Search results for: complement receptor 1

Authors: Changde Zhang, Qiang Zhang, Shilong Zheng, Jiawang Liu, Shanchun Guo, Qiu Zhong, Guangdi Wang

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Fulvestrant was approved by FDA to treat breast cancer as a selective estrogen receptor downregulator (SERD) with intramuscular injection administration. ZB716, a fulvestarnt-3 boronic acid, is an SERD with comparable anticancer effect to fulvestrant, but could produce good pharmacokinetic properties under oral administration with mice or rat models. To understand why ZB716 produced much better oral bioavailability, it was proposed that the boronic acid blocked the phase II direct biotransformation with the hydroxyl group on the 3 position of the aromatic ring on fulvestrant. In this study, ZB716 or fulvestrant was incubated with human liver microsome and oxidation cofactor NADPH in vitro. Their metabolites after oxidation were profiled with the Q-Exactive, a high-resolution mass spectrometer. The result showed that ZB716 blocked the forming of hydroxyl groups on its benzene ring except for the oxidation of C-B bond forming fulvestrant in its metabolites, and the concentration of fulvestrant with one more hydroxyl group found in the metabolites from incubation with fulvestrant was about 34 fold high as that formed from incubation with ZB716. Compared to fulvestrant, ZB716 is expected to be much difficult to be further bio-transformed into more hydrophilic compounds, to be difficult excreted out of blood system, and to have longer residence time in blood, which can lead to higher oral bioavailability. This study provided evidence to explain the high bioavailability of ZB716 after oral administration from the perspective of its difficulty of oxidation, a phase I biotransformation, on positions on its aromatic ring.

Keywords: biotransformation, fulvestrant, metabolite profiling, ZB716

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Authors: Charles Iledun Oyewole

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The daunting challenge that the ‘man with the hoe’ is going to face in the coming decades will be complex and interwoven. With global population already above 7 billion people, it has been estimated that food (crop) production must more than double by 2050 to meet up with the world’s food requirements. Nigeria population is also expected to reach over 240 million people by 2050, at the current annual population growth of 2.61 per cent. The country’s farming population is estimated at over 65 per cent, but the country still depends on food importation to complement production. The small scale farmer, who depends on simple hand tools: hoes and cutlasses, remains the centre of agricultural production, accounting for 90 per cent of the total agricultural output and 80 per cent of the market flow. While the hoe may have been a tool for sustainable development at a time in human history, this role has been smothered by population growth, which has brought too many mouths to be fed (over 170 million), as well as many industries to fuel with raw materials. It may then be argued that the hoe is unfortunately not a tool for the coming challenges and that agricultural mechanization should be the focus. However, agriculture as an enterprise is a ‘complete wheel’ which does not work when broken, particularly, in respect to mechanization. Generally, mechanization will prompt increase production, where land is readily available; increase production, will require post-harvest handling mechanisms, crop processing and subsequent storage. An important aspect of this is readily available and favourable markets for such produce; fuel by good agricultural policies. A break in this wheel will lead to the process of mechanization crashing back to subsistence production, and probably reversal to the hoe. The focus of any agricultural policy should be to chart a course for sustainable mechanization that is environmentally friendly, that may ameliorate Nigeria’s food and raw material gaps. This is the focal point of this article.

Keywords: Crop production, Farmer, Hoes, Mechanization, Policy framework, Population, Growth, Rural areas

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Authors: Youjeong Hwang

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Purpose: Insulin-like growth factor-I (IGF-I) promotes B-cell development, immunoglobulin formation, and interleukin-6 (IL-6) production, then regulate the immune response and inflammation. As IGF-I and their receptor also exist in the periodontal tissue, they may affect the immune response caused by periodontal pathogens in aggressive periodontitis (AgP) patients. The function of IGF is regulated by IGF binding proteins (IGFBPs), and IGFBP-3 is known to most abundant in plasma. The aim of the present study was to assess the concentration of IGF-I and IGFBP-3 in plasma and gingival crevicular fluid (GCF) in AgP patients and to find out their association. Methods: Nine patients with AgP (test group) and nine healthy subjects (control group) were included in this study. None of the subjects had a history of systemic disease, smoking or steroids medication. GCF samples were collected by microcapillary pipettes and plasma samples were obtained by venipuncture. Probing pocket depth (PD), clinical attachment level (CAL) and bleeding on probing (BOP) were recorded. Samples were assayed for IGF-I and IGFBP-3 levels using ELISA. Results: Mean IGF-I level in GCF was higher in the test group than control. Mean IGF-I level in plasma and IGFBP-3 level in GCF and plasma in control group were higher than that of the test group. However, there was no statistical significance (p > 0.05). The mean level of IGF-I and IGFBP-3 in GCF was lower than those in plasma. Mean IGF-I level in plasma showed a negative correlation with PD and CAL (p < 0.05) in both groups. The levels of IGF-I and IGFBP-3 in GCF seemed to be negatively correlated with BOP in the test group (p < 0.05). Conclusions: The difference in the level of IGF-I and IGFBP-3 between AgP and healthy subjects was not significant. Further studies that explain the mechanism of the protective role of IGF-I with more samples are needed.

Keywords: aggressive periodontitis, pathogenesis, insulin-like growth factor, insulin-like growth factor binding protein

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Authors: Yasser A. Ahmed, Juleen M Dickson, Evan S. Krystofiak, Julie A. Oliver

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Cancer cells urgently need folate to support their rapid division. Folate receptors (FR) are over-expressed on a wide range of tumor cells, including breast cancer cells. FR are distributed over the entire surface of cancer cells, but are polarized to the apical surface of normal cells. Targeting of cancer cells using specific surface molecules such as folate receptors may be one of the strategies used to kill cancer cells without hurting the neighing normal cells. The aim of the current study was to try a method of SEM detecting FR in a murine breast cancer cell model (4T1 cells) using secondary antibody conjugated to gold or gold-coated magnetite nanoparticles. 4T1 cells were suspended in RPMI medium witth FR antibody and incubated with secondary antibody for fluorescence microscopy. The cells were cultured on 30mm Thermanox coverslips for 18 hours, labeled with FR antibody then incubated with secondary antibody conjugated to gold or gold-coated magnetite nanoparticles and processed to scanning electron microscopy (SEM) analysis. The fluorescence microscopy study showed strong punctate FR expression on 4T1 cell membrane. With SEM, the labeling with gold or gold-coated magnetite conjugates showed a similar pattern. Specific labeling occurred in nanoparticle clusters, which are clearly visualized in backscattered electron images. The 4T1 tumor cell model may be useful for the development of FR-targeted tumor therapy using gold-coated magnetite nano-particles.

