Search results for: complement receptor 1

Authors: Vladimir Ryabov, Mikhail Baryshevs, Mikhail Voskresenskey, Boris Popov

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The human prostate gland (PG) samples were obtained from patients who had undergone radical prostatectomy for prostate cancer (PC) and used to extract total RNA and prepare the prostate stromal cell cultures (PSCC) and patients-derived organoids (PDO). Growth of the cell cultures was accessed under microscopic evaluation in transmitted light and the marker expression by reverse polymerase chain reaction (RT-PCR), immunofluorescence, and immunoblotting. Some PCR products from prostate tissue, PSCC, and PDO were cloned and sequenced. We found that the cells of early and late passages of PSCC and corresponding PDO expressed luminal (androgen receptor, AR; cytokeratin 18, CK18) and basal (CK5, p63) epithelial markers, the production of which decreased or disappeared in late PSCC and PDO. The PSCC and PDO of early passages from cancer tissue additionally produced cancer markers AMACR, TMPRSS2-ERG, and Ezh2. The expression of TMPRSS2-ERG fusion transcripts was verified by cloning and sequencing the PCR products. The results obtained suggest that early passages of PSCC might be used as a pre-clinical model for the evaluation of early markers of prostate cancer.

Keywords: localized prostate cancer, prostate epithelial markers, prostate cancer markers, AMACR, TMPRSS2-ERG, prostate stromal cell cultures, PDO

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Authors: Emeka Thaddues Njoku

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Since 2009, the Nigerian Government has established diverse counter-terrorism legislations and practices in response terrorism in North Eastern part of the country. However, these measures have hampered not only the ability of civil society organizations to sustain the autonomous spaces that define/locate them at the intersection between the state and public but also the balance between freedom and security. Hence, this study examines the various elements associated with the interface between the counter terrorism security framework of the government and the capacity of civil society organizations to carry out their mandates in Nigeria. In order to achieve this, the survey research of the ex-post facto type will be adopted using the multi-stage sampling technique. A total of two hundred (200) copies of questionnaire will be administered to members of the civil society organizations and 24 In-Depth Interviews (IDI) will be conducted for officials of security agencies, Ministry of Defence and operators of civil society organizations. Fifty respondents will be drawn from each civil society organisations in the areas of humanitarian assistance, human rights Advocacy, development-oriented, peace-building. Moreover, 24 interviewees drawn from the key members of the security agencies (6), Ministry of Defence (6) and 12 operators of civil society organizations-three respondents each will represent the four civil society organizations mentioned above. Also, secondary data will be used to complement In-depth Interview (IDI) sessions. All collected data will be coded and analysed using descriptive statistics of frequency counts and simple percentage in the Statistical Package for Social Science (SPSS). Content analysis will be used for the In-depth interview and secondary data.

Keywords: counter-terrorism, civil society organizations, freedom, terrorism

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Authors: Ya L. V., Benjamin Ong Wei Lin, Wanli Niu, Benjamin Seah Chin Tat

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This article introduces a methodology that improves reliability and cyclability of 2nd-life Li-ion battery system repurposed as an energy storage system (ESS). Most of the 2nd-life retired battery systems in the market have module/pack-level state-of-health (SOH) indicator, which is utilized for guiding appropriate depth-of-discharge (DOD) in the application of ESS. Due to the lack of cell-level SOH indication, the different degrading behaviors among various cells cannot be identified upon reaching retired status; in the end, considering end-of-life (EOL) loss and pack-level DOD, the repurposed ESS has to be oversized by > 1.5 times to complement the application requirement of reliability and cyclability. This proposed battery grading algorithm, using non-invasive methodology, is able to detect outlier cells based on historical voltage data and calculate cell-level historical maximum temperature data using semi-analytic methodology. In this way, the individual battery cell in the 2nd-life battery system can be graded in terms of SOH on basis of the historical voltage fluctuation and estimated historical maximum temperature variation. These grades will have corresponding DOD grades in the application of the repurposed ESS to enhance system reliability and cyclability. In all, this introduced battery grading algorithm is non-invasive, compatible with all kinds of retired Li-ion battery systems which lack of cell-level SOH indication, as well as potentially being embedded into battery management software for preventive maintenance and real-time cyclability optimization.

Keywords: battery grading algorithm, 2nd-life repurposing battery system, semi-analytic methodology, reliability and cyclability

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Authors: Hyun-Jong Choi, Minjun Kwak, Doo-Won Seo, Sang-Kuk Woo, Sun-Dong Kim

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Solid Oxide Cell(SOC) systems can contribute to the transition to the hydrogen society by utilized as a power and hydrogen generator by the electrochemical reaction with high efficiency at high operation temperature (>750 ℃). La1-xSrxCo1-yFeyO3, which is an air electrode, is occurred stability degradations due to reaction and delamination with yittria stabilized zirconia(YSZ) electrolyte in a water electrolysis mode. To complement this phenomenon SOCs need gadolinium doped ceria(GDC) buffer layer between electrolyte and air electrode. However, GDC buffer layer requires a high sintering temperature and it causes a reaction with YSZ electrolyte. This study carried out low temperature sintering of GDC layer by applying Cu-oxide as a sintering aid. The effect of a copper additive as a sintering aid to lower the sintering temperature for the construction of solid oxide fuel cells (SOFCs) was investigated. GDC buffer layer with 0.25-10 mol% CuO sintering aid was prepared by reacting GDC power and copper nitrate solution followed by heating at 600 ℃. The sintering of CuO-added GDC powder was optimized by investigating linear shrinkage, microstructure, grain size, ionic conductivity, and activation energy of CuO-GDC electrolytes at temperatures ranging from 1100 to 1400 ℃. The sintering temperature of the CuO-GDC electrolyte decreases from 1400 ℃ to 1100 ℃ by adding the CuO sintering aid. The ionic conductivity of the CuO-GDC electrolyte shows a maximum value at 0.5 mol% of CuO. However, the addition of CuO has no significant effects on the activation energy of GDC electrolyte. GDC-LSCF layers were co-sintering at 1050 and 1100 ℃ and button cell tests were carried out at 750 ℃.

