Search results for: adjuvant induced arthritis

Authors: Dina Kuttah

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It is well known that recycling of by-product materials saves natural resources, reduces by-product volumes, and reduces the need for virgin materials. The steel industry produces a myriad of metal components for industrial chains, which in turn generates mineral discarded sand molds. Although these sands are clean before their use, after casting, they may contain contaminants. Therefore, huge quantities of excess by-product foundry sand (BFS) end up occupying large volumes in landfills. In Sweden, approximately 200000 tonnes of excess BFS end up in landfills. The transportation and construction industries have the greatest potential for reuse by-products because they use vast quantities of earthen materials annually. Accordingly, experimental work has been undertaken to evaluate the possible use of two chosen BFS from two Swedish foundries in a conventional Swedish asphalt mixture. The experimental procedure of this research has focused on the dosage, environmental and technical properties of the same mixture type ABT 11 and the same bitumen (160/220) but at different replacement proportions of the conventional fine sand with the two BFS. The environmental requirements, in addition to the technical requirements, namely, void ratio, static indirect tensile strength ratio, and resilient modulus before and after moisture-induced sensitivity tests of the asphalt mixtures, have been investigated in the current study. The test results demonstrated that the BFS from both foundries can be incorporated in the selected asphalt mixture at specified replacement proportions of the conventional fine sand fraction 0-2 mm, as discussed in the paper.

Keywords: asphalt mixtures, by-product foundry sand, indirect tensile strength, moisture induced sensitivity tests, resilient modulus

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Authors: Gizaw Mamo Gebeyehu, Marianna Pap, Geza Makkai, Tibor Z. Janosi, Shima Rashidian, Tibor A. Rauch

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Sepsis poses a significant global health threat, necessitating extensive exploration of indicators tied to its pathological mechanisms and multi-organ dysfunction. While murine studies have shed light on sepsis, the intricate cellular and molecular landscape in human sepsis remains enigmatic. Exploring the influence of activated monocyte-derived exosomes in sepsis sheds light on a promising pathway for understanding the intricate cellular and molecular mechanisms involved in this condition in humans. In sepsis, exosome-borne mRNA and miRNA orchestrate immune response gene expression in recipient cells. Yet, the specifics of exosome-mediated cell-to-cell communication, especially how mRNA cargoes modulate gene expression in recipient cells, remain poorly understood. This study aims to elucidate the precise molecular pathways through which exosomal mRNA cargo, particularly MAFB, contributes to the developing sepsis-induced molecular aberrations in liver tissues, employing rigorously defined cell culture conditions. THP-1 cells were treated with LPS to induce changes in exosomal RNA profiles. Exosomes were isolated and characterized using microscopy and mass spectrometry. RNA was extracted from exosomes and sequenced. The most abundant exosomal mRNAs were subjected to GO analysis for functional annotation analysis and KEGG database analysis to identify the involved enriched pathways. PCR (Polymerase Chain Reaction), RNA sequencing, and Western blotting were involved to analyze changes in gene expression, protein levels, and signaling pathways within the liver cells( HepG2) after exposure to exosomal MAFB. This study pinpoints exosomal MAFB as a potential key regulator linked to liver cell damage during sepsis, along with associated genes (miR155HG, H3F3A, and possibly JARD2) forming a crucial molecular pathway contributing to liver cell injury, Together, these elements indicate a vital molecular pathway that plays a significant role in the emergence of liver cell injury during sepsis.. These findings suggest the importance of further research on these components for potential therapeutic interventions in managing acute liver damage in sepsis.

Keywords: sepsis, exososome, exosomal MAFB, LPS-induced THP-1 cells, RNA profiles, sepsis-triggered liver injury

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Authors: Alex Kiselyov, Suehyun Cho, Darrell Harrington; Florent Cros, Olin Palmer, John Caputo, Michael Kardosh, Eran Oren, William Loudon, Michael Shpigelmacher

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Despite the most aggressive surgical and adjuvant therapeutic strategies, treatment of both pediatric and adult brainstem tumors remains problematic. Novel strategies, including targeted biologics, immunotherapy, and specialized delivery systems such as convection-enhanced delivery (CED), have been proposed. While some of these novel treatments are entering phase I trials, the field is still in need of treatment(s) that exhibits dramatically enhanced potency with optimal therapeutic ratio. Bionaut Labs has developed a modular microrobotic platform for performing localized delivery of diverse therapeutics in vivo. Our biocompatible particles (Bionauts™) are externally propelled and visualized in real-time. Bionauts™ are specifically designed to enhance the effect of radiation therapy via anatomically precise delivery of a radiosensitizing agent, as exemplified by temozolomide (TMZ) and Avastin™ to the brainstem gliomas of diverse origin. The treatment protocol is designed to furnish a better therapeutic outcome due to the localized (vs systemic) delivery of the drug to the neoplastic lesion(s) for use as a synergistic combination of radiation and radiosensitizing agent. In addition, the procedure is minimally invasive and is expected to be appropriate for both adult and pediatric patients. Current progress, including platform optimization, selection of the lead radiosensitizer as well as in vivo safety studies of the Bionauts™ in large animals, specifically the spine and the brain of porcine and ovine models, will be discussed.