Keywords: cancer cell, nanoparticles, cell culture, SEM

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Authors: Wajid Rehman, Sirajul Haq, Bakhtiar Muhammad, Syed Fahad Hassan, Amin Badshah, Muhammad Waseem, Fazal Rahim, Obaid-Ur-Rahman Abid, Farzana Latif Ansari, Umer Rashid

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Five novel triorganotin (IV) compounds have been synthesized and characterized. The tin atom is penta-coordinated to assume trigonal-bipyramidal geometry. Using in silico derived parameters; the objective of our study is to design and synthesize promiscuous antibacterials potent enough to combat resistance. Among various synthesized organotin (IV) complexes, compound 5 was found as potent antibacterial agent against various bacterial strains. Further lead optimization of drug-like properties was evaluated through in silico predictions. Data mining and computational analysis were utilized to derive compound promiscuity phenomenon to avoid drug attrition rate in designing antibacterials. Xanthine oxidase and human glucose- 6-phosphatase were found as only true positive off-target hits by ChEMBL database and others utilizing similarity ensemble approach. Propensity towards a-3 receptor, human macrophage migration factor and thiazolidinedione were found as false positive off targets with E-value 1/4> 10^-4 for compound 1, 3, and 4. Further, displaying positive drug-drug interaction of compound 1 as uricosuric was validated by all databases and docked protein targets with sequence similarity and compositional matrix alignment via BLAST software. Promiscuity of the compound 5 was further confirmed by in silico binding to different antibacterial targets.

Keywords: antibacterial activity, drug promiscuity, ADMET prediction, metallo-pharmaceutical, antimicrobial resistance

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Authors: Azza H. El-Medany, Hanan H. Hagar, Jamila H. El-Medany

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Ulcerative colitis (UC) is one of chronic inflammatory diseases primarily affecting colon with unknown etiology. Some researches papers mentioned the possibility of the use of drugs that affect the angiotensin II in reducing the complication of ulcerative colitis. The aim of the present study is to evaluate the potential protective and therapeutic effects of captopril and valsartan on ulcerative colitis induced experimentally in rats using acetic acid. The results were assessed by histological assessment of colonic tissues and measurement of malondialdehyde (MDA), tumor necrosis factor (TNF-α), transforming growth factor (TGF-1B), angiotensin converting enzyme (ACE), reduced glutathione (GSH) and platelet activating factor (PAF) levels in colonic tissues. Oral pre-treatment with captopril or valsartan in a dose of 30 mgkg-1 body weight for 2 weeks before induction of colitis (prophylactic groups) and continuously for 2 weeks after induction (therapeutic groups) significantly reduce MDA, TNF-α, PAF, TGF-1B and ACE levels in colonic tissues as compared to acetic acid control group. Also, a significant increase in GSH level was observed in colonic tissues. Captopril and valsartan attenuated the macroscopic and microscopic colonic damage induced by acetic acid. These results suggest that either captopril or valsartan may be effective as prophylactic or treatment of UC through inhibition of ACE and scavenging effect on oxygen-derived free radicals.

Keywords: captopril, valsartan, angiotensin converting enzyme, reduced glutathione, tumor necrosis factor

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Authors: R. Pravin Kumar, L. Roopa

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Enzymes are molecular machines used in various industries such as pharmaceuticals, cosmetics, food and animal feed, paper and leather processing, biofuel, and etc. Nevertheless, this has been possible only by the breath-taking efforts of the chemists and biologists to evolve/engineer these mysterious biomolecules to work the needful. Main agenda of this enzyme engineering project is to derive screening and selection tools to obtain focused libraries of enzyme variants with desired qualities. The methodologies for this research include the well-established directed evolution, rational redesign and relatively less established yet much faster and accurate insilico methods. This concept was initiated as a Receptor Rependent-4Dimensional Quantitative Structure Activity Relationship (RD-4D-QSAR) to predict kinetic properties of enzymes and extended here to study transaminase by a 7D QSAR approach. Induced-fit scenarios were explored using Quantum Mechanics/Molecular Mechanics (QM/MM) simulations which were then placed in a grid that stores interactions energies derived from QM parameters (QMgrid). In this study, the mutated enzymes were immersed completely inside the QMgrid and this was combined with solvation models to predict descriptors. After statistical screening of descriptors, QSAR models showed > 90% specificity and > 85% sensitivity towards the experimental activity. Mapping descriptors on the enzyme structure revealed hotspots important to enhance the enantioselectivity of the enzyme.

Keywords: QMgrid, QM/MM simulations, RD-4D-QSAR, transaminase

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Authors: Joseph A. Bentil, Anders Thygesen, Lene Langea, Moses Mensah, Anne Meyer

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The study investigated the saccharification potential of in-house enzymes produced from a white-rot basidiomycete strain, Polyporus ciliatus CBS 366.74. The in-house enzymes were produced by growing the fungus on mono and composite substrates of cocoa pod husk (CPH) and green seaweed (GS) (Ulva lactuca sp.) with and without the addition of 25mM ammonium nitrate at 4%w/v substrate concentration in submerged condition for 144 hours. The crude enzyme extracts preparations (CEE 1-5 and CEE 1-5+AN) obtained from the fungal cultivation process were sterile-filtered and used as enzyme sources for enzymatic hydrolysis of hydrothermally pretreated corn stover using a commercial cocktail enzyme, Cellic Ctec3, as benchmark. The hydrolysis was conducted at 50ᵒC with 50mM sodium acetate buffer, pH 5 based on enzyme dosages of 5 and 10 CMCase Units/g biomass at 1%w/v dry weight substrate concentration at time points of 6, 24, and 72 hours. The enzyme activity profile of the in-house enzymes varied among the growth substrates with the composite substrates (50-75% GS and AN inclusion), yielding better enzyme activities, especially endoglucanases (0.4-0.5U/mL), β-glucosidases (0.1-0.2 U/mL), and xylanases (3-10 U/mL). However, nitrogen supplementation had no significant effect on enzyme activities of crude extracts from 100% GS substituted substrates. From the enzymatic hydrolysis, it was observed that the in-house enzymes were capable of hydrolysing the pretreated corn stover at varying degrees; however, the saccharification yield was less than 10%. Consequently, theoretical glucose yield was ten times lower than Cellic Ctec3 at both dosage levels. There was no linear correlation between glucose yield and enzyme dosage for the in-house enzymes, unlike the benchmark enzyme. It is therefore recommended that the in-house enzymes are used to complement the dosage of commercial enzymes to reduce the cost of biomass saccharification.