Keywords: Co-Sintering, GDC-LSCF, Sintering Aid, solid Oxide Cells

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Authors: A. M. Iordache, S. M. Iordache, V. Barna, M. Elisa, I. C. Vasiliu, C. R. Stefan, I. Chilibon, I. Stamatin, S. Caramizoiu, C. E. A. Grigorescu

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The general objective of the presentation is the development of an e-tongue like sensor based on modified screen printed electrode (SPE) structures with a receptor part made of porphyrins/metalloporphyrins chemically bound to graphene (the sensitive assembly) to act as antennas and “capture” the histamine molecules. Using a single, ultra-sensitive electrochemical sensor, we measured the concentration of histamine, a compound which is strongly connected to the level of freshness in foods (the caution level of histamine is 50 ppm, whereas the maximum accepted levels range from 200 ppm to 500 ppm). Our approach for the chemical immobilization of the porphyrins onto the surface of the graphenes was via substitution reaction: a solution of graphene in SOCl2 was heated to 800C for 6 hours. Upon cooling, the metallo-porphyrins were added and ultrasonicated for 4 hours. The solution was then allowed to cool to room temperature and then centrifuged in order to separate the deposit. The sensitive assembly was drop casted onto the carbon SPE and cyclic voltammetry was performed in the presence of histamine. The reaction is quasi-reversible and the sensor showed an oxidation potential for histamine at 600 mV. The results indicate a linear dependence of concentration of histamine as function of intensity. The results are reproducible; however the chemical stability of the sensitive assembly is low.

Keywords: histamine, cyclic voltammetry, metallo-porphyrin, food freshness

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Authors: Hanna Poikonen, Petri Toiviainen, Mari Tervaniemi

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Event-related potentials (ERPs) evoked by simple tones in the brain have been extensively studied. However, in reality the music surrounding us is spectrally and temporally complex and dynamic. Thus, the research using natural sounds is crucial in understanding the operation of the brain in its natural environment. Music is an excellent example of natural stimulation, which, in various forms, has always been an essential part of different cultures. In addition to sensory responses, music elicits vast cognitive and emotional processes in the brain. When compared to laymen, professional musicians have stronger ERP responses in processing individual musical features in simple tone sequences, such as changes in pitch, timbre and harmony. Here we show that the ERP responses evoked by rapid changes in individual musical features are more intense in musicians than in laymen, also while listening to long excerpts of the composition Carmen. Interestingly, for professional dancers, the amplitudes of the cognitive P300 response are weaker than for musicians but still stronger than for laymen. Also, the cognitive P300 latencies of musicians are significantly shorter whereas the latencies of laymen are significantly longer. In contrast, sensory N100 do not differ in amplitude or latency between musicians and laymen. These results, acquired from a novel ERP methodology for natural music, suggest that we can take the leap of studying the brain with long pieces of natural music also with the ERP method of electroencephalography (EEG), as has already been made with functional magnetic resonance (fMRI), as these two brain imaging devices complement each other.

Keywords: electroencephalography, expertise, musical features, real-life music

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Authors: P. Siriarchawatana, K. Leungchavaphongse, N. Covavisaruch, K. Rojananuangnit, P. Boondaeng, N. Panyayingyong

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Glaucoma is a disease that causes visual loss in adults. Glaucoma causes damage to the optic nerve and its overall pathophysiology is still not fully understood. Vasculopathy may be one of the possible causes of nerve damage. Photographic imaging of retinal vessels by fundus camera during eye examination may complement clinical management. This paper presents an innovation for measuring central light reflex width-to-retinal vessel diameter ratio (CRR) from digital retinal photographs. Using our edge detection technique, CRRs from glaucoma and normal eyes were compared to examine differences and associations. CRRs were evaluated on fundus photographs of participants from Mettapracharak (Wat Raikhing) Hospital in Nakhon Pathom, Thailand. Fifty-five photographs from normal eyes and twenty-one photographs from glaucoma eyes were included. Participants with hypertension were excluded. In each photograph, CRRs from four retinal vessels, including arteries and veins in the inferotemporal and superotemporal regions, were quantified using edge detection technique. From our finding, mean CRRs of all four retinal arteries and veins were significantly higher in persons with glaucoma than in those without glaucoma (0.34 vs. 0.32, p < 0.05 for inferotemporal vein, 0.33 vs. 0.30, p < 0.01 for inferotemporal artery, 0.34 vs. 0.31, p < 0.01 for superotemporal vein, and 0.33 vs. 0.30, p < 0.05 for superotemporal artery). From these results, an increase in CRRs of retinal vessels, as quantitatively measured from fundus photographs, could be associated with glaucoma.

