, merged into a single act the previous provisions on ambient air quality assessment and management, including those resulting from the implementation of Directive 2004/107/EC relating to arsenic, cadmium, nickel, mercury, and polycyclic aromatic hydrocarbons in ambient air. Decree 155/2010 introduced stricter rules for identifying zones on the basis of the characteristics of the territory in spite of considering pollution levels, as it was in the past. The implementation of such new criteria has reduced the great variability of the previous zoning, leading to a significant reduction of the total number of zones and to a complete and uniform ambient air quality assessment and management throughout the Country. The present document is related to the new zones definition in Italy according to Decree 155/2010. In particular, the paper contains the description and the analysis of the outcome of zoning and classification.

Keywords: zones, agglomerations, air quality assessment, classification

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1061 Quantifying the Rapid Urbanization Impact on Potential Stormwater Runoff of Dhaka City, Bangladesh

Authors: Md. Kumruzzaman, Anutosh Das, Md. Mosharraf Hossain

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Historically, rapid urban growth activities are considered one of the main culprits behind urban floods or waterlogging. The increased unplanned urbanization of many areas of Dhaka has resulted in waterlogging, urban floods, and increasing groundwater depth. To determine potential groundwater recharge from precipitation, the study is being conducted to examine the changes in land use/land cover (LULC) and urban runoff extent based on the NRCS-CN from 2005–2021. Four kinds of land use are used to examine the LULC change: built-up, bare land, vegetation, and water body. These categories are used for the years 2005, 2010, 2015, and 2021. The built-up area is growing at a relatively fast rate: 7.43%, 17.4%, and 5.21%, respectively, between the years 2005 and 2010, 2010 and 2015, and 2015 and 2021. As the amount of impervious surface rose in Dhaka city, stormwater discharge increased from 2005 to 2021. In 2005, 2010, 2015, and 2021, heavy stormwater runoff regions made up around 24.873%, 32.616%, 49.118%, and 55.986% of the entire Dhaka city. Stormwater runoff accounted for around 53.738%, 55.092%, 63.472%, and 67.061% of the total rainfall in 2005, 2010, 2015, and 2021, respectively. Between 2005 and 2021, a significant portion of the natural land cover was altered because of the expanding impervious surface, which also harmed the natural drainage system. Due to careless growth, the potential for stormwater runoff and groundwater recharge in Dhaka city worsens every year. Concerning this situation, a sustainable urban drainage system (SUDS) can be the best possible solution for minimizing the stormwater runoff and groundwater recharge problem.

Keywords: LULC, impervious surface, stormwater runoff, groundwater recharge, SUDS

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1060 In vitro Study of Inflammatory Gene Expression Suppression of Strawberry and Blackberry Extracts

Authors: Franco Van De Velde, Debora Esposito, Maria E. Pirovani, Mary A. Lila

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The physiology of various inflammatory diseases is a complex process mediated by inflammatory and immune cells such as macrophages and monocytes. Chronic inflammation, as observed in many cardiovascular and autoimmune disorders, occurs when the low-grade inflammatory response fails to resolve with time. Because of the complexity of the chronic inflammatory disease, major efforts have focused on identifying novel anti-inflammatory agents and dietary regimes that prevent the pro-inflammatory process at the early stage of gene expression of key pro-inflammatory mediators and cytokines. The ability of the extracts of three blackberry cultivars (‘Jumbo’, ‘Black Satin’ and ‘Dirksen’), and one strawberry cultivar (‘Camarosa’) to inhibit four well-known genetic biomarkers of inflammation: inducible nitric oxide synthase (iNOS), cyclooxynase-2 (Cox-2), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in an in vitro lipopolysaccharide-stimulated murine RAW 264.7 macrophage model were investigated. Moreover, the effect of latter extracts on the intracellular reactive oxygen species (ROS) and nitric oxide (NO) production was assessed. Assay was conducted with 50 µg/mL crude extract concentration, an amount that is easily achievable in the gastrointestinal tract after berries consumption. The mRNA expression levels of Cox-2 and IL-6 were reduced consistently (more than 30%) by extracts of ‘Jumbo’ and ‘Black Satin’ blackberries. Strawberry extracts showed high reduction in mRNA expression levels of IL-6 (more than 65%) and exhibited moderate reduction in mRNA expression of Cox-2 (more than 35%). The latter behavior mirrors the intracellular ROS production of the LPS stimulated RAW 264.7 macrophages after the treatment with blackberry ‘Black Satin’ and ‘Jumbo’, and strawberry ‘Camarosa’ extracts, suggesting that phytochemicals from these fruits may play a role in the health maintenance by reducing oxidative stress. On the other hand, effective inhibition in the gene expression of IL-1β and iNOS was not observed by any of blackberry and strawberry extracts. However, suppression in the NO production in the activated macrophages among 5–25% was observed by ‘Jumbo’ and ‘Black Satin’ blackberry extracts and ‘Camarosa’ strawberry extracts, suggesting a higher NO suppression property by phytochemicals of these fruits. All these results suggest the potential beneficial effects of studied berries as functional foods with antioxidant and anti-inflammatory roles. Moreover, the underlying role of phytochemicals from these fruits in the protection of inflammatory process will deserve to be further explored.