Keywords: enzyme production, hydrolysis yield, feedstock, enzyme blend, Polyporus ciliatus

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Authors: L. C. Ansanelli, P. Alfredini

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The article presents the evaluation of the effectiveness of two groins located at Gonzaguinha and Milionários Beaches, situated on the southeast coast of Brazil. The effectiveness of these coastal defense structures is evaluated in terms of sedimentary dynamics, which is one of the most important environmental processes to be assessed in coastal engineering studies. The applied method is based on the implementation of the Delft3D numerical model system tools. Delft3D-WAVE module was used for waves modelling, Delft3D-FLOW for hydrodynamic modelling and Delft3D-SED for sediment transport modelling. The calibration of the models was carried out in a way that the simulations adequately represent the region studied, evaluating improvements in the model elements with the use of statistical comparisons of similarity between the results and waves, currents and tides data recorded in the study area. Analysis of the maximum wave heights was carried to select the months with higher accumulated energy to implement these conditions in the engineering scenarios. The engineering studies were performed for two scenarios: 1) numerical simulation of the area considering only the two existing groins; 2) conception of breakwaters coupled at the ends of the existing groins, resulting in two “T” shaped structures. The sediment model showed that, for the simulated period, the area is affected by erosive processes and that the existing groins have little effectiveness in defending the coast in question. The implemented T structures showed some effectiveness in protecting the beaches against erosion and provided the recovery of the portion directly covered by it on the Milionários Beach. In order to complement this study, it is suggested the conception of further engineering scenarios that might recover other areas of the studied region.

Keywords: coastal engineering, coastal erosion, Sao Vicente bay, Delft3D, coastal engineering works

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Authors: Eric Fang, Robert Chen, Ghim Song Chia, Bien Soo Tan

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Objective and Rationale: Training of radiology residents hinges on practical, on-the-job training in all facets and modalities of diagnostic radiology. Although residency is structured to be comprehensive, clinical exposure depends on the case mix available locally and during the posting period. To supplement clinical training, there are several e-learning resources available to allow for greater exposure to radiological cases. The objective of this study was to survey residents and faculty on the usefulness of these e-learning resources. Methods: E-learning resources were shortlisted with input from radiology residents, Google search and online discussion groups, and screened by their purported focus. Twelve e-learning resources were found to meet the criteria. Both radiology residents and experienced radiology faculty were then surveyed electronically. The e-survey asked for ratings on breadth, depth, testing capability and user-friendliness for each resource, as well as for rankings for the top 3 resources. Statistical analysis was performed using SAS 9.4. Results: Seventeen residents and fifteen faculties completed an e-survey. Mean response rate was 54% ± 8% (Range: 14- 96%). Ratings and rankings were statistically identical between residents and faculty. On a 5-point rating scale, breadth was 3.68 ± 0.18, depth was 3.95 ± 0.14, testing capability was 2.64 ± 0.16 and user-friendliness was 3.39 ± 0.13. Top-ranked resources were STATdx (first), Radiopaedia (second) and Radiology Assistant (third). 9% of responders singled out R-ITI as potentially good but ‘prohibitively costly’. Statistically significant predictive factors for higher rankings are familiarity with the resource (p = 0.001) and user-friendliness (p = 0.006). Conclusion: A good e-learning system will complement on-the-job training with a broad case base, deep discussion and quality trainee evaluation. Based on our study on twelve e-learning resources, no single program fulfilled all requirements. The perception and use of radiology e-learning resources depended more on familiarity and user-friendliness than on content differences and testing capability.

Keywords: e-learning, medicine, radiology, survey

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Authors: Masocorro Gawned, Stephen Myers, Guat Siew Chew

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Nuclear Receptors (NR) are a super family of transcription factors that play a major role in lipid and glucose metabolism in skeletal muscle. Recently, pharmacological evidence supports the view that stimulation of nuclear receptors alleviates Type 2 Diabetes (T2D). The orphan nuclear receptors (ONR) are members of the nuclear receptor (NR) superfamily whose ligands and physiological functions remain unknown. To date, no systematic studies have been carried out to screen for ONRs expressed in insulin resistant (IR) skeletal muscle cells. Therefore, in this study, we have established a model for IR by treating C2C12 skeletal muscle cells with insulin (10nM) for 48 hours. Western Blot analysis of phosphorylated AKT confirmed IR. Real-time quantitative polymerase chain reaction (qPCR) results highlighted key ONRs including NUR77 (NR4A1), NURR1 (NR4A2) and NOR1 (NR4A3) which have been associated with fatty acid oxidation regulation and glucose homeostasis. Increased mRNA expression levels of estrogen-related receptors (ERRs), REV-ERBα, NUR77, NURR1, NOR1, in insulin resistant C2C12 skeletal muscle cells, indicated that these ONRs could potentially play a pivotal regulatory role of insulin secretion in lipid metabolism. Taken together, this study has successfully contributed to the complete analysis of ONR in IR, and has filled in an important void in the study and treatment of T2D.

Keywords: type 2 diabetes, orphan nuclear receptors, transcription receptors, quantitative mRNA expression

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Authors: Jou-An Chung

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The purpose of this study is to investigate the verb bias of the Mandarin verbs in children’s reading materials and provide the criteria for categorization. Verb bias varies cross-linguistically. As Mandarin and English are typological different, this study hopes to shed light on Mandarin verb bias with the use of corpus and provide thorough and detailed criteria for analysis. Moreover, this study focuses on children’s reading materials since it is a significant issue in understanding children’s sentence processing. Therefore, investigating verb bias of Mandarin verbs in children’s reading materials is also an important issue and can provide further insights into children’s sentence processing. The small corpus is built up for this study. The corpus consists of the collection of school textbooks and Mandarin Daily News for children. The files are then segmented and POS tagged by JiebaR (Chinese segmentation with R). For the ease of analysis, the one-word character verbs and intransitive verbs are excluded beforehand. The total of 20 high frequency verbs are hand-coded and are further categorized into one of the three types, namely DO type, SC type and other category. If the frequency of taking Other Type exceeds the threshold of 25%, the verb is excluded from the study. The results show that 10 verbs are direct object bias verbs, and six verbs are sentential complement bias verbs. The paired T-test was done to assure the statistical significance (p = 0.0001062 for DO bias verb, p=0.001149 for SC bias verb). The result has shown that in children’s reading materials, the DO biased verbs are used more than the SC bias verbs since the simplest structure of sentences is easier for children’s sentence comprehension or processing. In sum, this study not only discussed verb bias in child's reading materials but also provided basic coding criteria for verb bias analysis in Mandarin and underscored the role of context. Sentences are easier for children’s sentence comprehension or processing. In sum, this study not only discussed verb bias in child corpus, but also provided basic coding criteria for verb bias analysis in Mandarin and underscored the role of context.