Keywords: glaucoma, retinal vessel, central light reflex, image processing, fundus photograph, edge detection

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Authors: Ghazi Chabchoub, Mouna Feki, Mohamed Abid, Hammadi Ayadi

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Autoimmune thyroid diseases (AITDs), including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are inherited as complex traits. Genetic factors associated with AITDs have been tentatively identified by candidate gene and genome scanning approaches. We analysed three intragenic microsatellite markers in the thyroid hormone receptor associated protein 2 gene (THRAP2), mapped near D12S79 marker, which have a potential role in immune function and inflammation [THRAP2-1(TG)n, THRAP2-2 (AC)n and THRAP2-3 (AC)n]. Our study population concerned 12 patients affected with AITDs belonging to a multiplex Tunisian family with high prevalence of AITDs. Fluorescent genotyping was carried out on ABI 3100 sequencers (Applied Biosystems USA) with the use of GENESCAN for semi-automated fragment sizing and GENOTYPER peak-calling software. Statistical analysis was performed using the non parametric Lod score (NPL) by Merlin software. Merlin outputs non-parametric NPLall (Z) and LOD scores and their corresponding asymptotic P values. The analysis for three intragenic markers in the THRAP2 gene revealed strong evidence for linkage (NPL=3.68, P=0.00012). Our results suggested the possible role of THRAP2 gene in AITDs susceptibility in this family.

Keywords: autoimmunity, autoimmune disease, genetic, linkage analysis

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Authors: Nir Wittenberg, Moshe Farhi

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This mixed-methods study examines the integration of artificial intelligence (AI) tools in a first-year social work course to assess their potential for enhancing professional knowledge and skills. The incorporation of digital technologies, such as AI, in social work interventions, training, and research has increased, with the expectation that AI will become as commonplace as email and mobile phones. However, policies and ethical guidelines regarding AI, as well as empirical evaluations of its usefulness, are lacking. As AI is gradually being adopted in the field, it is prudent to explore AI thoughtfully in alignment with pedagogical goals. The outcomes assessed include professional identity, course satisfaction, and motivation. AI offers unique reflective learning opportunities through personalized simulations, feedback, and queries to complement face-to-face lessons. For instance, AI simulations provide low-risk practices for situations such as client interactions, enabling students to build skills with less stress. However, it is essential to recognize that AI alone cannot ensure real-world competence or cultural sensitivity. Outcomes related to student learning, experience, and perceptions will help to elucidate the best practices for AI integration, guiding faculty, and advancing pedagogical innovation. This strategic integration of selected AI technologies is expected to diversify course methodology, improve learning outcomes, and generate new evidence on AI’s educational utility. The findings will inform faculty seeking to thoughtfully incorporate AI into teaching and learning.

Keywords: artificial intelligence (AI), social work education, students, developing a professional identity, ethical considerations

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Authors: Fabiola Trejo Perez, Rolando Diaz Loving

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Sexual pleasure consists of the positively valued feelings induced by sexual stimuli, but it is also weighed down by pop-psychological baggage, and subjected to cross-cultural and cross-historical variation. Social and individual interpretations of what can or can’t be considered as pleasurable are intertwined with culture’s predominant values, norms and beliefs. For each culture, sexual norms work as a guide to be followed in order to model socially accepted behaviors. Therefore, cultural messages regarding sexuality are usually directed to restrict men and women from enjoyment, sexual satisfaction and specifically orgasm. Given that sexual pleasure hasn’t been recognized as an accepted topic of open discussion, particularly for women, people have to eventually complement their knowledge using their own experience filling in the blanks from what little has been said. Thus, this research aims to identify which are the particular social messages associated with the easing or inhibition of sexual pleasure. Three hundred Mexican men and women ages 25 to 35 years old answered a self-report survey composed by the Inventory of facilitators and inhibitors of sexual pleasure and the Sexual premises questionnaire via pencil-paper and online. Results show a high endorsement to double standard messages associated with higher levels of sexual pleasure inhibitors like feeling pressured to have sexual activity, guilt and inability to reach orgasm, in contrast with people who endorse more permissive norms and beliefs, feeling connected to their sexual partners and confident with themselves. These results illustrate that the shaping of sexuality, from experience to society, is comprised of an important relationship between culture and sexual pleasure.

Keywords: culture, sexual double standard, sexual norms and beliefs, sexual pleasure

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Authors: Leila Anoosheh

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Aim: The aim of this study was to assess The effects of aerobic training on microRNA let-7a expression and levels of tumor tissue IL-6 in mice with breast cancer. Method: Twenty BALB/c c mice (4-5 weeks,17 gr mass) were cancerous by injection of estrogen-dependent receptor breast cancer cells MC4-L2 and divided into two groups: tumor-training(TT) and tumor-control(TC) group. Then TT group completed aerobic training for 6 weeks, 5 days per week (14-18 m/min). After tumor emersion, tumor width and length were measured by digital caliper every week. 48 hours after the last exercise subjects were killed. Tissue sampling were collected and stored in -70ᵒ. Tumor tissue was homogenized and let-7a expression and IL-6 levels were accounted with Real time-PCR and ELISA Kit respectively. Statistical analysis of let-7a was conducted by the REST software. Repeated measures and independent tests were used to assess tumor size and IL-6, respectively. Results: Tumor size and IL-6 levels were significantly decreased in TT group compare with TC group (p<0.05). microRNA let-7a was increased significantly in TT against control group respectively (p=0/000). Conclusion: Reduction in tumor size, followed by aerobic exercise can be attributed to the loss of inflammatory factors such as IL-6; It seems that regarding to up regulation effects of aerobic exercise training on let-7a and down regulation effects of that on IL-6 in mice with breast cancer, This type of training can be used as adjuvant therapy in conjunction with other therapies for breast cancer.