Keywords: Bionaut, brainstem, glioma, local delivery, micro-robot, radiosensitizer

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Authors: Antonis Elia, Theo Loizou, Gladys Onambele-Pearson, Matthew Barlow, Georgina Stebbings

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Hypoxic conditions have been reported to enhance red blood cell production in both acclimatised low-landers and altitude adapted populations. This process is mediated by the erythropoietin hormone, which is released predominantly by the hypoxic kidney. A higher haemoglobin concentration was previously reported in elite breath-hold divers when compared to elite-skiers and untrained individuals. Therefore, the present study aimed to investigate whether apnoea induced hypoxia could induce a significant increase in serum erythropoietin concentration in recreational breath-hold divers which would provide an explanation to the higher haemoglobin levels observed in elite breath-hold divers. Identifying whether apnoea induced hypoxia induces a significant increase in serum erythropoietin might suggest that apnoea can be used as an alternative acclimatisation method to high altitude exposure. Seven healthy, recreational male breath-hold divers performed two sets of five 180 second breath-holds with a ten-minute supine rest between each set and a two-minute seated rest between each apnoea. During each breath-hold, participant’s heart rate and peripheral oxygen saturation levels were recorded every subsequent 10 seconds until the end of the 180 second breath-hold. After each 180 second breath-hold a capillary blood sample was collected from the finger to identify circulating haemoglobin levels. Following completion of the apnoeic protocol, three blood samples were collected at 30, 90 and 180 minutes to measure circulating erythropoietin levels. A significant interaction between erythropoietin and time was observed (F(3,18)= 4.72, p < 0.001), with significant increases in erythropoietin evident at 30 (t(6)= -5.035, p < 0.0590 (t(6)= -6.162, p < 0.05) and 180 (t(6)= - 7.232, p < 0.001) minutes post the last apnoea when compared to baseline. Corresponding average increases when compared to baseline were 16% at 30, 23% at 90 and 40% at 180 minutes post the last apnoea. A significant interaction between haemoglobin and time was observed (F(78,84)= 20.814, p < 0.001), with significant increases in haemoglobin evident at the fifth (t(29)= -1.124, p < 0.001), ninth (t(29)= -1.357, p < 0.001) and tenth (t(29)= -1.211, p < 0.05) apnoeas when compared to baseline. A significant interaction between peripheral oxygen saturation and time was observed (F(10,60)= 408.23, p < 0.001). The present study demonstrates that a series of ten 180 second breath-holds is sufficient to induce a significant increase in the circulating erythropoietin concentration of recreational breath hold divers. These observations may suggest that apnoea induced hypoxia may be used as an alternative acclimatisation method to high altitude exposure.

Keywords: apnoea, breath-holding, diving reflex, erythropoietin, haemoglobin

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Authors: Tamer M. Shehata, Heba S. Elsewedy, Mashel Al Dosary, Alaa Elshehry, Mohamed A. Khedr, Maged E. Mohamed

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Objective: 2,4-Dichlorophenoxy acetic acid (2,4-D) is a well-known herbicide widely used as a weed killer. Recently, 2,4-D was rediscovered as a new anti-inflammatory agent through in silico as well as in-vivo experiments. However, poor solubility of 2,4-D could represent a problems during pharmaceutical development in addition to lower bioavailability. Solid dispersion (SD) refers to a group of solid products consisting of at least two different components, usually a hydrophobic drug and hydrophilic matrix. It is well known technique for enhancing drug solubility. Therefore, selecting SD as a tool for enhancing 2,4-D could be of great interest to the formulator. Method: In our project, several polymers were investigated (such as PEG, HPMC, citric acid and others) in addition to drug polymer ratios and its effect on solubility. Evaluation of drug polymer interaction was investigated through both Fourier Transform Infrared (FTIR) and Differential Scanning Calorimetry (DSC). Finally, in-vivo evaluation was performed for the best selected preparation through inflammatory response of rat induce hind paw. Results: Results indicated that, citric acid 2,4-D and in ratio of 0.75 : 1 showed modified the dissolution profile of the drug. The FTIR resltes indicated no significant chemical interaction, however DSC showed shifting of the drug melting point. Finally, Carragenan induced rat hind paw edema showed significant reduction of the drug solid dispersion in comparison to the pure drug, indicating rapid and complete absorption of the drug in solid dispersion form. Conclusion: Solid dispersion technology can be utilized efficiently to enhance the solubility of 2,4-D.

Keywords: solid dispersion, 2, 4-D solubility, carragenan induced edema

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Authors: Olga Shapovalova, Vladimir Vinogradov

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Among many different sol – gel matrices only alumina can be successfully parenteral injected in the human body. And this is not surprising, because boehmite (aluminium oxyhydroxide) is the metal oxide approved by FDA and EMA for intravenous and intramuscular administrations, and also has been using for a longtime as adjuvant for producing of many modern vaccines. In our earlier study, it has been shown, that denaturation temperature of enzymes entrapped in sol-gel boehmite matrix increases for 30 – 60 °С with preserving of initial activity. It makes such matrices more attractive for long-term storage of non-stable drugs. In current work we present ultrasound-assisted sol-gel synthesis of nano-boehmite. This method provides bio-friendly, very stable, highly homogeneous alumina sol with using only water and aluminium isopropoxide as a precursor. Many parameters of the synthesis were studied in details: time of ultrasound treatment, US frequency, surface area, pore and nanoparticle size, zeta potential and others. Here we investigated the dependence of stability of colloidal sols and textural properties of the final composites as a function of the time of ultrasonic treatment. Chosen ultrasonic treatment time was between 30 and 180 minutes. Surface area, average pore diameter and total pore volume of the final composites were measured by surface and pore size analyzer Nova 1200 Quntachrome. It was shown that the matrices with ultrasonic treatment time equal to 90 minutes have the biggest surface area 431 ± 24 m2/g. On the other had such matrices have a smaller stability in comparison with the samples with ultrasonic treatment time equal to 120 minutes that have the surface area 390 ± 21 m2/g. It was shown that the stable sols could be formed only after 120 minutes of ultrasonic treatment, otherwise the white precipitate of boehmite is formed. We conclude that the optimal ultrasonic treatment time is 120 minutes.