Keywords: corpus linguistics, verb bias, child language, psycholinguistics

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Authors: Xiaoping Su, Gabriel G. Malouf

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Introduction: Breast cancer is a heterogeneous disease that can be classified in 4 subgroups using transcriptional profiling. The role of lncRNA expression in human breast cancer biology, prognosis, and molecular classification remains unknown. Methods and results: Using an integrative comprehensive analysis of lncRNA, mRNA and DNA methylation in 900 breast cancer patients from The Cancer Genome Atlas (TCGA) project, we unraveled the molecular portraits of 1,700 expressed lncRNA. Some of those lncRNAs (i.e, HOTAIR) are previously reported and others are novel (i.e, HOTAIRM1, MAPT-AS1). The lncRNA classification correlated well with the PAM50 classification for basal-like, Her-2 enriched and luminal B subgroups, in contrast to the luminal A subgroup which behaved differently. Importantly, estrogen receptor (ESR1) expression was associated with distinct lncRNA networks in lncRNA clusters III and IV. Gene set enrichment analysis for cis- and trans-acting lncRNA showed enrichment for breast cancer signatures driven by breast cancer master regulators. Almost two third of those lncRNA were marked by enhancer chromatin modifications (i.e., H3K27ac), suggesting that lncRNA expression may result in increased activity of neighboring genes. Differential analysis of gene expression profiling data showed that lncRNA HOTAIRM1 was significantly down-regulated in basal-like subtype, and DNA methylation profiling data showed that lncRNA HOTAIRM1 was highly methylated in basal-like subtype. Thus, our integrative analysis of gene expression and DNA methylation strongly suggested that lncRNA HOTAIRM1 should be a tumor suppressor in basal-like subtype. Conclusion and significance: Our study depicts the first lncRNA molecular portrait of breast cancer and shows that lncRNA HOTAIRM1 might be a novel tumor suppressor.

Keywords: lncRNA profiling, breast cancer, HOTAIRM1, tumor suppressor

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Authors: Iahtasham Khan, Vania Lucia De Assis Santana, Marcilia Maria Alves De Souza, Mabel Hanna Vance Harrop, Fernando Leandro Dos Santos, Cecília Maria Souza Leão E. Silva, Pedro Paulo Silveira, Marcelo Brasil, Marcus Vinícius, Hélio Cordeiro Manso Filho, Muhammad Younus, Aman Ullah Khan

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Glanders ranks high on clinical lists in some regions of Brazil as a cause of respiratory and lymphatic disease in equids. Glanders is caused by Burkolderia mallei (B. mallei) Gram-negative bacterium. B. mallei was first biological agent used in World War I in 20th century. The complement fixation test (CFT) is a serodiagnostic tool prescribed by the World Organization for Animal Health (OIE)for the diagnosis of glanders in the international trade of equids. The aim of the present study was to monitor the serological responses in equines naturally infected with B. mallei using the CFT. A total of 574 equids were tested with CFT, 30 days apart in a total of 12 samplings. One hundred thirty-four sera tested negative in all samplings; 192 sera tested positive in one sampling and 125 sera tested positive in two or more samplings. Remaining 123 samples showed uncertain results. Thus, CFT results can vary over a period of time. These variations could be the consequence of the effects of the natural immune response in each animal. The findings of the present study demonstrate difficulties regarding the simultaneous implementation of CFT and test and slaughter policies to eradicate glanders. Another constraint to control this disease is the presence of carrier/transitory CFT-negative animals, which are a potential source of disease in glanders-free areas. Serodiagnostic tests of higher sensitivity and specificity like immunobloat should be implemented to achieve success in the eradication of glanders.

Keywords: glanders, equids, horses, immunological, mules

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Authors: Benchouala Amira, Bojic Clement, Poupin Pascal, Cossu Leguille-carole

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The objective of this study is to evaluate in vitro the cytotoxic and androgenic potential of several antifungal molecules (amphotericin B, econazole, ketoconazole and miconazole) on MDA-Kb2 cell lines. This biological model is an effective tool for the detection of endocrine disruptors because it responds well to the main agonist of the androgen receptor (testosterone) and also to an antagonist: flutamide. The cytotoxicity of each chemical compound tested was measured using an MTT assay (tetrazolium salt, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) which measures the activity of the reductase function of mitochondrial succinate dehydrogenase enzymes of cultured cells. This complementary cytotoxicity test is essential to ensure that the effects of reduction in luminescence intensity observed during androgenic tests are only attributable to the anti-androgenic action of the compounds tested and not to their possible cytotoxic properties. Tests of the androgenic activity of antifungals show that these compounds do not have the capacity to induce transcription of the luciferase gene. These compounds do not exert an androgenic effect on MDA-Kb2 cells in culture for the environmental concentrations tested. The addition of flutamide for the same tested concentrations of antifungal molecules reduces the luminescence induced by amphotericin B, econazole and miconazole, which is explained by a strong interaction of these molecules with flutamide which may have a greater toxic effect than when tested alone. The cytotoxicity test shows that econazole and ketoconazole can cause cell death at certain concentrations tested. This cell mortality is perhaps induced by a direct or indirect action on deoxyribonucleic acid (DNA), ribonucleic acid (RNA) or proteins necessary for cell division.