Keywords: breast cancer, aerobic training, microRNA let-7a, IL-6

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Authors: Roudabeh Vakil Monfared, Farhad Mashayekhi

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Breast cancer is the most common malignancy type among women with about 1 million new cases each year. The immune system plays an important role in the breast cancer development. OX40L (also known as TNFSF4), a membrane protein, which is a member of the tumor necrosis factor super family binds to its receptor OX40 and this co-stimulation has a crucial role in T-cell proliferation, survival and cytokine release. Due to the importance of the T-cells in anti-tumor activities of OX40L we studied the association of rs3850641 (T→C) polymorphism of OX40L gene with breast cancer. The study included 123 women with breast cancer and 126 healthy volunteers with no signs of cancer. Genomic DNA was extracted from blood leucocytes. Genotype and allele frequencies were determined in patients and control cases with the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the analysis was performed by Med Calc. The prevalence of genotype frequencies of TT, CT and CC were 60.9%, 30.08% and 8.9 % in patients with breast cancer and 74.6 %, 18.25 % and 7.14 % in healthy volunteers while the T and C allelic frequency was 76.01% and 23.98 % in patients and 83.73% and 16.26% in healthy controls. Respectively Statistical analysis has shown no significant difference from the comparison of either genotype (P=0.06). According to these results, the rs3850641 SNP has no association with the susceptibility of breast cancer in a population in northern Iran. However, further studies in larger populations including other genetic and environmental factors are required to achieve conclusion.

Keywords: OX40L, gene, polymorphism, breast cancer

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Authors: Debasish Pradhan, Shaktiprasad Pradhan, Rakesh Kumar Pradhan, Gitanjali Tripathy

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Suppressors of cytokine signalling (SOCS1), a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signalling pathway. The current study has uncovered that SOCS1 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS1 on MDR, we analyzed the expression of P-gp and SOCS1 by immunohistochemistry and found there was a positive correlation between them. At that point, we effectively interfered with RNA translation by the contamination of siRNA of SOCS1 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi, the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise, the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flow cytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS1 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: breast cancer, multidrug resistance, SOCS1 gene, MDR1 gene, RNA interference

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Authors: Samkeliso S. Ndzimandze, Welldone Moyo, Oranso T. Mahlangu, Adolph A. Muleja, Alex T. Kuvarega, Thabo T. I. Nkambule

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The high cost of precursor materials has hindered the commercialization of ceramic membrane technology in water treatment. In this work, a ceramic membrane disc (approximately 50 mm in diameter and 4 mm thick) was prepared from low-cost starting materials, kaolin, and fly ash by pressing at 200 bar and calcining at 900 °C. The fabricated membrane was characterized for various physicochemical properties, natural organic matter (NOM) removal as well as fouling propensity using several techniques. Further, the ceramic membrane was tested on samples collected from four drinking water treatment plants in KwaZulu-Natal, South Africa (named plants 1-4). The membrane achieved 48.6%, 54.6%, 57.4%, and 76.4% bulk UV254 reduction for raw water at plants 1, 2, 3, and 4, respectively. These removal rates were comparable to UV254 reduction achieved by coagulation/flocculation steps at the respective plants. Further, the membrane outperformed sand filtration steps in plants 1-4 in removing disinfection by-product precursors (8%-32%) through size exclusion. Fluorescence excitation-emission matrices (FEEM) studies showed the removal of fluorescent NOM fractions present in the water samples by the membrane. The membrane was fabricated using an up-scalable facile method, and it has the potential for application as a polishing step to complement conventional processes in water treatment for drinking purposes.

Keywords: crossflow filtration, drinking water treatment plants, fluorescence excitation-emission matrices, ultraviolet 254 (UV₂₅₄)

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Authors: Sdiqeh Jalali, M. R. Khazdair

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Liver X receptors (LXR) have an essential role in the regulation of cholesterol metabolism, and their activation increase ABCG5 and ABCG8 genes expression for the improvement of cholesterol excretion from the body during reverse cholesterol transport (RCT). The aim of this study was to investigate the effects of high-intensity interval (HIT) and low intensity continuous (LIT) trainings on gene expression of these substances after a high-fat diet in Wistar rats. Materials and Methods: Fifteen male Wistar rats were divided into 3 groups: control group (n = 5), HIT exercise group (n = 5) and LIT exercise group (n = 5). All groups used a high-fat diet for 13 weeks, and the HIT and LIT groups performed the specific training program. The expression of LXRβ, ABCG5, and ABCG8 genes was measured after the training period. Findings: Data analysis showed significantly higher levels of LXRβ, ABCG5, and ABCG8 gene expression in HIT and LIT groups compared to the control group (P ≤ 0.05). Conclusion: HIT and LIT trainings after a high-fat diet have beneficial effects on RCT that prevent heart attack. Also, HIT training may have a greater effect on cholesterol excretion during the reverse cholesterol transport mechanism than LIT.