Keywords: cyclooxygenase-2, functional foods, interleukin-6, reactive oxygen species

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1059 Antioxidant Effects of C-Phycocyanin on Oxidized Astrocyte in Brain Injury Using 2D and 3D Neural Nanofiber Tissue Model

Authors: Seung Ju Yeon, Seul Ki Min, Jun Sang Park, Yeo Seon Kwon, Hoo Cheol Lee, Hyun Jung Shim, Il-Doo Kim, Ja Kyeong Lee, Hwa Sung Shin

Abstract:

In brain injury, depleting oxidative stress is the most effective way to reduce the brain infarct size. C-phycocyanin (C-Pc) is a well-known antioxidant protein that has neuroprotective effects obtained from green microalgae. Astrocyte is glial cell that supports the nerve cell such as neuron, which account for a large portion of the brain. In brain injury, such as ischemia and reperfusion, astrocyte has an important rule that overcomes the oxidative stress and protect from brain reactive oxygen species (ROS) injury. However little is known about how C-Pc regulates the anti-oxidants effects of astrocyte. In this study, when the C-Pc was treated in oxidized astrocyte, we confirmed that inflammatory factors Interleukin-6 and Interleukin-3 were increased and antioxidants enzyme, Superoxide dismutase (SOD) and catalase was upregulated, and neurotrophic factors, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) was alleviated. Also, it was confirmed to reduce infarct size of the brain in ischemia and reperfusion because C-Pc has anti-oxidant effects in middle cerebral artery occlusion (MCAO) animal model. These results show that C-Pc can help astrocytes lead neuroprotective activities in the oxidative stressed environment of the brain. In summary, the C-PC protects astrocytes from oxidative stress and has anti-oxidative, anti-inflammatory, neurotrophic effects under ischemic situations.

Keywords: c-phycocyanin, astrocyte, reactive oxygen species, ischemia and reperfusion, neuroprotective effect

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1058 Endeavor to Develop Immunological and Hematological Early Diagnostic Marker to Check the Conversion of Asymptomatic to Symptomatic Visceral Leishmaniasis

Authors: Roshan Kamal Topno, Maneesh Kumar, Manas Ranjan Dikhit, Krishna Pandey, Major Madhukar, Vidhya Nand Rabidas, Vahab Ali, Ganesh Chandra Sahoo, Bhawana, Devendra Prasad Yadav, Rishikesh Kumar, Pradeep Das

Abstract:

A diagnostic marker for asymptomatic subject becomes a crucial need for advocating early prophylactic majors to control protozoal infection. The main issue in epidemiological affected regions is the presence of an asymptomatic individual that might potentially convert to a symptomatic visceral leishmaniasis (VL). The epidemiological study has been conducted at highly VL endemic Moriyama village in Patna district, Bihar, India that covers total population of 1540 individuals. Here, 1104(74.02%) people had been randomly screened and only 46 (4.17%) asymptomatic individuals were found sero-positive by the rK39 test. After taking signed informed consent form, blood samples were collected from 46 asymptomatic subjects for further hematological and immunological tests. Total leukocyte count, hemoglobin (gm%), neutrophil, lymphocyte, platelet count and interleukin-10 (IL-10) had been included as diagnostic markers. Interestingly only 5 (10.86%) individuals showed their asymptomatic conversion into symptomatic VL patients during quarterly surveillance. In overall analysis only two markers are suggestive for disease conversion that is hemoglobin (gm%) and IL-10. In all the infected patients, both the mean decrease in hemoglobin and mean increase of IL-10 was 19.23% from its normal value. The results might suggest that hematological and immunological changes would become helpful for early diagnosis of asymptomatic to symptomatic VL conversion.

Keywords: asymptomatic, epidemiological, symptomatic visceral leishmaniasis, hemoglobin (gm%), interleukin-10, diagnosis

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1057 Protective Effects of Genistein against Cyclophosphamide-Induced Hepatotoxicity in Rats: Involvement of Anti-Inflammatory and Anti-Oxidant Activities

Authors: Dina F. Mansour, Dalia O. Saleh, Rasha E. Mostafa

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Cyclophosphamide (CP), the most commonly used chemotherapeutic agent, was reported to cause many side effects including urotoxicity, cardiotoxicity, gonadotoxicity, and hepatotoxicity; this limits its clinical practice. In the present study, the protective effect of genistein (GEN), the major phytoestrogen in soy products that possesses various pharmacological activities, has been investigated against CP-induced acute liver damage in rats. Forty adult Sprague-Dawley rats were allocated into five groups. The first group received the vehicles and act as normal control. In the other groups, rats were injected with a single dose of CP (200 mg/kg, i.p). The last three groups were pretreated with subcutaneous GEN at doses of 0.5, 1 and 2 mg/kg/day, respectively, for 15 consecutive days prior CP injection. Forty-eight hours following CP injection, rats of all groups were investigated for the serum levels of alanine transaminase and aspartate transaminase, as well as the liver contents of reduced glutathione, malondialdehyde, nitrite, interleukin-1β, and myeloperoxidase. Histopathological examination of liver tissues was also conducted. CP resulted in acute liver damage in rats as evidenced by alteration of liver function biomarkers, oxidative stress, and inflammatory markers; that was confirmed by the histopathological outcomes. Pretreatment of rats with GEN significantly protected against CP-induced deterioration of liver function and showed marked anti-oxidant and anti-inflammatory properties that were demonstrated by the biochemical and histopathological findings. In conclusion, the present findings demonstrated the protective effects of GEN against CP-induced liver damage and suggested role of its antioxidant and anti-inflammatory activities.

Keywords: cyclophosphamide, genistein, inflammation, interleukin-1β, liver, myeloperoxidase, oxidative stress

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1056 Genetics of Atopic Dermatitis: Role of Cytokines Genes Polymorphisms

Authors: Ghaleb Bin Huraib, Fahad Al Harthi, Misbahul Arfin, Abdulrahman Al-Asmari