Keywords: cytotoxicity, androgenic potential, antifungals, MDA-Kb2

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Authors: Okhee Woo

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Purpose: The aim of this study is to evaluate 2-year cumulative effective radiation dose and cumulative organ dose on regular follow-up computed tomography (CT) scans in patients with breast cancer and to establish personalized low-dose CT protocol. Methods and Materials: A retrospective study was performed on the patients with breast cancer who were diagnosed and managed consistently on the basis of routine breast cancer follow-up protocol between 2012-01 and 2016-06. Based on ICRP (International Commission on Radiological Protection) 103, the cumulative effective radiation doses of each patient for 2-year follow-up were analyzed using the commercial radiation management software (Radimetrics, Bayer healthcare). The personalized effective doses on each organ were analyzed in detail by the software-providing Monte Carlo simulation. Results: A total of 3822 CT scans on 490 patients was evaluated (age: 52.32±10.69). The mean scan number for each patient was 7.8±4.54. Each patient was exposed 95.54±63.24 mSv of radiation for 2 years. The cumulative CT radiation dose was significantly higher in patients with lymph node metastasis (p = 0.00). The HER-2 positive patients were more exposed to radiation compared to estrogen or progesterone receptor positive patient (p = 0.00). There was no difference in the cumulative effective radiation dose with different age groups. Conclusion: To acknowledge how much radiation exposed to a patient is a starting point of management of radiation exposure for patients with long-term CT follow-up. The precise and personalized protocol, as well as iterative reconstruction, may reduce hazard from unnecessary radiation exposure.

Keywords: computed tomography, breast cancer, effective radiation dose, cumulative organ dose

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Authors: Mukhtar Raban

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As part of Nelson Mandela University’s journey of repositioning its learning and teaching agenda, the university adopted and foregrounded a humanizing pedagogy-aligning with institutional goals of critically transforming the academic project. The university established the Humanizing Pedagogy Praxis and Research Niche (HPPRN) as a centralized hub for coordinating institutional work exploring and advancing humanizing pedagogies and tasked the unit with developing and enacting a model for humanizing pedagogy exploration. This investigation endeavored to report on the development and enactment of a model that sought to institutionalize a humanizing pedagogy at a South African university. Having followed a qualitative approach, the investigation presents the case study of Nelson Mandela University’s HPPRN and the model it subsequently established and enacted for the advancement towards a more common institutional understanding, interpretation and application of the humanizing pedagogy. The study adopted an interpretive lens for analysis, complementing the qualitative approach of the investigation. The primary challenge that confronted the HPPRN was the development of a ‘living model’ that had to complement existing institutional initiatives while accommodating a renewed spirit of critical reflection, innovation and research of continued and new humanizing pedagogical exploration and applications. The study found that the explicit consideration of tenets of humanizing and critical pedagogies in underpinning and framing the HPPRN Model contributed to the sense of ‘lived’ humanizing pedagogy experiences during enactment. The multi-leveled inclusion of critical reflection in the development and enactment stages was found to further the processes of praxis employed at the university, which is integral to the advancement of humanizing and critical pedagogies. The development and implementation of a model that seeks to institutionalize the humanizing pedagogy at a university rely not only on sound theoretical conceptualization but also on the ‘richness of becoming more human’ explicitly expressed and encountered in praxes and application.

Keywords: humanizing pedagogy, critical pedagogy, institutional implementation, praxis

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Authors: Milad Gholizadeh

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Asthma and chronic obstructive pulmonary disease (COPD) are very shared inflammatory diseases of the airlines. They togethercause airway tapering and are cumulative in occurrence throughout the world, imposing huge burdens on health care. It is currently recognized that some asthmatic inflammation is neutrophilic, controlled by the TH17 subset of helper T cells, and that some eosinophilic inflammation is controlled by type 2 innate lymphoid cells (ILC2 cells) temporary together with basophils. Patients who have plain asthma or are asthmatic patients who smoke with topographies of COPD-induced inflammation and might advantage from treatments targeting neutrophils, countingmacrolides, CXCR2 antagonists, phosphodiesterase 4 inhibitors, p38 mitogen-activating protein kinase inhibitors, and antibodies in contradiction of IL-1 and IL-17.Viral and bacterial infections, not only reason acute exacerbations of COPD, but also intensify and continue chronic inflammation in steady COPD through pathogen-associated molecular patterns. Present treatment plans are absorbed on titration of inhaled therapies such as long-acting bronchodilators, with cumulative interest in the usage of beleaguered biologic therapies meant at the underlying inflammatory devices. Educationssuggest that the mucosal IgA reply is abridged in COPD, and a lacking conveyance of IgA across the bronchial epithelium in COPD has been recognized, perhaps involving neutrophil proteinases, which may damage the Ig receptor mediating this transepithelialdirection-finding. Future instructions for investigation will emphasis elucidating the diverse inflammatory signatures foremost to asthma and chronic obstrucive, the development of reliable analytic standards and biomarkers of illness, and refining the clinical organization with an eye toward targeted therapies.

Keywords: imminology, asthma, COPD, CXCR2 antagonists

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Authors: Rozeena Shaikh, Syed M Shahid, Jamil Ahmad, Qaisar Mansoor, Muhammad Ismail, Abid Azhar

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Introduction: Diabetes mellitus (DM) is a prevalent non-communicable disease worldwide. In most high-income countries as well as middle-income and low- income countries. DM is among the top causes of deaths. DM may lead to many vascular complications like hypertension, nephropathy, retinopathy, neuropathy, and foot. Diabetic nephropathy (DN) characterized by persistent albuminuria is a leading cause of end stage renal failure (ESRF). Pathogenesis of diabetic nephropathy is implicated by the polymorphisms in genes encoding the components of reninangiotensin- aldosteron system (RAAS) which include angiotensinogen (AGT), angiotensin-II receptor and particularly angiotensin converting enzyme (ACE) gene. Method: Study subjects include 110 control, 110 patients with DM without hypertension, 110 patients with DM with hypertension and 110 patients with DN. Blood samples were collected for Biochemical analysis and PCR and sequencing for the specific region of both genes. Results: The frequency of DD genotype and D allele of ACE (I/D) was significantly (p<0.05) high in DM normotensive, DM hypertensive and DN patients when compared to control. The ACE G2350A genotypes and allele frequencies were significantly different (p<0.05) in DM hypertensive patients as compared to control and DN, while no difference was observed between DM normotensive and DN when compared to control. The genotypes and alleles of AGT (M268T) polymorphism were significantly different (p<0.05) in DM normotensive, DM hypertensive and DN when compared to control. Conclusion: The DD genotype and D allele of ACE (I/D), GG genotype and G allele of ACE (G2350A) and the TT genotype and T allele of AGT (M268T) polymorphism have shown a significant difference in genotype and allele frequencies between controls and patients.