Keywords: liver X receptor, atherosclerosis, interval training, endurance training

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Authors: Naif Al-Jomah, Falah H Al-Mohanna, Abdelilah Aboussekhra

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Active breast cancer-associated fibroblasts (CAFs), the most influential cells in breast tumor microenvironment, express/secrete high levels of the proinvasive/metastatic interleukin-6 (IL-6). Therefore, we have tested here the effect of the IL-6 receptor (IL-6R) inhibitor tocilizumab (TCZ; Actemra) on different active breast CAFs. We have shown that TCZ potently and persistently suppresses the expression of various CAF biomarkers, namely α-SMA, SDF-1 as well as the STAT3 pathway and its downstream target AUF1. TCZ also inhibited the proliferation, migration and invasion abilities of active breast CAF cells. Additionally, TCZ repressed the ability of CAF cells in promoting epithelial-to-mesenchymal transition, and enhancing the migratory/invasive and proliferative capacities of breast cancer cells in vitro. Importantly, these findings were confirmed in orthotopic humanized breast tumors in mice. Furthermore, TCZ suppressed the expression of the pro-angiogenic factor VEGF-A and its transactivator HIF-1α in CAF cells, and consequently inhibited the angiogenic-promoting effect of active CAFs both in vitro and in orthotopic tumor xenografts. These results indicate that inhibition of the IL-6/STAT3/AUF1 pathway by TCZ can normalize active breast CAFs and suppress their paracrine pro-carcinogenic effects, which paves the way toward development of specific CAF-targeting therapy, badly needed for more efficient breast cancer treatments.

Keywords: angiogenesis, interleukin-6, paracrine, cancer-associated fibroblasts

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Authors: Uzma Saqib, Mirza S. Baig

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Myeloid differentiation primary response protein 88 (MYD88) has long been considered a central player in the inflammatory pathway. Recent studies clearly suggest that it is an important therapeutic target in inflammation. On the other hand, a recent study on the interaction between the orphan nuclear receptor (Nur77) and p38α, leading to increased lipopolysaccharide-induced hyperinflammatory response, suggests this binary complex as a therapeutic target. In this study, we have designed inhibitors that can inhibit both MYD88 and Nur77 at the same time. Since both MYD88 and Nur77 are an integral part of the pathways involving lipopolysaccharide-induced activation of NF-κB-mediated inflammation, we tried to target both proteins with the same library in order to retrieve compounds having dual inhibitory properties. To perform this, we developed a homodimeric model of MYD88 and, along with the crystal structure of Nur77, screened a virtual library of compounds from the traditional Chinese medicine database containing ~61,000 compounds. We analyzed the resulting hits for their efficacy for dual binding and probed them for developing a common pharmacophore model that could be used as a prototype to screen compound libraries as well as to guide combinatorial library design to search for ideal dual-target inhibitors. Thus, our study explores the identification of novel leads having dual inhibiting effects due to binding to both MYD88 and Nur77 targets.

Keywords: drug design, Nur77, MYD88, inflammation

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Authors: Barbora Chmelova, Radek Sachl

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Gangliosides are amphipathic membrane lipids. Due to the composition of bulky oligosaccharide chains containing one or more sialic acids linked to the hydrophobic ceramide base, gangliosides are classified among glycosphingolipids. This unique structure induces a high self-aggregating tendency of gangliosides and, therefore, the formation of nanoscopic clusters called nanodomains. Gangliosides are preferentially present in an extracellular membrane leaflet of all human tissues and thus have an impact on a huge number of biological processes, such as intercellular communication, cell signalling, membrane trafficking, and regulation of receptor activity. Defects in their metabolism, impairment of proper ganglioside function, or changes in their organization lead to serious health conditions such as Alzheimer´s and Parkinson´s diseases, autoimmune diseases, tumour growth, etc. This work mainly focuses on ganglioside organization into nanodomains and their dynamics within the plasma membrane. Current research investigates static ganglioside nanodomains characterization; nevertheless, the information about their diffusion is missing. In our study, fluorescence correlation spectroscopy is implemented together with stimulated emission depletion (STED-FCS), which combines the diffraction-unlimited spatial resolution with high temporal resolution. By comparison of the experiments performed on model vesicles containing 4 % of either GM1, GM2, or GM3 and Monte Carlo simulations of diffusion on the plasma membrane, the description of ganglioside clustering, diffusion of nanodomains, and even diffusion of ganglioside molecules inside investigated nanodomains are described.

Keywords: gangliosides, nanodomains, STED-FCS, flourescence microscopy, membrane diffusion

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Authors: Sony Baral, Harald Vacik

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This study analyzes the sustainability of community forest management in two community forests in Terai and Hills of Nepal, representing four forest types: 1) Shorearobusta, 2) Terai hardwood, 3) Schima-Castanopsis, and 4) other Hills. The sustainability goals for this region include maintaining and enhancing the forest stocks. Considering this, we analysed changes in species composition, stand density, growing stock volume, and growth-to-removal ratio at 3-5 year intervals from 2005-2016 within 109 permanent forest plots (57 in the Terai and 52 in the Hills). To complement inventory data, forest users, forest committee members, and forest officials were consulted. The results indicate that the relative representation of economically valuable tree species has increased. Based on trends in stand density, both forests are being sustainably managed. Pole-sized trees dominated the diameter distribution, however, with a limited number of mature trees and declined regeneration. The forests were over-harvested until 2013 but under-harvested in the recent period in the Hills. In contrast, both forest types were under-harvested throughout the inventory period in the Terai. We found that the ecological dimension of sustainable forest management is strongly achieved while the economic dimension is lacking behind the current potential. Thus, we conclude that maintaining a large number of trees in the forest does not necessarily ensure both ecological and economical sustainability. Instead, priority should be given on a rational estimation of the annual harvest rates to enhance forest resource conditions together with regular benefits to the local communities.