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Atopic dermatitis (AD), also known as atopic eczema, is a chronic inflammatory skin disease characterized by severe itching and recurrent relapsing eczema-like skin lesions, affecting up to 20% of children and 10% of adults in industrialized countries. AD is a complex multifactorial disease, and its exact etiology and pathogenesis have not been fully elucidated. The aim of this study was to investigate the impact of gene polymorphisms of T helper cell subtype Th1 and Th2 cytokines, interferon-gamma (IFN-γ), interleukin-6 (IL-6) and transforming growth factor (TGF)-β1on AD susceptibility in a Saudi cohort. One hundred four unrelated patients with AD and 195 healthy controls were genotyped for IFN-γ (874A/T), IL-6 (174G/C) and TGF-β1 (509C/T) polymorphisms using ARMS-PCR and PCR-RFLP technique. The frequency of genotypes AA and AT of IFN-γ (874A/T) differed significantly among patients and controls (P 0.001). The genotype AT was increased while genotype AA was decreased in AD patients as compared to controls. AD patients also had higher frequency of T containing genotypes (AT+TT) than controls (P = 0.001). The frequencies of allele T and A were statistically different in patients and controls (P = 0.04). The frequencies of genotype GG and allele G of IL-6 (174G/C) were significantly higher while genotype GC and allele C were lower in AD patients than controls. There was no significant difference in the frequencies of alleles and genotypes of TGF-β1 (509C/T) polymorphism between patient and control groups. These results showed that susceptibility to AD is influenced by presence or absence of genotypes of IFN-γ (874A/T) and IL-6 (174G/C) polymorphisms. It is concluded that T-allele and T-containing genotypes (AT+TT) of IFN-γ (874A/T) and G-allele and GG genotype ofIL-6 (174G/C) polymorphisms are susceptible to AD in Saudis.On the other hand, the TGF-β1 (509C/T) polymorphism may not be associated with AD risk in Saudi population however further studies with large sample size are required to confirm these findings.

Keywords: atopic dermatitis, interferon-γ, interleukin-6, transforming growth factor-β1, polymorphism

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1055 Climate Change and the Role of Foreign-Invested Enterprises

Authors: Xuemei Jiang, Kunfu Zhu, Shouyang Wang

Abstract:

In this paper, we selected China as a case and employ a time-series of unique input-output tables distinguishing firm ownership and processing exports, to evaluate the role of foreign-invested enterprises (FIEs) in China’s rapid carbon dioxide emission growth. The results suggested that FIEs contributed to 11.55% of the economic outputs’ growth in China between 1992-2010, but accounted for only 9.65% of the growth of carbon dioxide emissions. In relative term, until 2010 FIEs still emitted much less than Chinese-owned enterprises (COEs) when producing the same amount of outputs, although COEs experienced much faster technology upgrades. In an ideal scenario where we assume the final demands remain unchanged and COEs completely mirror the advanced technologies of FIEs, more than 2000 Mt of carbon dioxide emissions would be reduced for China in 2010. From a policy perspective, the widespread FIEs are very effective and efficient channel to encourage technology transfer from developed to developing countries.

Keywords: carbon dioxide emissions, foreign-invested enterprises, technology transfer, input–output analysis, China

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1054 Increased Cytolytic Activity of Effector T-Cells against Cholangiocarcinoma Cells by Self-Differentiated Dendritic Cells with Down-Regulation of Interleukin-10 and Transforming Growth Factor-β Receptors

Authors: Chutamas Thepmalee, Aussara Panya, Mutita Junking, Jatuporn Sujjitjoon, Nunghathai Sawasdee, Pa-Thai Yenchitsomanus

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Cholangiocarcinoma (CCA) is an aggressive malignancy of bile duct epithelial cells in which the standard treatments, including surgery, radiotherapy, chemotherapy, and targeted therapy are partially effective. Many solid tumors including CCA escape host immune responses by creating tumor microenvironment and generating immunosuppressive cytokines such as interleukin-10 (IL-10) and transforming growth factor-β (TGF-β). These cytokines can inhibit dendritic cell (DC) differentiation and function, leading to decreased activation and response of effector CD4+ and CD8+ T cells for cancer cell elimination. To overcome the effects of these immunosuppressive cytokines and to increase ability of DC to activate effector CD4+ and CD8+ T cells, we generated self-differentiated DCs (SD-DCs) with down-regulation of IL-10 and TGF-β receptors for activation of effector CD4+ and CD8+ T cells. Human peripheral blood monocytes were initially transduced with lentiviral particles containing the genes encoding GM-CSF and IL-4 and then secondly transduced with lentiviral particles containing short-hairpin RNAs (shRNAs) to knock-down mRNAs of IL-10 and TGF-β receptors. The generated SD-DCs showed up-regulation of MHC class II (HLA-DR) and co-stimulatory molecules (CD40 and CD86), comparable to those of DCs generated by convention method. Suppression of IL-10 and TGF-β receptors on SD-DCs by specific shRNAs significantly increased levels of IFN-γ and also increased cytolytic activity of DC-activated effector T cells against CCA cell lines (KKU-213 and KKU-100), but it had little effect to immortalized cholangiocytes (MMNK-1). Thus, SD-DCs with down-regulation of IL-10 and TGF-β receptors increased activation of effector T cells, which is a recommended method to improve DC function for the preparation of DC-activated effector T cells for adoptive T-cell therapy.

Keywords: cholangiocarcinoma, IL-10 receptor, self-differentiated dendritic cells, TGF-β receptor

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1053 Innovativeness of the Furniture Enterprises in Bulgaria

Authors: Radostina Popova

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The paper presents an analysis of the innovation performance of small and medium-sized furniture enterprises in Bulgaria, accounting for over 97% of the companies in the sector. It contains advanced features of innovation in enterprises, specific features of the furniture industry in Bulgaria and analysis of the results of studies on the topic. The results from studies of three successive periods - 2006-2008; 2008-2010; 2010-2012, during which were studied 594 small and medium-sized furniture enterprises. There are commonly used in the EU definitions and indicators (European Commission, OECD, Oslo Manual), which allows for the comparability of results.