Keywords: genetic variations, ACE, AGT, diabetes mellitus, diabetic nephropathy, Pakistan

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Authors: Amenador Kate Benedicta, Wang Zhiwei

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Since the later parts of the 20th century, the notion of equivalence continues to be a central and critical concept in the development of translation theory. After decades of arguments over word-for-word and free translations methods, scholars attempting to develop more systematic and efficient translation theories began to focus on fundamental translation concepts such as equivalence. Although the concept of equivalence has piqued the interest of many scholars, its definition, scope, and applicability have sparked contentious arguments within the discipline. As a result, several distinct theories and explanations on the concept of equivalence have been put forward over the last half-century. Thus, this study explores and discusses the evolution of the critical concept of equivalence in translation studies through a bibliometric method of investigation of manual and digital books and articles by analyzing different scholars' key contributions and limitations on equivalence from various theoretical perspectives. While analyzing them, emphasis is placed on the innovations that each theory has brought to the comprehension of equivalence. In order to achieve the aim of the study, the article began by discussing the contributions of linguistically motivated theories to the notion of equivalence in translation, followed by functionalist-oriented contributions, before moving on to more recent advancements in translation studies on the concept. Because equivalence is such a broad notion, it is impossible to discuss each researcher in depth. As a result, the most well-known names and their equivalent theories are compared and contrasted in this research. The study emphasizes the developmental progression in our comprehension of the equivalence concept and equivalent effect. It concluded that the various theoretical perspective's contributions to the notion of equivalence rather complement and make up for the limitations of each other. The study also highlighted how troublesome the equivalent concept might become in terms of identifying the nature of translation and how central and unavoidable the concept is in every translation action, despite its limitations. The significance of the study lies in its synthesis of the different contributions and limitations of the various theories offered by scholars on the notion of equivalence, lending literature to both student and scholars in the field, and providing insight on future theoretical development

Keywords: equivalence, functionalist translation theories, linguistic translation approaches, translation theories, Skopos

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Authors: Divya Vohora, Md. Jamir Anwar

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Antiepileptic drugs (AEDs)-induced adverse consequences on bone are now well recognized. Despite this, there is limited data on the effect of anti-osteoporotic therapies on AEDs-induced bone loss. Both phenytoin (PHT) and sodium valproate (SVP) inhibit human aromatase enzyme and stimulate microsomal catabolism of oestrogens. Estrogen deficiency states are known to reduce the deposition of transforming growth factor-β (TGF-β3), a bone matrix protein, having anti-osteoclastic property. Thus, an attempt was made to investigate the effect of raloxifene, a selective oestrogen receptor modulator, in comparison with CVD supplementation, on PHT and SVP-induced alterations in bone in mice. Further, the effect of raloxifene on seizures and on the antiepileptic efficacy of AEDs was also investigated. Swiss strains of female mice were treated with PHT (35 mg/kg, p.o.) and SVP (300 mg/kg, p.o.) for 120 days to induce bone loss as evidenced by reduced bone mineral density (BMD) and altered bone turnover markers in lumbar bones (alkaline phosphatase, tartarate resistant acid phosphatase, hydroxyproline) and urine (calcium). The bone loss was accompanied by reduced serum estradiol levels and bone TGF-β3 content. Preventive and curative treatment with raloxifene ameliorated bony alterations and was more effective than CVD. Deprived estrogen levels (that in turn reduced lumbar TGF-β3 content) following PHT and SVP, thus, might represent one of the various mechanisms of AEDs-induced bone loss. Raloxifene preserved the bony changes without interfering with their antiepileptic efficacy, and hence raloxifene could be a potential therapeutic option in the management of PHT and SVP-induced bone disease if clinically approved.

Keywords: antiepileptic drugs, osteoporosis, raloxifene, TGF-β3

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Authors: Jie Gao

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The combination of chemotherapy with gene therapy is highly effective in cancer therapy. To achieve combined therapeutic effects in human gastric cancer over expressing EGFR, we developed targeted LPD (liposome-polycation-DNA complex) conjugated with anti-EGFR (epidermal growth factor receptor) Fab’ for co-delivery of doxorubicin (DOX) and ribonucleotide reductase M2 (RRM2) siRNA (DOX-RRM2-TLPD). The results showed that EGFR was over expressed in several gastric cancer cell lines and gastric cancer tissues. Gene Expression Omnibus (GEO) results showed that RRM2 expression was significantly higher in gastric cancer than in non-gastric cancer tissue, and RRM2 siRNA inhibited the proliferation of several gastric cancer cells, indicating that RRM2 is a candidate target for gastric cancer therapy. Confocal studies and flow cytometry showed that DOX-RRM2-TLPD delivered DOX and RRM2 siRNA to EGFR over expressing gastric cancer cells specifically and efficiently both in vitro and in vivo, resulting in enhanced therapeutic effects (cytotoxicity and apoptosis) compared with single-drug loaded or non-targeted controls, including DOX-NC-TLPD (targeted LPD co-delivering DOX and negative control siRNA), RRM2-TLPD (targeted LPD delivering RRM2 siRNA) and DOX-RRM2-NTLPD (non-targeted LPD co-delivering DOX and RRM2 siRNA). The in vivo antitumor assay showed that the average weight of the gastric cancer in mice treated with DOX-RRM2-TLPD was significantly lighter than that of mice treated with other controls. DOX-RRM2-TLPD represents an effective approach for combined therapy of gastric cancer over expressing EGFR.

Keywords: gene therapy, chemotherapy, immunoliposomes, gastric cancer

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Authors: Xiaoyang Zhao, Kaiying Wang

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The choice of stocking density in poultry farming is a potential way for determining welfare level of poultry. However, it is difficult to measure stocking densities in poultry farming because of a lot of variables such as species, age and weight, feeding way, house structure and geographical location in different broiler houses. A method was proposed in this paper to measure the differences of young broilers reared under different stocking densities by sound analysis. Vocalisations of broilers were recorded and analysed under different stocking densities to identify the relationship between sounds and stocking densities. Recordings were made continuously for three-week-old chickens in order to evaluate the variation of sounds emitted by the animals at the beginning. The experimental trial was carried out in an indoor reared broiler farm; the audio recording procedures lasted for 5 days. Broilers were divided into 5 groups, stocking density treatments were 8/m², 10/m², 12/m² (96birds/pen), 14/m² and 16/m², all conditions including ventilation and feed conditions were kept same except from stocking densities in every group. The recordings and analysis of sounds of chickens were made noninvasively. Sound recordings were manually analysed and labelled using sound analysis software: GoldWave Digital Audio Editor. After sound acquisition process, the Mel Frequency Cepstrum Coefficients (MFCC) was extracted from sound data, and the Support Vector Machine (SVM) was used as an early detector and classifier. This preliminary study, conducted in an indoor reared broiler farm shows that this method can be used to classify sounds of chickens under different densities economically (only a cheap microphone and recorder can be used), the classification accuracy is 85.7%. This method can predict the optimum stocking density of broilers with the complement of animal welfare indicators, animal productive indicators and so on.