Keywords: community forests, diversity, growing stock, forest management, sustainability, nepal

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Authors: Arūnas Gudinavičius, Andrius Šuminas

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The analysis of scholarly journals formats is fragmented and needs to be studied from a point of view of scientific communication. While PDF is to the author’s best knowledge probably the most popular digital format of XXI century, but there are more formats available: HTML, EPUB, etc. Our aim is to analyze how these formats important to the readers and what is their contribution to scientific communication. We want to investigate how printed journals are still popular between scholars and does different formats are preferred between fields of science . In most cases, publishing of scientific journals are examined from a narrow perspective of a particular university science affair administrators or research funding institution. We believe that more data o n formats used in scholarly periodicals currently published in Lithuania as well as in Eastern Europe are needed. Science communication is often analyzed as a directed chain of information in the author-publisher-reader cycle. The paper is focusing on the publishing part of this chain. A distinction is made between formal and informal forms of scientific communication, which is relevant in today's context, when both forms of communication intertwine and complement each other. In our research, we will analyze formal documentary (formats of publication of scientific articles) communication - scientific information recorded in a certain medium and formatted in certain format (printed, PDF, HTML, EPUB, etc.). In our research, we will analyze the stage of publication of research results in scientific journals and their dissemination through specific publication formats. The paper is to systematize and analyze the various types of formats of scientific journal published in XXI century in Lithuania (small publishing market). The research analyses the case of small European country and presents publishing formats characteristics of the publication of scientific periodicals.

Keywords: scientific communication, scientific journals, publishing formats, reading

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Authors: Bello Gonzalez, Setten Van M., Brouwer M.

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The chicken small intestine represents a dynamic and complex organ in which the enzymatic digestion and absorption of nutrients take place. The development of an in vitro fermentation chicken small intestinal model could be used as an alternative to explore the interaction between the microbiota and nutrient metabolism and to enhance the efficacy of targeting interventions to improve animal health. In the present study we have developed an in vitro fermentation chicken ileum microbiota model for unrevealing the complex interaction of ileum microbial community under physiological conditions. A two-vessel continuous fermentation process simulating in real-time the physiological conditions of the ileum content (pH, temperature, microaerophilic/anoxic conditions, and peristaltic movements) has been standardized as a proof of concept. As inoculum, we use a pool of ileum microbial community obtained from chicken broilers at the age of day 14. The development and validation of the model provide insight into the initial characterization of the ileum microbial community and its dynamics over time-related to nutrient assimilation and fermentation. Samples can be collected at different time points and can be used to determine the microbial compositional structure, dynamics, and diversity over time. The results of studies using this in vitro model will serve as the foundation for the development of a whole small intestine in vitro fermentation chicken gastrointestinal model to complement our already established in vitro fermentation chicken caeca model. The insight gained from this model could provide us with some information about the nutritional strategies to restore and maintain chicken gut homeostasis. Moreover, the in vitro fermentation model will also allow us to study relationships between gut microbiota composition and its dynamics over time associated with nutrients, antimicrobial compounds, and disease modelling.

Keywords: broilers, in vitro model, ileum microbiota, fermentation

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Authors: E. M. Vieira, C. S. Vieira, L. P. Bonifácio, L. M. de Oliveira Ciabati, A. C. A. Franzon, F. S. Zaratini, J. A. C. Sanchez, M. S. Andrade, J. P. Dias de Souza

Abstract:

The quality of prenatal care is key to reduce maternal morbidity and mortality. Communication between the health service and users can stimulate prevention and care. M-health has been an important and low cost strategy to health education. The PRENACEL programme (prenatal in the cell phone) was developed. It consists of a programme of information via SMS from the 20^th week of pregnancy up to 12^th week after delivery. Messages were about prenatal care, birth, contraception and breastfeeding. Communication of the pregnant woman asking questions about their health was possible. The objective of this study was to evaluate the implementation of PRENACEL as a useful complement to the standard prenatal care. Twenty health clinics were selected and randomized by cluster, 10 as the intervention group and 10 as the control group. In the intervention group, women and their partner were invited to participate. The control group received the standard prenatal care. All women were interviewed in the immediate post-partum and in the 12^th and 24^th week post-partum. Most women were married, had more than 8 years of schooling and visit the clinic more than 6 times during prenatal care. The intervention group presented lowest percentage of higher economic participants (5.6%), less single mothers and no drug user. It also presented more prenatal care visits than the control group and it was less likely to present Severe Acute Maternal Mortality when compared to control group as well as higher percentage of partners (75.4%) was present at the birth compared to control group. Although the study is still being carried out, preliminary data are showing positive results of the compliance of women to prenatal care.