Keywords: boehmite matrix, stabilisation, ultrasound-assisted sol-gel synthesis

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Authors: Ngawang Tsering

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Traditional Tibetan medicine is primarily focused on promoting health and keeping away diseases from its unique in prescribing specific diet and lifestyle. The prevalence of chronic diseases has been rising day by day and kills a number of people due to the lack of proper nutritional design in modern times. According to traditional Tibetan medicine, chronic diseases such as diabetes, cancer, cardiovascular diseases, respiratory diseases, and arthritis are heavily associated with an unwholesome diet and inappropriate lifestyles. Diet and lifestyles are the two main conditions of diseases and healthy life. The prevalence of chronic diseases is one of the challenges, with massive economic impact and expensive health issues. Though chronic diseases are challenges, it has a solution in the preventive measurements by using proper nutrition design based on traditional Tibetan medicine. Until today, it is hard to evaluate whether traditional Tibetan medicine nutrition strategy could play a major role in preventive measurement as of the lack of current research evidence. However, compared with modern nutrition, it has an exclusive valuable concept, such as a holistic way and diet or nutrition recommendation based on different aspects. Traditional Tibetan medicine is one of the oldest ancient existing medical systems known as Sowa Rigpa (Science of Healing) highlights different aspects of dietetics and nutrition, namely geographical, seasonal, age, personality, emotional, food combination, the process of individual metabolism, potency, and amount of food. This article offers a critical perspective on the preventive measurement against chronic diseases through nutrition design using traditional Tibetan medicine and also needs attention for a deeper understanding of traditional Tibetan medicine in the modern world.

Keywords: traditional Tibetan medicine, nutrition, chronic diseases, preventive measurement, holistic approach, integrative

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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: Manendra Singh Parihar, Sandip Ghosh Chowdhury

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Austenitic stainless steels are widely used and give a good combination of properties. When this steel is plastically deformed, a phase transformation of the metastable Face Centred Cubic Austenite to the stable Body Centred Cubic (α’) or to the Hexagonal close packed (ԑ) martensite may occur, leading to the enhancement in the mechanical properties like strength. The work was based on variant selection and corresponding texture analysis for the strain induced martensitic transformation during deformation of the parent austenite FCC phase to form the product HCP and the BCC martensite phases separately, obeying their respective orientation relationships. The automated method for reconstruction of the parent phase orientation using the EBSD data of the product phase orientation is done using the MATLAB and TSL-OIM software. The method of triplets was used which involves the formation of a triplet of neighboring product grains having a common variant and linking them using a misorientation-based criterion. This led to the proper reconstruction of the pre-transformation phase orientation data and thus to its microstructure and texture. The computational speed of current method is better compared to the previously used methods of reconstruction. The reconstruction of austenite from ԑ and α’ martensite was carried out for multiple samples and their IPF images, pole figures, inverse pole figures and ODFs were compared. Similar type of results was observed for all samples. The comparison gives the idea for estimating the correct sequence of the transformation i.e. γ → ε → α’ or γ → α’, during deformation of AISI 304 austenitic stainless steel.

Keywords: variant selection, reconstruction, EBSD, austenitic stainless steel, martensitic transformation

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Authors: Sohair Hassan, Olfat Hammam, Sahar Hussein, Wessam Magdi

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Objective: Acute liver failure (ALF) is a clinical condition with an unclear history of pathophysiology, making it a challenging task for scientists to reverse the disease in its initial phase and to help the liver re-function customary: this study aimed to estimate the hepatoprotective effects of Punica granatum Lpeel and Pistacia atlantica leaves as a multi-rich antioxidants ingredients either in their normal and/or in their nanoforms against thioacetamide induced acute liver failure in a rodent model. Method: Male Wistar rats (n=60) were divided into six equal groups, the first group employed as a control; The second group administered a dose of 350 mg /Kg/ b.w of thioacetamide (TAA)-IP, from the third to the sixth group received TAA + [2mls / 100 g b.w/d] of aqueous extracts of Punica granatum L and Pistacia atlantica either in their normal and/or Nano forms consecutively for (14 days) Results: Recorded significant elevation in liver enzymes, lipid profiles, LPO (p= 0.05) and NO with a marked significant decrease in GSH and SOD accompanied by an elevation in inflammatory cytokine (IL6, TNF-α, and AFP) in addition to a noticeable increase in HSP70 level & degradation in DNA respectively in TAA challenged group. However significant and subsequent amelioration of most of the impaired markers was observed with ip nano treatment of both extracts. Conclusion: The current results highlighted the high performance of both plant nano extracts and their hepatoprotective impact and their possible therapeutic role in the amelioration of TAA induced acute liver failure in experimental animals.