Keywords: broiler, stocking density, poultry farming, sound monitoring, Mel Frequency Cepstrum Coefficients (MFCC), Support Vector Machine (SVM)

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Authors: M. A. Ojo, O. A. Ojo, A. I. Odine, A. Ogaji

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The study examined marginal productivity analysis of small scale yam and cassava farmers in Kogi State, Nigeria. Data used for the study were obtained from primary source using a multi-stage sampling technique with structured questionnaires administered to 150 randomly selected yam and cassava farmers from three Local Government Areas of the State. Description statistics, data envelopment analysis and Cobb-Douglas production function were used to analyze the data. The DEA result on the overall technical efficiency of the farmers showed that 40% of the sampled yam and cassava farmers in the study area were operating at frontier and optimum level of production with mean technical efficiency of 1.00. This implies that 60% of the yam and cassava farmers in the study area can still improve their level of efficiency through better utilization of available resources, given the current state of technology. The results of the Cobb-Douglas analysis of factors affecting the output of yam and cassava farmers showed that labour, planting materials, fertilizer and capital inputs positively and significantly affected the output of the yam and cassava farmers in the study area. The study further revealed that yam and cassava farms in the study area operated under increasing returns to scale. This result of marginal productivity analysis further showed that relatively efficient farms were more marginally productive in resource utilization This study also shows that estimating production functions without separating the farms to efficient and inefficient farms bias the parameter values obtained from such production function. It is therefore recommended that yam and cassava farmers in the study area should form cooperative societies so as to enable them have access to productive inputs that will enable them expand. Also, since using a single equation model for production function produces a bias parameter estimates as confirmed above, farms should, therefore, be decomposed into efficient and inefficient ones before production function estimation is done.

Keywords: marginal productivity, DEA, production function, Kogi state

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Authors: Ç. Gökçek-Saraç, Ş. Özen, N. Derin

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The N-methyl-D-aspartate (NMDA)-dependent pathway is the major intracellular signaling pathway implemented in both short- and long-term memory formation in the hippocampus which is the most studied brain structure because of its well documented role in learning and memory. However, little is known about the effects of RF-EMR exposure on NMDA receptor signaling pathway including activation of protein kinases, notably Ca²⁺/calmodulin-dependent protein kinase II alpha (CaMKIIα). The aim of the present study was to investigate the effects of acute and chronic 900 MHz RF-EMR exposure on both passive avoidance behaviour and hippocampal levels of CaMKIIα and its phosphorylated form (pCaMKIIα). Rats were divided into the following groups: Sham rats, and rats exposed to 900 MHz RF-EMR for 2 h/day for 1 week (acute group) or 10 weeks (chronic group), respectively. Passive avoidance task was used as a behavioural method. The hippocampal levels of selected kinases were measured using Western Blotting technique. The results of passive avoidance task showed that both acute and chronic exposure to 900 MHz RF-EMR can impair passive avoidance behaviour with minor effects on chronic group of rats. The analysis of western blot data of selected protein kinases demonstrated that hippocampal levels of CaMKIIα and pCaMKIIα were significantly higher in chronic group of rats as compared to acute groups. Taken together, these findings demonstrated that different duration times (1 week vs 10 weeks) of 900 MHz RF-EMR exposure have different effects on both passive avoidance behaviour of rats and hippocampal levels of selected protein kinases.

Keywords: hippocampus, protein kinase, rat, RF-EMR

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Authors: Indu Barwal, Shloka Thakur, Subhash C. Yadav

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The plant virus capsid protein based nanoparticles are extensively studied for their application in biomedical research for development of nanomedicines and drug delivery systems. We have developed a chimeric drug delivery system by controlled in vitro assembly of separately bioconjugated fluorescent dye (as reporting molecule), folic acid (as receptor binding biomolecule for targeted delivery) and doxorubicin (as anticancer drug) using modified EDC NHS chemistry on heterologously overexpressed (E. coli) capsid proteins of cowpea chlorotic mottle virus (CCMV). This chimeric vehicle was further encapsidated on gold nanoparticles (20nm) coated with 5≠ thiolated DNA probe to neutralize the positive charge of capsid proteins. This facilitates the in vitro assembly of modified capsid subunits on the gold nanoparticles to develop chimeric GNPs encapsidated targeted drug delivery system. The bioconjugation of functionalities, number of functionality on capsid subunits as well as virus like nanoparticles, structural stability and in vitro assembly were confirmed by SDS PAGE, relative absorbance, MALDI TOF, ESI-MS, Circular dichroism, intrinsic tryptophan fluorescence, zeta particle size analyzer and TEM imaging. This vehicle was stable at pH 4.0 to 8.0 suitable for many organelles targeting. This in vitro assembled chimeric plant virus like particles could be suitable for ideal drug delivery vehicles for subcutaneous cancer treatment and could be further modified for other type of cancer treatment by conjugating other functionalities (targeting, drug) on capsids.

Keywords: chimeric drug delivery vehicles, bioconjugated plant, virus, capsid

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Authors: Jeferson Brito Fernades, Breno Padovezi Rocha, Roger Augusto Rodrigues, Heraldo Luiz Giacheti

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The geotechnical projects demand the appropriate knowledge of soil characteristics and parameters. The determination of geotechnical soil parameters can be done by means of laboratory or in situ tests. In countries with tropical weather, like Brazil, unsaturated soils are very usual. In these soils, the soil suction has been recognized as an important stress state variable, which commands the geo-mechanical behavior. Triaxial and direct shear tests on saturated soils samples allow determine only the minimal soil shear strength, in other words, no suction contribution. This paper briefly describes the triaxial test with controlled suction as well as discusses the influence of suction on the shear strength parameters of a lateritic tropical sandy soil from a Brazilian research site. In this site, a sample pit was excavated to retrieve disturbed and undisturbed soil blocks. The samples extracted from these blocks were tested in laboratory to represent the soil from 1.5, 3.0 and 5.0 m depth. The stress curves and shear strength envelopes determined by triaxial tests varying suction and confining pressure are presented and discussed. The water retention characteristics on this soil complement this analysis. In situ CPT tests were also carried out at this site in different seasons of the year. In this case, the soil suction profile was determined by means of the soil water retention. This extra information allowed assessing how soil suction also affected the CPT data and the shear strength parameters estimative via correlation. The major conclusions of this paper are: the undisturbed soil samples contracted before shearing and the soil shear strength increased hyperbolically with suction; and it was possible to assess how soil suction also influenced CPT test data based on the water content soil profile as well as the water retention curve. This study contributed with a better understanding of the shear strength parameters and the soil variability of a typical unsaturated tropical soil.