Keywords: cellphone, health technology, prenatal care, prevention

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Authors: So Youn Park, Yi Sle Lee, Ki Whan Hong, Chi Dae Kim

Abstract:

The role of metabolism in the pathogenesis of osteoarthritis is an emerging field. Metabolic alterations may be a role in osteoarthritis (OA) pathogenesis, and these changes influence joint destruction via several cytokine. Especially, in OA patients, levels of IL-1β are elevated in the synovial fluid, synovial membrane, subchondral bone, and cartilage. The IL-1β is activated by NLRP3 inflammasomes, and NLRP3 inflammasomes are cytosolic complexes that drive the production of other inflammatory cytokines, including IL-1β. In this study, we examined that SIRT1 suppresses IL-1β through inhibiting NLRP3 inflammasomes and SIRT1 ameliorates osteoarthritis. OA fibroblasts were isolated from synovium of OA patients. IL-1β and NLRP3 were detected in synovium of OA patients by immunohistochemistry. Lipopolysaccharides (LPS) stimulated the expression of active IL-1β mRNA in OA fibroblasts and combination of LPS, and adenosine triphosphate increased more the expression of active IL-1β in OA fibroblasts. The level of IL-1β was measured by western blot and ELISA assay. NLRP3 inflammasomes complex were measured by western blot. SIRT1 did not inhibit expression of NLRP3 inflammasome. So caspase-1, apoptotic speck-like protein containing a caspase recruitment domain (ASC) and NLRP3 protein were expressed in OA fibroblasts. But SIRT1 suppressed activation of IL-1β by inhibiting activity of caspase-1 via NLRP3 inflammasome in OA fibroblasts under LPS plus ATP stimulation. These results suggest that SIRT1 is a modulator of NLRP3 inflammasomes in OA fibroblasts and ameliorate IL-1β, so expression of SIRT1 in OA fibroblast may be a potential strategy for OA inflammation treatment.

Keywords: osteoarthritis, inflammasome, SIRT1, IL-1beta

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Authors: Preet Singh, Kavitha Kongara, Dave Harding, Neil Ward, Paul Chambers

Abstract:

The objective of this study was to compare the analgesic efficacy of opiorphin and its analogue with a mu-receptor agonist; morphine. Opiorphins (Gln-Arg-Phe-Ser-Arg) belong to the family of endogenous enkephalinase inhibitors, found in saliva of humans. They are inhibitors of two Zinc metal ectopeptidases (Neutral endopeptidase NEP, and amino-peptidase APN) which are responsible for the inactivation of the endogenous opioids; endorphins and enkephalins. Morphine and butorphanol exerts their analgesic effects by mimicking the actions of endorphins and enkephalins. The opiorphin analogue was synthesized based on the structure activity relationship of the amino acid sequence of opiorphin. The pharmacological profile of the analogue was tested by replacing Serine at position 4 with Proline. The hot plate and tail flick test were used to demonstrate the analgesic efficacy. There was a significant increase in the time for the tail flick response after an injection of opiorphin, which was similar to the morphine effect. There was no increase in time in the hot plate test after an injection of opiorphin. The results suggest that opiorphin works at spinal level only rather than both spinal and supraspinal. Further work is required to confirm our results. We did not find analgesic activity of the opiorphin analogue. Thus, Serine at position 4 is also important for its pharmacological action. Further work is required to illustrate the role of serine at position 4 in opiorphin.

Keywords: analgesic peptides, endogenous opioids, morphine, opiorphin

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Authors: Syed M. Shahid, Rozeena Shaikh, Syeda N. Nawab, Abid Azhar

Abstract:

Diabetes mellitus (DM) is a prevalent non-communicable disease worldwide. DM may lead to many vascular complications like hypertension, nephropathy, retinopathy, neuropathy and foot infections. Pathogenesis of diabetic nephropathy (DN) is implicated by the polymorphisms in genes encoding the specific components of renin angiotensin aldosterone system (RAAS) which include angiotensinogen (AGT), angiotensin-II receptor and angiotensin converting enzyme (ACE) genes. This study was designed to explore the possible association of AG (M268T) polymorphism in the patients of diabetes and nephropathy in Pakistan. Study subjects included 100 controls, 260 diabetic patients without renal insufficiency and 190 diabetic nephropathy patients with persistent albuminuria. Fasting blood samples were collected from all the subjects after getting institutional ethical approval and informed consent. The biochemical estimations, PCR amplification and direct sequencing for the specific region of AGT gene was carried out. A significantly high frequency of TT genotype and T allele of AGT (M268T) was observed in the patients of diabetes with nephropathy as compared to controls and diabetic patients without any known renal impairment. The TT genotype and T allele of AGT (M268T) polymorphism may be considered as a genetic risk factor for the development and progression of nephropathy in diabetes. Further cross sectional population studies would be of help to establish and confirm the observed possible association of AGT gene variations with development of nephropathy in diabetes.