Keywords: acute liver failure HPLC, IL6, nano extracts, thioacetamide, TNF-α

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Authors: M. A. García, J. Vinolas, A. Hernando

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Steel is nowadays one of the most important structural materials because of its outstanding mechanical properties. Therefore, in order to look for a sustainable economic model and to optimize the use of extensive resources, new methods to monitor and prevent failure of steel-based facilities are required. The classical mechanical tests, as for instance building tasting, are invasive and destructive. Moreover, for facilities where the steel element is embedded, (as reinforced concrete) these techniques are directly non applicable. Hence, non-invasive monitoring techniques to prevent failure, without altering the structural properties of the elements are required. Among them, electromagnetic methods are particularly suitable for non-invasive inspection of the mechanical state of steel-based elements. The magnetoelastic coupling effects induce a modification of the electromagnetic properties of an element upon applied stress. Since most steels are ferromagnetic because of their large Fe content, it is possible to inspect their structure and state in a non-invasive way. We present here a distinct electromagnetic method for contactless evaluation of internal stress in steel-based elements. In particular, this method relies on measuring the magnetic induction between two coils with the steel specimen in between them. We found that the alteration of electromagnetic properties of the steel specimen induced by applied stress-induced changes in the induction allowed us to detect stress well below half of the elastic limit of the material. Hence, it represents an outstanding non-invasive method to prevent failure in steel-based facilities. We here describe the theoretical model, present experimental results to validate it and finally we show a practical application for detection of stress and inhomogeneities in train railways.

Keywords: magnetoelastic, magnetic induction, mechanical stress, steel

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Authors: Feng-Sheng Wang, Chao-Ting Cheng

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Developing a drug from conception to launch is costly and time-consuming. Computer-aided methods can reduce research costs and accelerate the development process during the early drug discovery and development stages. This study developed a fuzzy multi-objective hierarchical optimization framework for identifying potential anticancer targets in a metabolic model. First, RNA-seq expression data of colorectal cancer samples and their healthy counterparts were used to reconstruct tissue-specific genome-scale metabolic models. The aim of the optimization framework was to identify anticancer targets that lead to cancer cell death and evaluate metabolic flux perturbations in normal cells that have been caused by cancer treatment. Four objectives were established in the optimization framework to evaluate the mortality of cancer cells for treatment and to minimize side effects causing toxicity-induced tumorigenesis on normal cells and smaller metabolic perturbations. Through fuzzy set theory, a multiobjective optimization problem was converted into a trilevel maximizing decision-making (MDM) problem. The applied nested hybrid differential evolution was applied to solve the trilevel MDM problem using two nutrient media to identify anticancer targets in the genome-scale metabolic model of colorectal cancer, respectively. Using Dulbecco’s Modified Eagle Medium (DMEM), the computational results reveal that the identified anticancer targets were mostly involved in cholesterol biosynthesis, pyrimidine and purine metabolisms, glycerophospholipid biosynthetic pathway and sphingolipid pathway. However, using Ham’s medium, the genes involved in cholesterol biosynthesis were unidentifiable. A comparison of the uptake reactions for the DMEM and Ham’s medium revealed that no cholesterol uptake reaction was included in DMEM. Two additional media, i.e., a cholesterol uptake reaction was included in DMEM and excluded in HAM, were respectively used to investigate the relationship of tumor cell growth with nutrient components and anticancer target genes. The genes involved in the cholesterol biosynthesis were also revealed to be determinable if a cholesterol uptake reaction was not induced when the cells were in the culture medium. However, the genes involved in cholesterol biosynthesis became unidentifiable if such a reaction was induced.

Keywords: Cancer metabolism, genome-scale metabolic model, constraint-based model, multilevel optimization, fuzzy optimization, hybrid differential evolution

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Authors: Luminita Marin, Dalila Belei, Carmen Dumea

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Aggregation induced emission (AIE) is an intriguing optical phenomenon recently evidenced by Tang and his co-workers, for which aggregation works constructively in the improving of light emission. The AIE challenging phenomenon is quite opposite to the notorious aggregation caused quenching (ACQ) of light emission in the condensed phase, and comes in line with requirements of photonic and optoelectronic devices which need solid state emissive substrates. This paper reports a series of ten new aggregation induced emission (AIE) low molecular weight compounds based on triazole and pyridine-N-oxide heterocyclic units bonded by short flexible chains, obtained by a „click” chemistry reaction. The compounds present extremely weak luminescence in solution but strong light emission in solid state. To distinguish the influence of the crystallinity degree on the emission efficiency, the photophysical properties were explored by UV-vis and photoluminescence spectroscopy in solution, water suspension, amorphous and crystalline films. On the other hand, the compound morphology of the up mentioned states was monitored by dynamic light scattering, scanning electron microscopy, atomic force microscopy and polarized light microscopy methods. To further understand the structural design – photophysical properties relationship, single crystal X-ray diffraction on some understudy compounds was performed too. The UV-vis absorption spectra of the triazole water suspensions indicated a typical behaviour for nanoparticle formation, while the photoluminescence spectra revealed an emission intensity enhancement up to 921-fold higher of the crystalline films compared to solutions, clearly indicating an AIE behaviour. The compounds have the tendency to aggregate forming nano- and micro- crystals in shape of rose-like and fibres. The crystals integrity is kept due to the strong lateral intermolecular forces, while the absence of face-to-face forces explains the enhanced luminescence in crystalline state, in which the intramolecular rotations are restricted. The studied flexible triazoles draw attention to a new structural design in which small biologically friendly luminophore units are linked together by small flexible chains. This design enlarges the variety of the AIE luminogens to the flexible molecules, guiding further efforts in development of new AIE structures for appropriate applications, the biological ones being especially envisaged.