Keywords: innovation activity, competitiveness of innovation, furniture enterprises in Bulgaria

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1052 The Behavior of O3 and Its Nitrogen and Sulfur Precursors in Sea Breeze Scenarios on the Coast of Gabès (Tunisia)

Authors: Allagui Mohamed

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The study of the concentrations of atmospheric pollutants is analyzed during two days of sea breeze (April 26, 2010, and January 11, 2008) on the Mediterranean coasts, just in front of Gabès (33 ° 53 'N, 10 ° 07' E), Tunisia. During these two cases, we found that Gabès was contaminated by a coastal sea breeze. On April 26, 2010, the terrestrial synoptic wind admitted a maximum speed of about 6 m / s and was approximately perpendicular to the coast and making the breeze easier. On January 11, 2008, the terrestrial wind was local. Under these conditions, O3 and, therefore, the concentrations were multiplied by the factors 0.1 and 2, respectively. The episodes of ozone concentrations faithfully follow the sea breeze circulation. These sea breeze events can be responsible for high concentrations of NO, NO2, and SO2 as air pollutants in this area.

Keywords: sea breeze, O3, cost town, air quality

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1051 The Constitution of Kenya, 2010, and the Feminist Legal Theory

Authors: Tecla Rita Karendi, Andy Cons Matata

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Although before and at the advent of colonial administration, several women such as Mekatilili wa Menza and Muthoni Nyanjiru took up leadership positions in resisting the colonial administration. Kenya is generally considered a patriarchal society. Many women who tried to take up positions of leadership in postcolonial Kenya, such as the Nobel Prize winner Wangari Maathai, were branded as prostitutes or generally immoral women. However, the Constitution of Kenya, 2010, has since made a huge impact not only in the area of affirmative action but also in various aspects of the feminist legal theory such as the constitutional requirement that no more than two-thirds of the members of the elective or appointive bodies should be of the same gender. This favours women who are often sidelined in elective posts such as parliament or county assemblies and state-appointed posts in the parastatals and commissions. The constitution also recognizes the right to abortion, which was outrightly outlawed in the independence constitution. Certain practices adverse to women’s health, such as wife inheritance, female genital mutilation, and property rights, are either outlawed or framed to recognized women’s rights. The education of the girl-child is also now considered a priority, unlike in the past. Despite these developments, a lot remains to be done.

Keywords: feminist legal theory, constitution of Kenya, 2010, affirmative action, leadership

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1050 In vitro Modulation of Cytokine Expression by an Aqueous Licorice Extract in Canine

Authors: A. Watson, G. Telford, D. I. Pritchard

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Objective: We investigated the immunomodulatory ability of licorice (Glycyrrhiza glabra). Such activities could have value for the management of common immunological diseases in dogs, such as environmental allergy. This study investigated the potential of a Licorice root extract (LRE) to influence the relative expression of Th-1, Th-2, and Th-17 cytokines in canine peripheral blood mononuclear cells (PBMC). Methods: A LRE was prepared using an alcoholic-aqueous-based solvent method. The extract was tested in three in vitro assays using canine leukocytes to determine its toxicity and immunoregulatory profile. Extract toxicity was assessed using the human T-lymphocyte cell line, Jurkat E6.1. The impact of the extract on the proliferation of concanavalin-activated canine PBMC was also determined. Finally, the extract was assessed for its ability to influence cytokine release in activated PBMC, measuring culture medium concentrations of interleukin-17, interferon gamma, and interleukin-4. One-way ANOVA followed by Dunnett’s post-test was used for statistics using concanavalin positive control as reference (p ≤ 0.05). Results: There was evidence that the LRE had specific immunomodulatory properties, causing significant inhibition of IL4 expression over a non-toxic/non-cytostatic concentration range (p < 0.001). In the same cell incubations, there was no significant impact on IL17 nor IFNg over the same non-toxic/non-cytostatic concentration range. Conclusion: The study provides in vitro evidence that LRE preferentially reduces the expression of a Th-2-type cytokine, IL4. The dog population, as with humans, is prone to conditions associated with a Th-2 bias of the immune system, such as environmental allergy. Based on these results, licorice merits further evaluation as a useful immune modulator for such allergic diseases.

Keywords: cytokine, Glycyrrhiza glabra, peripheral blood mononuclear cells, T-cell activation

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1049 Angiogenic and Immunomodulatory Properties and Phenotype of Mesenchymal Stromal Cells Can Be Regulated by Cytokine Treatment

Authors: Ekaterina Zubkova, Irina Beloglazova, Iurii Stafeev, Konsyantin Dergilev, Yelena Parfyonova, Mikhail Menshikov

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Mesenchymal stromal cells from adipose tissue (MSC) currently are widely used in regenerative medicine to restore the function of damaged tissues, but that is significantly hampered by their heterogeneity. One of the modern approaches to overcoming this obstacle is the polarization of cell subpopulations into a specific phenotype under the influence of cytokines and other factors that activate receptors and signal transmission to cells. We polarized MSC with factors affecting the inflammatory signaling and functional properties of cells, followed by verification of their expression profile and ability to affect the polarization of macrophages. RT-PCR evaluation showed that cells treated with LPS, interleukin-17, tumor necrosis factor α (TNF α), primarily express pro-inflammatory factors and cytokines, and after treatment with polyninosin polycytidic acid and interleukin-4 (IL4) anti-inflammatory factors and some proinflammatory factors. MSC polarized with pro-inflammatory cytokines showed a more robust pro-angiogenic effect in fibrin gel bead 3D angiogenesis assay. Further, we evaluated the possibility of paracrine effects of MSCs on the polarization of intact macrophages. Polarization efficiency was assesed by expression of M1/M2 phenotype markers CD80 and CD206. We showed that conditioned media from MSC preincubated in the presence of IL-4 cause an increase in CD206 expression similar to that observed in M2 macrophages. Conditioned media from MSC polarized in the presence of LPS or TNF-α increased the expression of CD80 antigen in macrophages, similar to that observed in M1 macrophages. In other cases, a pronounced paracrine effect of MSC on the polarization of macrophages was not detected. Thus, our study showed that the polarization of MSC along the pro-inflammatory or anti-inflammatory pathway allows us to obtain cell subpopulations that have a multidirectional modulating effect on the polarization of macrophages. (RFBR grants 20-015-00405 and 18-015-00398.)