Keywords: RAAS, AGT (M268T), diabetes, nephropathy

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Authors: Peter Jin

Abstract:

Ever since the recent resurgence of interest in political theorist Carl Schmitt’s work, much of the current analysis on Schmitt has fo-cused on evaluating Schmitt’s legacy by exposing contradictions in his rationale. Rather than condemn such contradictions, this paper instead seeks to analyze these contradictions in an effort to better understand the radical shift in Schmitt’s intellectual trajectory from an astute critic of liberal democracy to a fascist apologist towards the end of the Weimar period. An essential part of this change is his interest in what Schmitt called ‘the emergence of aesthetics.’ Schmitt diagnosed the underlying issue with the aesthetic in the political sphere to be its irrationalism, indifference, and indeci-siveness. For Schmitt, the latter two of these were especially prob-lematic for two of his key concepts: the ‘political’ and ‘the shared historical reality.’ Schmitt’s radical depiction of ‘the political’ as an existential opposition of allegiances that necessitated a state of emergency and a decisionist sovereign political struggle required an equally radical justification, or Schmitt’s call for ‘a shared his-torical reality’ not based in historical fact yet able to mobilize the masses. In this way, Schmitt clearly condemns the indifferent, indecisive aesthetic that runs against his decisionist, action-oriented political theory. Yet despite his firm stance against aestheticism, Schmitt himself used the evocative and irrational power of aesthet-icism as a tool to present his own ‘political myth’ that compelled believers to join in decisive unity against a common enemy. In short, Schmitt’s contradictions on aestheticism and his creation of a ‘political myth’ suggest that Schmitt’s underlying conflict with aestheticism was not as much of an issue of irrationality as it was a chronic preoccupation with coercing concrete action at the expense of rational deliberation.

Keywords: aesthetics of the political, Carl Schmitt, political myth, Weimar democracy

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Authors: Harish Rajak, Swati Singh

Abstract:

A series of novel pyrimidine based semicarbazone were designed and synthesized on the basis of semicarbazone based pharmacophoric model to satisfy the structural prerequisite crucial for antiepileptic activity. The semicarbazones based pharmacophoric model consists of following four essential binding sites: (i) An aryl hydrophobic binding site with halo substituent; (ii) A hydrogen bonding domain; (iii) An electron donor group and (iv) Another hydrophobic-hydrophilic site controlling the pharmacokinetic features of the anticonvulsant. The aryl semicarbazones has been recognized as a structurally novel class of compounds with remarkable anticonvulsant activity. In the present study, all the test semicarbazones were subjected to molecular docking using Glide v5.8. Some of the compounds were found to interact with ARG192, GLU270 and THR353 residues of 1OHV protein, present in GABA-AT receptor. The chemical structures of the synthesized molecules were characterized by elemental and spectral (IR, 1H NMR, 13C NMR and MS) analysis. The anticonvulsant activities of the compounds were investigated using maximal electroshock seizure (MES) and subcutaneous pentylenetrtrazole (scPTZ) models. The neurotoxicity was evaluated in mice by the rotorod test. The attempts were also made to establish structure-activity relationships among synthesized compounds. The results of the present study confirmed that the pharmacophore model with four binding sites is essential for antiepileptic activity.

Keywords: pyrimidine, semicarbazones, anticonvulsant activity, neurotoxicity

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Authors: S. Roy, R. Rekha, K. Sriram, G. Subhadra, R. Johana

Abstract:

Cardiovascular disease remains a leading cause of death in most industrialized countries. Many chemical drugs are available in the market which targets different receptor proteins related to cardiovascular diseases. Of late the traditional herbal drugs are safer when compared to chemical drugs because of its side effects. However, many herbal remedies used in treating cardiovascular diseases have not undergone scientific assessment to prove its pharmacological activities. There are many natural compounds, nature derived and Natural product mimic compounds are available which are in the market as approved drug. In the most of the cases drug activity at the molecular level are not known. Here we have categorized those compounds with our experimental compounds in different classes based on the structural similarity and physicochemical properties, using a tool, Chemmine and has attempted to understand the mechanism of the action of a experimental compound, which are clustered with Simvastatin, Lovastatin, Mevastatin and Pravastatin. Target protein molecule for Simvastatin, Lovastatin, Mevastatin and Pravastatin is HMG-CoA reductase, so we concluded that the experimental compound may be able to bind to the same target. Molecular docking and atomic interaction studies with simvastatin and our experimental compound were compared. A pharmacophore modeling was done based on the experimental compound and HMG-CoA reductase inhibitor.

Keywords: molecular docking, physicochemical properties, pharmacophore modeling structural similarity, pravastatin

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Authors: Huafeng Wei

Abstract:

Dementia in Alzheimer’s Disease (AD) is the number one cause of dementia internationally, without effective treatments. Increasing evidence suggest that disruption of intracellular calcium homeostasis, primarily pathological elevation of cytosol and mitochondria but reduction of endoplasmic reticulum (ER) calcium concentrations, play critical upstream roles on multiple pathologies and associated neurodegeneration, impaired neurogenesis, synapse, and cognitive dysfunction in various AD preclinical studies. The last federal drug agency (FDA) approved drug for AD dementia treatment, memantine, exert its therapeutic effects by ameliorating N-methyl-D-aspartate (NMDA) glutamate receptor overactivation and subsequent calcium dysregulation. More research works are needed to develop other drugs targeting calcium dysregulation at multiple pharmacological acting sites for future effective AD dementia treatment. Particularly, calcium channel blockers for the treatment of hypertension and dantrolene for the treatment of muscle spasm and malignant hyperthermia can be repurposed for this purpose. In our own research work, intranasal administration of dantrolene significantly increased its brain concentrations and durations, rendering it a more effective therapeutic drug with less side effects for chronic AD dementia treatment. This review summarizesthe progress of various studies repurposing drugs targeting calcium dysregulation for future effective AD dementia treatment as potentially disease-modifying drugs.

Keywords: alzheimer, calcium, cognitive dysfunction, dementia, neurodegeneration, neurogenesis

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Authors: Huafeng Wei

Abstract:

Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

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