Keywords: aggregation induced emission, pyridine-N-oxide, triazole

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Authors: Lila D. Sigdel, Chin J. Leo, Samanthika Liyanapathirana, Pan Hu, Minghao Lu

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Integral bridges are a class of bridges with integral or semi-integral abutments, designed without expansion joints in the bridge deck of the superstructure. Integral bridges are economical alternatives to conventional jointed bridges with lower maintenance costs and greater durability, thereby improving social and economic stability for the community. Integral bridges have also been proven to be effective in lowering the overall construction cost compared to the conventional type of bridges. However, there is significant uncertainty related to the design and analysis of integral bridges in response to cyclic thermal movements induced due to deck expansion and contraction. The cyclic thermal movements of the abutments increase the lateral earth pressures on the abutment and its foundation, leading to soil settlement and heaving of the backfill soil. Thus, the primary objective of this paper is to investigate the soil-abutment interaction under the cyclic translational movement of the abutment. Results from five experiments conducted to simulate different magnitudes of cyclic translational movements of abutments induced by thermal changes are presented, focusing on lateral earth pressure development at the abutment-soil interface. Test results show that the cycle number and magnitude of cyclic translational movements have significant effects on the escalation of lateral earth pressures. Experimentally observed earth pressure distributions behind the integral abutment were compared with the current design approaches, which shows that the most of the practices has under predicted the lateral earth pressure.

Keywords: integral bridge, cyclic thermal movement, lateral earth pressure, soil-structure interaction

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Authors: J. O. Ezekwesili-Ofili, L. I. Okorafor, S. C. Nsofor

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Diabetes mellitus is a carbohydrate metabolism disorder due to an absolute or relative deficiency of insulin secretion, action or both. Many known hypoglycaemic drugs are known to produce serious side effects. However, the search for safer and more effective agents has shifted to plant products, including foods and spices. One of such is the rhizome of Curcuma longa or turmeric, which is a spice with high medicinal value. A drawback in the use of C. longa is the poor bioavailability of curcumin, the active ingredient. It has been reported that piperine, an alkaloid present in peppers increases the bioavailability of curcumin. This work therefore investigated the hypoglycaemic and antioxidant effects of ethanolic extract of C. longa rhizomes, alone and with two pepper adjuvants in alloxan-induced diabetic rats. A total of 48 rats were divided into 6 groups of 8 rats each. Groups A–E were induced with diabetes using 150mg/kg body weight of alloxan monohydrate, while group F was normoglycaemic: Group A: Diabetic; fed with 400 mg/g body weight of turmeric extract; group B: Diabetic, fed with 400 mg/kg b. w. and 200mg/kg b. w of ethanolic extract of seeds of Piper guinensee; group C: Diabetic, fed with 400 mg/kg b. w. and 200 mg /kg b. w. of ethanolic extract of seeds of Capsicum annum var cameroun, group D: Diabetic, treated with standard drug, glibenclamide (0.3mg/kg body weight), group E: Diabetic; no treatment i.e. Positive control and group F: non diabetic, no treatment i.e. Negative control. Blood glucose levels were monitored for 14 days using a glucometer. The levels of the antioxidant enzymes; glutathione peroxidase, catalase and superoxide dismutase were also assayed in serum. The ethanolic extracts of C. longa rhizomes at the dose given (400 mg/kg b. w) significantly reduced the blood glucose levels of the diabetic rats (p<0.05) comparable to the standard drug. Co administration of extract of the peppers did not significantly increase the efficiency of the extract, although C. annum var cameroun showed greater effect, though not significantly. The antioxidant effect of the extract was significant in diabetic rats. The use of piperine-containing peppers enhanced the antioxidant effect. Phytochemical analyses of the ethanolic extract of C. longa showed the presence of alkaloids, flavonoids, steroids, saponins, tannins, glycosides, and terpenoids. These results suggest that the ethanolic extract of C. longa had antidiabetic with antioxidant effects and could thus be of benefit in the treatment and management of diabetes as well as ameliorate pro-oxidant effects that may lead to diabetic complications. However, while the addition of piperine did not affect the antidiabetic effect of C. longa, the antioxidant effect was greatly enhanced.