Keywords: angiogenesis, cytokines, mesenchymal, polarization, inflammation

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1048 The Role of Data Protection Officer in Managing Individual Data: Issues and Challenges

Authors: Nazura Abdul Manap, Siti Nur Farah Atiqah Salleh

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For decades, the misuse of personal data has been a critical issue. Malaysia has accepted responsibility by implementing the Malaysian Personal Data Protection Act 2010 to secure personal data (PDPA 2010). After more than a decade, this legislation is set to be revised by the current PDPA 2023 Amendment Bill to align with the world's key personal data protection regulations, such as the European Union General Data Protection Regulations (GDPR). Among the other suggested adjustments is the Data User's appointment of a Data Protection Officer (DPO) to ensure the commercial entity's compliance with the PDPA 2010 criteria. The change is expected to be enacted in parliament fairly soon; nevertheless, based on the experience of the Personal Data Protection Department (PDPD) in implementing the Act, it is projected that there will be a slew of additional concerns associated with the DPO mandate. Consequently, the goal of this article is to highlight the issues that the DPO will encounter and how the Personal Data Protection Department should respond to this subject. The study result was produced using a qualitative technique based on an examination of the current literature. This research reveals that there are probable obstacles experienced by the DPO, and thus, there should be a definite, clear guideline in place to aid DPO in executing their tasks. It is argued that appointing a DPO is a wise measure in ensuring that the legal data security requirements are met.

Keywords: guideline, law, data protection officer, personal data

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1047 Status of Communication and Swallowing Therapy in Patient with a Tracheostomy

Authors: Ya-Hui Wang

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Lower speech therapy rate of tracheostomized patient was noted in comparison with previous researches. This study is aim to shed light on the referral status of speech therapy in those patients in Taiwan. This study developed an analysis for the size and key characteristics of the population of tracheostomized in-patient in the Taiwan. Method: We analyzed National Healthcare Insurance data (The Collaboration Center of Health Information Application, CCHIA) from Jan 1 2010 to Dec 31 2010. Result: over ages 3, number of tracheostomized in-patient is directly proportional to age. A high service loading was observed in North region in comparison with other regions. Only 4.87% of the tracheostomized in-patients were referred for speech therapy, and 1.9% for swallow examination, 2.5% for communication evaluation.

Keywords: refer, speech therapy, training, rehabilitation

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1046 Energy Policy of India: An Assessment of Its Impacts and Way Forward

Authors: Mrinal Saurabh Bhaskar, Rahul E Ravindranathan, Priyangana Borah

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Energy plays a key role and as a driving force for economic and social growth for any country. To manage the energy sources and its efficient utilization in different economic sectors, energy policy of a country is critical. The energy performance of a country is measured in Energy Intensity and India’s Energy Intensity due to several policies interventions has reduced from 0.53 toe/1000USD (2010) in the year 2000 to 0.38 toe/1000USD (2010) in the year 2014, which is about 28 per cent reduction. The Government of India has taken several initiates to manage their increasing energy demand and meet the climate change goals defined by them. The major policy milestones in India related to energy are (i) Enactment of Energy Conservation (EC) Act 2001 (ii) Establishment of Bureau of Energy Efficiency 2001 (iii) National Action Plan on Climate Change (iv) Launch of Demand Side Management schemes (v) Amendment of EC Act 2010 (vi) Launch of Perform Achieve and Trade scheme 2012. Through a critical review, this paper highlights the key energy policy interventions by India, its benefits and impact, challenges faced and efforts of the Government to overcome such challenges. Such take away would be helpful for other countries who are proposing to prepare or amend their energy policy for their different economic sectors.

Keywords: energy, efficiency, climate, policy

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1045 Spatial Climate Changes in the Province of Macerata, Central Italy, Analyzed by GIS Software

Authors: Matteo Gentilucci, Marco Materazzi, Gilberto Pambianchi

Abstract:

Climate change is an increasingly central issue in the world, because it affects many of human activities. In this context regional studies are of great importance because they sometimes differ from the general trend. This research focuses on a small area of central Italy which overlooks the Adriatic Sea, the province of Macerata. The aim is to analyze space-based climate changes, for precipitation and temperatures, in the last 3 climatological standard normals (1961-1990; 1971-2000; 1981-2010) through GIS software. The data collected from 30 weather stations for temperature and 61 rain gauges for precipitation were subject to quality controls: validation and homogenization. These data were fundamental for the spatialization of the variables (temperature and precipitation) through geostatistical techniques. To assess the best geostatistical technique for interpolation, the results of cross correlation were used. The co-kriging method with altitude as independent variable produced the best cross validation results for all time periods, among the methods analysed, with 'root mean square error standardized' close to 1, 'mean standardized error' close to 0, 'average standard error' and 'root mean square error' with similar values. The maps resulting from the analysis were compared by subtraction between rasters, producing 3 maps of annual variation and three other maps for each month of the year (1961/1990-1971/2000; 1971/2000-1981/2010; 1961/1990-1981/2010). The results show an increase in average annual temperature of about 0.1°C between 1961-1990 and 1971-2000 and 0.6 °C between 1961-1990 and 1981-2010. Instead annual precipitation shows an opposite trend, with an average difference from 1961-1990 to 1971-2000 of about 35 mm and from 1961-1990 to 1981-2010 of about 60 mm. Furthermore, the differences in the areas have been highlighted with area graphs and summarized in several tables as descriptive analysis. In fact for temperature between 1961-1990 and 1971-2000 the most areally represented frequency is 0.08°C (77.04 Km² on a total of about 2800 km²) with a kurtosis of 3.95 and a skewness of 2.19. Instead, the differences for temperatures from 1961-1990 to 1981-2010 show a most areally represented frequency of 0.83 °C, with -0.45 as kurtosis and 0.92 as skewness (36.9 km²). Therefore it can be said that distribution is more pointed for 1961/1990-1971/2000 and smoother but more intense in the growth for 1961/1990-1981/2010. In contrast, precipitation shows a very similar shape of distribution, although with different intensities, for both variations periods (first period 1961/1990-1971/2000 and second one 1961/1990-1981/2010) with similar values of kurtosis (1st = 1.93; 2nd = 1.34), skewness (1st = 1.81; 2nd = 1.62 for the second) and area of the most represented frequency (1st = 60.72 km²; 2nd = 52.80 km²). In conclusion, this methodology of analysis allows the assessment of small scale climate change for each month of the year and could be further investigated in relation to regional atmospheric dynamics.