Keywords: site characterization, triaxial test, CPT, suction, variability

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Authors: Dwitya Elvira, Eryati Darwin

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Background: Graves’ disease (GD) is an autoimmune thyroid disease. Imbalance of Th1/Th2 cells and T-regulatory (Treg)/Th17 cells was thought to play pivotal role in the pathogenesis of GD. Treg FoxP3 produced TGF-β to maintain regulatory function, and Th17 cells produced IL-17 as cytokines that were thought in mediating several autoimmune diseases. The aim of this study is to assess the role of IL-17 and TGF-β in the pathogenesis of GD and to investigate its correlation with Thyroid Stimulating Hormone Receptor Antibody (TRAb) and Treg FoxP3 expression. Method: 30 GD patients and 27 age and sex-matched controls were enrolled in this study. Diagnosis of GD was based on clinical and biochemical of GD. Serum IL-17, TGF-β, TRAb, and FoxP3 were measured by enzyme-linked immunosorbent assay (ELISA). Data were analyzed by using SPSS 21.0 (SPSS Inc.). Spearman rank correlation test was used for assessment of correlation. The statistical significance was accepted as P<0.05. Result: There was no significant correlation between IL-17 and TGF-β serum with expression of FoxP3 level in GD, but there was significant correlation between TGF-β and TRAb serum level (P<0.05). Serum levels of IL-17 and TGF-β were found to be elevated in patient group compared to control, where mean values of IL-17 were 14.43±2.15 pg/mL and TGF-β were 10.44±3.19 pg/mL in patients group; and in control group, level of IL-17 were 7.1±1.45 pg/mL and TGF-β were 4.95±1.35 pg/mL. Conclusion: Serum Il-17 and TGF-β were elevated in GD patients that reflect the role of inflammatory and regulatory cytokines activation in pathogenesis of GD. There was significant correlation between TGF-β and TRAb, revealing that Treg cytokines may play a role in pathogenesis of GD.

Keywords: IL-17, TGF-B, FoxP3, TRAb, Graves’ disease

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Authors: Ramasamy Tamizhselvi, Leema George, Madhav Bhatia

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We have earlier shown that mouse pancreatic acinar cells produce hydrogen sulfide (H2S) and play a role in the pathogenesis of acute pancreatitis. This study is to determine the effect of H2S on TLR4 mediated innate immune signaling in acute pancreatitis via substance P (SP). Male Swiss mice were treated with hourly intraperitoneal injection of caerulein (50μg/kg) for 10 hour. DL-propargylglycine (PAG) (100 mg/kg i.p.), an inhibitor of H2S formation was administered 1h after the induction of acute pancreatitis. Pancreatic acinar cells from male Swiss mice were incubated with or without caerulein (10–7 M for 60 min) and CP-96345 (NK1R inhibitor). To better understand the effect of H2S in inflammation, acinar cells were stimulated with caerulein after addition of H2S donor, NaHS. In addition, caerulein treated pancreatic acinar cells were pretreated with PAG (30 µM), for 1h. H2S inhibitor, PAG, eliminated TLR4, IRAK4, TRAF6 and NF-kB levels in an in vitro and in vivo model of caerulein-induced acute pancreatitis. PPTA gene deletion reduced TLR4, MyD88, IRAK4, TRAF6, adhesion molecules and NF-kB in caerulein treated pancreatic acinar cells whereas administration of NaHS resulted in further rise in TLR4 and NF-kB levels in caerulein treated pancreatic acinar cells. In addition, acini isolated from mice and treated with PPTA gene receptor NK1R antagonist CP96345 did not exhibit further increase in TLR4, IRAK4, TRAF6, adhesion molecules and NF-kB levels after NaHS pretreatment. The present findings show for the first time that in acute pancreatitis, H2S up-regulates TLR4 pathway and NF-kB via substance P.

Keywords: preprotachykinin-A gene, H2S, TLR4, acute pancreatitis

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Authors: Najeeb Ullah Khan

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Background: The receptor activator NF-κβ ligand (RANKL) and Osteoprotegerin (OPG) polymorphisms have been associated with the progression of breast cancer to bone metastasis. Here, we aimed to investigate the association of RANKL and OPG gene polymorphism with breast to bone metastasis in the Pashtun population, Pakistan. Methods: Genomic DNA was obtained from all the study subjects (106 breast cancer, 58 breast to bone metastasis, and 51 healthy controls). RANKL (rs9533156) and OPG (rs2073618, rs3102735) polymorphisms were genotyped using Tetra-ARMS PCR. Results: Our results indicated that the frequencies of OPG (rs3102735) risk allele and genotypes carrying risk allele in breast cancer vs healthy control (C- p=0.005; CC- p=0.0208; TC- p=0.0181), bone metastasis vs healthy control (C- p=0.0211; CC- p=0.0153; TC- p=0.0775), and breast cancer vs breast to bone metastasis (C- p=0.0001; CC- p=0.0001; TC- p=0.001) were found significantly associated with disease risk. However, there was no significant association observed for OPG (rs2073618) risk allele and risk allele containing genotypes in all study groups. Similarly, RANKL (rs9533156) risk alleles and corresponding genotypes in breast cancer vs healthy control (C- p=0.0001; CC- p=0.0001; TC- p=0.0084), bone metastasis vs healthy control (C- p=0.0001; CC- p=0.0001; TC- p=0.5593), and breast cancer vs breast to bone metastasis (C- p=0.0185; CC- p=0.6077; TC- p=0.1436) showed significant association except for the risk allele carrying genotypes in breast cancer to bone metastasis (TC, p=0.1436; CC, p=0.6077). Conclusion: OPG (rs3102735) and RANKL (rs9533156) showed significant association with breast to bone metastasis, while OPG (rs2073618) didn’t show a significant association with breast to bone metastasis in Pashtun population of Pakistan. However, more investigation will be required to disseminate the results while gene sequencing or whole-exome sequencing.

Keywords: breast cancer, bone metastasis, OPG, RANKL, polymorphism

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