Keywords: antioxidant, Curcuma longa rhizome, hypoglycaemic, pepper adjuvants, piperine

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Authors: Neha Singh, Anuj Ranjan, Tanu Jindal

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Over the last decade, the exponential growth of mobile communication has been accompanied by a parallel increase in density of electromagnetic fields (EMF). The continued expansion of mobile phone usage raises important questions as EMF, especially radio frequency (RF), have long been suspected of having biological effects. In the present experiments, we studied the effects of RF-EMF on cell death (apoptosis) and DNA damage of a well- tested biological model, Drosophila melanogaster exposed to 2400 MHz frequency for different time duration i.e. 2 hrs, 4 hrs, 6 hrs,8 hrs, 10 hrs, and 12 hrs each day for five continuous days in ambient temperature and humidity conditions inside an exposure chamber. The flies were grouped into control, sham-exposed, and exposed with 100 flies in each group. In this study, well-known techniques like Comet Assay and TUNEL (Terminal deoxynucleotide transferase dUTP Nick End Labeling) Assay were used to detect DNA damage and for apoptosis studies, respectively. Experiments results showed DNA damage in the brain cells of Drosophila which increases as the duration of exposure increases when observed under the observed when we compared results of control, sham-exposed, and exposed group which indicates that EMF radiation-induced stress in the organism that leads to DNA damage and cell death. The process of apoptosis and mutation follows similar pathway for all eukaryotic cells; therefore, studying apoptosis and genotoxicity in Drosophila makes similar relevance for human beings as well.

Keywords: cell death, apoptosis, Comet Assay, DNA damage, Drosophila, electromagnetic fields, EMF, radio frequency, RF, TUNEL assay

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Authors: Wan Liu, Haibo Wang, Cathy Huang, Zhiwu Tan, Zhiwei Chen

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The tremendous diversity of HIV-1 has been a major challenge for an effective AIDS vaccine development. Mosaic approach presents the potential for vaccine design aiming for global protection. The mosaic antigen of HIV-1 Gag allows antigenic breadth for vaccine-elicited immune response against a wider spectrum of viral strains. However, the enhancement of immune response using vaccines is dependent on the strategy used. Heterologous prime/boost regimen has been shown to elicit high levels of immune responses. Here, we investigated whether priming using plasmid DNA with electroporation followed by boosting with the live replication-competent modified vaccinia virus vector TianTan (MVTT) combined with the mosaic antigenic sequence could elicit a greater and broader antigen-specific response against HIV-1 Gag in mice. When compared to DNA or MVTT alone, or MVTT/MVTT group, DNA/MVTT group resulted in coincidentally high frequencies of broadly reactive, Gag-specific, polyfunctional, long-lived, and cytotoxic CD8+ T cells and increased anti-Gag antibody titer. Meanwhile, the vaccination could upregulate PD-1+, and Tim-3+ CD8+ T cell, myeloid-derived suppressive cells and Treg cells to balance the stronger immune response induced. Importantly, the prime/boost vaccination could help control the EcoHIV and mesothelioma AB1-gag challenge. The stronger protective Gag-specific immunity induced by a Mosaic DNA/MVTT vaccine corroborate the promise of the mosaic approach, and the potential of two acceptably safe vectors to enhance anti-HIV immunity and cancer prevention.

Keywords: DNA/MVTT vaccine, EcoHIV, mosaic antigen, mesothelioma AB1-gag

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Authors: Umara Nissar Rafiqi, Irum Gul, Nazima Nasrullah, Monica Saifi, Malik Z. Abdin

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Background: Stevia rebaudiana, a member of Asteraceae family is an important medicinal plant and produces a commercially used non-caloric natural sweetener, which is also an alternate herbal cure for diabetes. Steviol glycosides are the main sweetening compounds present in these plants. Secondary metabolites are crucial to the adaption of plants to the environment and its overcoming stress conditions. In agricultural procedures, the abiotic stresses like salinity, high metal toxicity and drought, in particular, are responsible for the majority of the reduction that differentiates yield potential from harvestable yield. Salt stress and heavy metal toxicity lead to increased production of reactive oxygen species (ROS). To avoid oxidative damage due to ROS and osmotic stress, plants have a system of anti-oxidant enzymes along with several stress induced enzymes. This helps in scavenging the ROS and relieve the osmotic stress in different cell compartments. However, whether stress induced toxicity modulates the activity of these enzymes in Stevia rebaudiana is poorly understood. Aim: The present study focussed on the effect of salinity, heavy metal toxicity (lead and mercury) on physiological traits and transcriptional profiling of Stevia rebaudiana. Method: Stevia rebaudiana plants were collected from the Central Institute of Medicinal and Aromatic plants (CIMAP), Patnagar, India and maintained under controlled conditions in a greenhouse at Hamdard University, Delhi, India. The plants were subjected to different concentrations of salt (0, 25, 50 and 75 mM respectively) and heavy metals, lead and mercury (0, 100, 200 and 300 µM respectively). The physiological traits such as shoot length, root numbers, leaf growth were evaluated. The samples were collected at different developmental stages and analysed for transcription profiling by RT-PCR. Transcriptional studies in stevia rebaudiana involves important antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), cytochrome P450 monooxygenase (CYP) and stress induced aquaporin (AQU), auxin repressed protein (ARP-1), Ndhc gene. The data was analysed using GraphPad Prism and expressed as mean ± SD. Result: Low salinity and lower metal toxicity did not affect the fresh weight of the plant. However, this was substantially decreased by 55% at high salinity and heavy metal treatment. With increasing salinity and heavy metal toxicity, the values of all studied physiological traits were significantly decreased. Chlorosis in treated plants was also observed which could be due to changes in Fe:Zn ratio. At low concentrations (upto 25 mM) of NaCl and heavy metals, we did not observe any significant difference in the gene expressions of treated plants compared to control plants. Interestingly, at high salt concentration and high metal toxicity, a significant increase in the expression profile of stress induced genes was observed in treated plants compared to control (p < 0.005). Conclusion: Stevia rebaudiana is tolerant to lower salt and heavy metal concentration. This study also suggests that with the increase in concentrations of salt and heavy metals, harvest yield of S. rebaudiana was hampered.