Keywords: climate change, GIS, interpolation, co-kriging

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1044 The Effect of High Intensity by Intervals Training on Plasma Interleukin 13 and Insulin Resistance in Patients with Attention Deficit Hyperactivity Disorder (ADHD)

Authors: Goodarzvand Fatemeh, Soori Rahman, Effatpanah Mohammad, Ajbarnejad Ali

Abstract:

Attention deficit hyperactivity disorder (ADHD) is characterized by a pervasive pattern of developmentally inappropriate inattentive, impulsive and hyperactive behaviors that typically begin during the preschool ages and often persist into adulthood. This disorder is related to autism and schizophrenia and other psychological disorders and clinical conditions such as insulin resistance and they may operate through common pathways, and treatments used exclusively for one of these conditions may prove beneficial for the others. While ADHD is not fully understood as developmental disorder with an etiopathogeny, but studies show that core symptom of disorder was associated with and increased by the interleukins IL-13, where relation of IL-13 with inattention was notable. Regular exercise improves functions associated with attention deficit hyperactivity disorder (ADHD). However, the impact of exercise on cytokines associated with the disease activity remains relatively unexplored. The aim of this study was to examine the effects of 6 weeks high intensity by intervals training (HIIT) on IL-13 levels and insulin resistance in boys with ADHD. Twenty eight boys with ADHD disease in a range of 12-18 year of old participated in this study as the subject. Subjects were divided into control group (n=10) and training group (n=18) randomly. The training group performed progressive HIIT program, 3 days a week for 6 weeks. The control group was in absolute rest at the same time. The results showed that after six weeks of HIIT, IL-13 decreased in the exercise group and these changes achieved (p= 0.002) statistical significance (p < 0.005). The results suggest HIIT with specific intensity and duration utilized in this study had not significant effect on insulin resistance levels in female patients with ADHD (p=0.39), while the difference in the average control and case group was decreased.

Keywords: attention deficit hyperactivity disorder, interleukin 13, insulin resistance, high intensity by intervals training

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1043 Serum Interlukin-8 and Immunomodulation in Beta Thalassemia Patients

Authors: Shahira El Shafie, Hanaa Eldash, Engy Ghabbour, Mohamed Eid

Abstract:

Several immunologic defects can be found in patients with beta-thalassemia, among which the impairment of neutrophil phagocytic function is of utmost importance. Attention has been directed to the role of proinflammatory cytokines in neutrophil chemotaxis and phagocytosis. Interleukin-8 (IL-8) is an important chemotactic and activation peptide for neutrophils; changes in IL-8 level and potential correlation with neutrophil function can be relevant to immunomodulation pathophysiology in beta-thalassemia patients. This case-control study aimed to evaluate IL-8 level and to assess granulocyte recruitment, as markers of immunomodulation, in poly-transfused thalassemia patients attending Fayoum University Hospitals. The study was conducted on 50 patients with ß thalassemia and 32 age-matched controls. 21/50 patients were transfused more than ten times, and 29/50 were transfused in a lower frequency. Patients and controls were subjected to thorough history taking and clinical examination, measurement of IL-8 level using human IL-8 ELISA kit, and Rebuck skin window technique (RSWT) to assess granulocyte recruitment. Our data showed statistically significant higher levels of IL-8 in ß thalassemia patients compared to control with a much higher difference in patients transfused more than ten times. Neutrophil recruitment was significantly lower in ß thalassemia patients compared to control at 4 hours and 24 hours test time. Although IL-8, the main chemotactic pro-inflammatory cytokine showed a higher level in thalassemia patients, neutrophils recruitment was significantly lower, especially in those receiving more than ten transfusion times. Our findings suggest a possible role of other neutrophil chemotactic factors, defective neutrophil response, or increased IL-8 as compensation of abnormal function. We recommend the use of IL-8 and Rebuck skin window technique as useful markers of immunomodulation in thalassemia and further study for these biomarkers to assess their clinical implications and impact on the management of thalassemia patients.

Keywords: beta-thalassemia, Interleukin-8, Rebuck skin window technique, immunomodulation

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1042 Regression of Fibrosis by Apigenin in Thioacetamide-Induced Liver Fibrosis Rat Model through Suppression of HIF-1/FAK Pathway

Authors: Hany M. Fayed, Rehab F. Abdel-Rahman, Alyaa F. Hessin, Hanan A. Ogaly, Gihan F. Asaad, Abeer A. A. Salama, Sahar Abdelrahman, Mahmoud S. Arbid, Marwan Abd Elbaset Mohamed

Abstract:

Liver fibrosis is a serious global health problem that occurs as a result of a variety of chronic liver disorders. Apigenin, a flavonoid found in many plants, has several pharmacological properties. The aim of this study was to evaluate the antifibrotic efficacy of apigenin (APG) against experimentally induced hepatic fibrosis in rats via using thioacetamide (TAA) and to explore the possible underlying mechanisms. TAA (100 mg/kg, i.p.) was given three times each week for two weeks to induce liver fibrosis. After TAA injections, APG was given orally (5 and 10 mg/kg) daily for two weeks. Biochemical, molecular, histological and immunohistochemical analyses were performed on blood and liver tissue samples. The functioning of the liver, oxidative stress, inflammation, and liver fibrosis indicators were all evaluated. The findings showed that TAA markedly increased the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as the levels of malondialdehyde (MDA), focal adhesion kinase (FAK), hypoxia-inducible factor-1 (HIF-1), nuclear factor-κB (NF-κB), transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) with a reduction in albumin, total protein, A/G ratio, GSH content and interleukin-10 (IL-10). Moreover, TAA elevated the content of collagen I, α -smooth muscle actin (α-SMA), and hydroxyproline in the liver. The treatment with APG in a dose-dependent manner has obviously prevented these alterations and amended the harmful effects induced by TAA. The histopathological and immunohistochemical observations supported this biochemical evidence. The higher dose of APG produced the most significant antifibrotic effect. As a result of these data, APG appears to be a promising antifibrotic drug and could be used as a new herbal medication or dietary supplement in the future for the treatment of liver fibrosis. This effect might be related to the inhibition of the HIF-1/FAK signaling pathway.

Keywords: apigenin, FAK, HIF-1, liver fibrosis, rat, thioacetamide

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1041 Associations of Gene Polymorphism of IL-17 a (C737T) with Its Level in Patients with Erysipelas Kazakh Population

Authors: Nazira B. Bekenova, Lydia A. Mukovozova, Andrej M. Grjibovski, Alma Z. Tokayeva, Yerbol M. Smail, Nurlan E. Aukenov

Abstract:

Erysipelas is an infectious disease with socio-economic significance and prone to prolonged recurrent course (30%). Contribution of genetic factors, in particular the gene polymorphism of cytokines, can be essential in disease etiology and pathogenesis. Interleukin – 17 A are produced by T helpers of 17 type and plays a key role in development of local inflammation process. Local inflammatory process is a dominant in the clinic of erysipelas. Established that the skin and mucosas are primary areas of migration (homing) Th17-cell and their cytokines are stimulate the barrier function of the epithelium. We studied associations between gene polymorphism of IL-17A (C737T) rs 8193036 and IL-17A level in patients with erysipelas Kazakh population. Altogether, 90 cases with erysipelas and 90 healthy controls from an ethnic Kazakh population comprised the sample. Cases were identified at Clinical Infectious Diseases Hospital of Semey (Kazakhstan). The IL-17A (rs8193036) polymorphism was analyzed by a real time polymerase chain reaction. Plasma levels of IL-17 A were assessed by immuneenzyme analysis method using ‘Vector-Best’ test-system (Russia). Differences in levels of IL-17 A between CC, TT, CT groups were studied using Kruskal — Wallis test. Pairwise comparisons were performed using Mann-Whitney tests with Bonferroni correction (New significance level was set to 0.025). We found, that in patients with erysipelas with CC genotype the level of IL-17 A was higher (p= 0, 010) compared to the carriers of CT genotype. When compared the level of IL – 17 A between the patients with TT genotype and patients with CC genotype, also between the patients with CT genotype and patients with TT genotype statistically significant differences are not revealed (p = 0.374 and p = 0.043, respectively). Comparisons of IL-17 A plasma levels between the CC and CT genotypes, between the CC and TT genotypes, and between the TT and CT in healthy patients did not reveal significant differences (p = 0, 291). Therefore, we are determined the associations of gene polymorphism of IL-17 A (C737T) with its level in patients erysipelas carriers CC genotype.

Keywords: erysipelas, interleukin – 17 A, Kazakh, polymorphism

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1040 Trends of Cutaneous Melanoma in New Zealand: 2010 to 2020

Authors: Jack S. Pullman, Daniel Wen, Avinash Sharma, Bert Van Der Werf, Richard Martin

Abstract:

Background: New Zealand (NZ) melanoma incidence rates are amongst the highest in the world. Previous studies investigating the incidence of melanoma in NZ were performed for the periods 1995 – 1999 and 2000 – 2004 and suggested increasing melanoma incidence rates. Aim: The aim of the study is to provide an up-to-date review of trends in cutaneous melanoma in NZ from the New Zealand Cancer Registry (NZCR) 2010 – 2020. Methods: De-identified data were obtained from the NZCR, and relevant demographic and histopathologic information was extracted. Statistical analyses were conducted to calculate age-standardized incidence rates for invasive melanoma (IM) and melanoma in situ (MIS). Secondary results included Breslow thickness and melanoma subtype analysis. Results: There was a decline in the IM age-standardized incidence rate from 30.4 to 23.9 per 100,000 person-years between 2010 to 2020, alongside an increase in MIS incidence rate from 37.1 to 50.3 per 100,000 person-years. Men had a statistically significant higher IM incidence rate (p <0.001) and Breslow thickness (p <0.001) compared with women. Increased age was associated with a higher incidence of IM, presentation with melanoma of greater Breslow thickness and more advanced T stage. Conclusion: The incidence of IM in NZ has decreased in the last decade and was associated with an increase in MIS incidence over the same period. This can be explained due to earlier detection, dermoscopy, the maturity of prevention campaigns and/or a change in skin protection behavior.