Keywords: Stevia rebaudiana, natural sweetener, salinity, heavy metal toxicity

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Authors: Ahmed A. Alghamdi

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Single-walled carbon nanotubes (SWCNTs) are an outstanding material for applications in thermoelectric power generation, nanoelectronics, electrochemical energy storage, photovoltaics, and light emission. They are ultra-lightweight and possess electrical as well as thermal conductivity, flexibility, and mechanical strength. SWCNT is applicable in water treatment, brine desalination, removal of heavy metal ions associated with pollutants, and oil-water separation. Carbon nanotube (CNT) is believed to tackle the trade-off issue between permeability, selectivity, and fouling issues in membrane filtration applications. Studying these CNT structures, as well as their interconnection in nanotechnology, assists in finding the precise position to be placed for water desalination. Reverse osmosis (RO) has been used globally for desalination, resulting in purified water. Thin film composite (TFC) membranes were utilized in the RO process for desalination. The sheet thickness increases the salt rejection and decreases the water flux when CNT is utilized as a support layer to this membrane. Thus, through a temperature-induced phase separation technique (TIPS), axially aligned SWCNT (AASWCNT) is fabricated, and its use enhances the salt rejection and water flux at short reaction times with a modified procedure. An evaluation was conducted and analogized with prior works in the literature, which exhibited that the prepared TFC membrane showed a better outcome.

Keywords: single-walled carbon nanotubes, thin film composite, axially aligned swcnt, temperature induced phase separation technique, reverse osmosis

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Authors: Manendra Singh Parihar, Sandip Ghosh Chowdhury

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Austenitic stainless steels are widely used and give a good combination of properties. When this steel is plastically deformed, a phase transformation of the metastable Face Centred Cubic Austenite to the stable Body Centred Cubic (α’) or to the Hexagonal close packed (ԑ) martensite may occur, leading to the enhancement in the mechanical properties like strength. The work was based on variant selection and corresponding texture analysis for the strain induced martensitic transformation during deformation of the parent austenite FCC phase to form the product HCP and the BCC martensite phases separately, obeying their respective orientation relationships. The automated method for reconstruction of the parent phase orientation using the EBSD data of the product phase orientation is done using the MATLAB and TSL-OIM software. The method of triplets was used which involves the formation of a triplet of neighboring product grains having a common variant and linking them using a misorientation-based criterion. This led to the proper reconstruction of the pre-transformation phase orientation data and thus to its micro structure and texture. The computational speed of current method is better compared to the previously used methods of reconstruction. The reconstruction of austenite from ԑ and α’ martensite was carried out for multiple samples and their IPF images, pole figures, inverse pole figures and ODFs were compared. Similar type of results was observed for all samples. The comparison gives the idea for estimating the correct sequence of the transformation i.e. γ → ε → α’ or γ → α’, during deformation of AISI 304 austenitic stainless steel.

Keywords: variant selection, reconstruction, EBSD, austenitic stainless steel, martensitic transformation

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Authors: Surbhi Aggarwal, Jaishree Paul

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Background: Role of GABA has been implicated in autoimmune diseases like multiple sclerosis, type1 diabetes and rheumatoid arthritis where they modulate the immune response but role in gut inflammation has not been defined. Ulcerative colitis (UC) and diarrhoeal predominant irritable bowel syndrome (IBS-D) both involve inflammation of gastrointestinal tract. UC is a chronic, relapsing and idiopathic inflammation of gut. IBS is a common functional gastrointestinal disorder characterised by abdominal pain, discomfort and alternating bowel habits. Mild inflammation is known to occur in IBS-D. Aim: Aim of this study was to investigate the role of GABA in UC as well as in IBS-D. Materials and methods: Blood and biopsy samples from UC, IBS-D and controls were collected. ELISA was used for measuring level of GABA in serum of UC, IBS-D and controls. RT-PCR analysis was done to determine GABAergic signal system in colon biopsy of UC, IBS-D and controls. RT-PCR was done to check the expression of proinflammatory cytokines. CurveExpert 1.4, Graphpad prism-6 software were used for data analysis. Statistical analysis was done by unpaired, two-way student`s t-test. All sets of data were represented as mean± SEM. A probability level of p < 0.05 was considered statistically significant. Results and conclusion: Significantly decreased level of GABA and altered GABAergic signal system was detected in UC and IBS-D as compared to controls. Significantly increased expression of proinflammatory cytokines was also determined in UC and IBS-D as compared to controls. Hence we conclude that insufficient level of GABA in UC and IBS-D leads to overproduction of proinflammatory cytokines which further contributes to inflammation. GABA may be used as a promising therapeutic target for treatment of gut inflammation or other inflammatory diseases.