Keywords: melanoma, incidence, epidemiology, New Zealand

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1039 Differences in Cognitive Functioning over the Course of Chemotherapy in Patients Suffering from Multiple Myeloma and the Possibility to Predict Their Cognitive State on the Basis of Biological Factors

Authors: Magdalena Bury-Kaminska, Aneta Szudy-Szczyrek, Aleksandra Nowaczynska, Olga Jankowska-Lecka, Marek Hus, Klaudia Kot

Abstract:

Introduction: The aim of the research was to determine the changes in cognitive functioning in patients with plasma cell myeloma by comparing patients’ state before the treatment and during chemotherapy as well as to determine the biological factors that can be used to predict patients’ cognitive state. Methods: The patients underwent the research procedure twice: before chemotherapy and after 4-6 treatment cycles. A psychological test and measurement of the following biological variables were carried out: TNF-α (tumor necrosis factor), IL-6 (interleukin 6), IL-10 (interleukin 10), BDNF (brain-derived neurotrophic factor). The following research methods were implemented: the Montreal Cognitive Assessment (MoCA), Battery of Tests for Assessing Cognitive Functions PU1, experimental and clinical trials based on the Choynowski’s Memory Scale, Stroop Color-Word Interference Test (SCWT), depression measurement questionnaire. Results: The analysis of the research showed better cognitive functions of patients during chemotherapy in comparison to the phase before it. Moreover, neurotrophin BDNF allows to predict the level of selected cognitive functions (semantic fluency and execution control) already at the diagnosis stage. After 4-6 cycles, it is also possible to draw conclusions concerning the extent of working memory based on the level of BDNF. Cytokine TNF-α allows us to predict the level of letter fluency during anti-cancer treatment. Conclusions: It is possible to presume that BDNF has a protective influence on patients’ cognitive functions and working memory and that cytokine TNF-α co-occurs with a diminished execution control and better material grouping in terms of phonological fluency. Acknowledgment: This work was funded by the National Science Center in Poland [grant no. 2017/27/N/HS6/02057.

Keywords: chemobrain, cognitive impairment, non−central nervous system cancers, hematologic diseases

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1038 Pioglitazone Ameliorates Methotrexate-Induced Renal Endothelial Dysfunction via Amending Detrimental Changes in Antioxidant Profile, Systemic Cytokines and Apoptotic Factors

Authors: Sahar M. El-Gowilly, Mai M. Helmy, Hanan M. El-Gowelli

Abstract:

Methotrexate (MTX) is widely used in treatment of cancers and autoimmune diseases. However, nephrotoxicity is one of the most important side effects of MTX. The peroxisome proliferator-activated receptor gamma agonist, pioglitazone (PIO), is known to exert anti-inflammatory and reno-protective effects in various kidney injuries. The purpose of this study was to investigate the potential involvement of endothelial damage in MTX-induced renal injury and to elaborate the possible protective effect of PIO against MTX-induced nephropathy. Compared with saline-treated rats, treatment with MTX (7 mg/kg for 3 day) caused significant elevations in serum levels of urea and creatinine, increased renal nitrate/nitrite level and impaired renovascular responsiveness of isolated perfused kidney to endothelium-dependent vasodilations induced by acetylcholine (0.01-2.43 nmol) and isoprenaline (1µmol). These effects were abolished by concurrent treatment with PIO (2.5 mg/kg, for 5 days starting two days before MTX). Alternatively, MTX treatment did not affect endothelium-independent renovascular relaxation induced by sodium nitroprusside (1-30 μmole). The possibility that alterations in renal antioxidants, circulating cytokine and apoptotic factor (Fas) levels contributed to MTX-PIO interaction was assessed. PIO treatment abrogated renal oxidative stress (decreased reduced glutathione and catalase activity and increased malondialdehyde), elevated serum cytokine (interleukin-6, interleukin-10, tumor necrosis factor-alpha and transforming growth factor-beta1) and Fas induced by MTX. Histologically, MTX caused defused tubular cells swelling and vacuolization associated with endothelial damage in renal arterioles. These effects disappeared upon co-treated with PIO. Collectively, PIO abolished MTX-induced endothelium dysfunction and nephrotoxicity via ameliorating oxidative stress and rectifying cytokines and Fas abnormalities caused by MTX.

Keywords: methotrexate, pioglitazone, endothelium, kidney

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1037 Pioglitazone Ameliorates Methotrexate-Induced Renal Endothelial Dysfunction via Amending Detrimental Changes in Antioxidant Profile, Systemic Cytokines and Fas Production

Authors: Sahar M. El-Gowilly, Mai M. Helmy, Hanan M. El-Gowelli

Abstract:

Methotrexate (MTX) is widely used in treatment of cancers and autoimmune diseases. However, nephrotoxicity is one of its most important side effects. The peroxisome proliferator-activated receptor gamma agonist, pioglitazone, is known to exert antiinflammatory and reno-protective effects in various kidney injuries. The purpose of this study was to investigate the potential involvement of endothelial damage in MTX-induced renal injury and to elaborate the possible protective effect of pioglitazone against MTX-induced endothelial impairment. Compared with saline-treated rats, treatment with MTX (7 mg/kg for 3 day) caused significant elevations in serum levels of urea and creatinine, increased renal nitrate/nitrite level and impaired renovascular responsiveness of isolated perfused kidney to endothelium-dependent vasodilations induced by acetylcholine (0.01-2.43 nmol) and isoprenaline (1µmol). These effects were abolished by concurrent treatment with pioglitazone (2.5 mg/kg, for 5 days starting two days before MTX). Alternatively, MTX treatment did not affect endothelium-independent renovascular relaxation induced by sodium nitroprusside (0.001-10 μmole). The possibility that alterations in renal antioxidants, circulating cytokine and apoptotic factor (Fas) levels contributed to MTX-pioglitazone interaction was assessed. Pioglitazone treatment abrogated renal oxidative stress (decreased reduced glutathione and catalase activity and increased malondialdehyde), elevated serum cytokine (interleukin-6, interleukin-10, tumor necrosis factor-alpha and transforming growth factor-beta1) and Fas induced by MTX. Histologically, MTX caused defused tubular cells swelling and vacuolization associated with endothelial damage in renal arterioles. These effects disappeared upon co-treated with pioglitazone. Collectively, pioglitazone abolished MTX-induced endothelium dysfunction and nephrotoxicity via ameliorating oxidative stress and rectifying cytokines and Fas abnormalities caused by MTX.

Keywords: methotrexate, pioglitazone, endothelium, kidney

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