Keywords: diarrheal predominant irritable bowel syndrome, γ-aminobutyric acid (GABA), inflammation, ulcerative colitis

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Authors: Roman Medvedev, Andrey Yakshin, Konstantin Nikolaev, Sergey Yakunin, Fred Bijkerk

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Multilayer structures are used as spectroscopic elements in fluorescence analysis. These serve the purpose of analyzing soft x-ray emission spectra of materials upon excitation by x-rays or electrons. The analysis then allows quantitative determination of the x-ray emitting elements in the materials. Shorter wavelength range for this application, below 2.5nm, can be covered by using short period multilayers, with a period of 2.5 nm and lower. Thus the detrimental effect on the reflectivity of morphological roughness between materials of the multilayers becomes increasingly pronounced. Ion beam polishing was previously shown to be effective in reducing roughness in some multilayer systems with Si. In this work, we explored W/Si multilayers with the period of 2.5 nm. Si layers were polishing by Ar ions, employing low energy ions, 100 and 80 eV, with the etched Si thickness being in the range 0.1 to 0.5 nm. CuK X-ray diffuse scattering measurements revealed a significant reduction in the diffused scattering in the polished multilayers. However, Grazing Incidence CuK X-ray showed only a marginal reduction of the overall roughness of the systems. Still, measurements of the structures with Grazing Incidence Small Angle X-ray scattering indicated that the vertical correlation length of roughness was strongly reduced in the polished multilayers. These results together suggest that polishing results in the reduction of the vertical propagation of roughness from layer to layer, while only slightly affecting the overall roughness. This phenomenon can be explained by ion-induced surface roughening inherently present in the ion polishing methods. Alternatively, ion-induced densification of thin Si films should also be considered. Finally, the reflectivity of 40% at 0.84 nm at grazing incidence of 9 degrees has been obtained in this work for W/Si multilayers. Analysis of the obtained results is expected to lead to further progress in reflectance.

Keywords: interface roughness, ion polishing, multilayer structures, W/Si

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Authors: A. Katsman, L. Bloch, Y. Etinger, Y. Kauffmann, B. Pokroy

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Various nanosized amorphous alumina thin films in the range of (2.4 - 63.1) nm were deposited onto amorphous carbon and amorphous Si3N4 membrane grids. Transmission electron microscopy (TEM), electron energy loss spectroscopy (EELS), X-ray photoelectron spectroscopy (XPS) and differential scanning calorimetry (DSC) techniques were used to probe the size effect on the short range order and the amorphous to crystalline phase transition temperature. It was found that the short-range order changes as a function of size: the fraction of tetrahedral Al sites is greater in thinner amorphous films. This result correlates with the change of amorphous alumina density with the film thickness demonstrated by the reflectivity experiments: the thinner amorphous films have the less density. These effects are discussed in terms of surface reconstruction of the amorphous alumina films. The average atomic binding energy in the thin film layer decreases with decease of the thickness, while the average O-Al interatomic distance increases. The reconstruction of amorphous alumina is induced by the surface reconstruction, and the short range order changes being dependent on the density. Decrease of the surface energy during reconstruction is the driving force of the alumina reconstruction (density change) followed by relaxation process (short range order change). The amorphous to crystalline phase transition temperature measured by DSC rises with the decrease in thickness from 997.6°C for 13.9 nm to 1020.4 °C for 2.7 nm thick. This effect was attributed to the different film densities: formation of nanovoids preceding and accompanying crystallization process influences the crystallization rate, and by these means, the temperature of crystallization peak.

Keywords: amorphous alumina, density, short range order, size effect

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Authors: Mukunda Upreti, Jill Storry, Rafael Björk, Emilie Louvet, Johan Normark, Sven Bergström

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Borrelia duttonii and most other relapsing fever species are Gram-negative bacteria which cause a blood borne infection characterized by the binding of bacterium to erythrocytes. The bacteria associate with two or more erythrocytes to form clusters of cells into rosettes. Rosetting is a major virulence factor and the mechanism is believed to facilitate persistence of bacteria in the circulatory system and the avoidance of host immune cells through masking or steric hindrance effects. However, the molecular mechanisms of rosette formation are still poorly understood. This study aims at determining the molecules involved in the rosette formation phenomenon. Fractionated serum, using different affinity purification methods, was investigated as a rosetting agent and IgG and at least one other serum components were needed for rosettes to form. An IgG titration curve demonstrated that IgG alone is not enough to restore rosette formation level to the level whole serum gives. IgG hydrolysis by IdeS ( Immunoglobulin G-degrading enzyme of Streptococcus pyogenes) and deglycosylation using N-Glycanase proved that the whole IgG molecule regardless of saccharide moieties is critical for Borrelia induced rosetting. Complement components C3 and C4 were also important serum molecules necessary to maintain optimum rosetting rates. The deactivation of complement network and serum depletion with C3 and C4 significantly reduced the rosette formation rate. The dependency of IgG and complement components also implied involvement of the complement receptor (CR1). Rosette formation test with Knops null RBC and sCR1 confirmed that CR1 is also part of Borrelia induced rosette formation.

Keywords: complement components C3 and C4, complement receptor 1, Immunoglobulin G, Knops null, Rosetting

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Authors: Asher John Mohan, Krishna K. L.

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Objectives: (1) To assess the extent of memory impairment induced by Phenytoin (PHT) at normal and reduced dose on temporal lobe epileptic mice. (2) To evaluate the protective effect of Levetiracetam (LEV) on aggravation of memory impairment in temporal lobe epileptic mice by PHT. Materials and Methods: Albino mice of either sex (n=36) were used for the study for a period of 64 days. Convulsions were induced by intraperitoneal administration of pilocarpine 280 mg/kg on every 6th day. Radial arm maze (RAM) was employed to evaluate the memory impairment activity on every 7th day. The anticonvulsant and memory impairment activity were assessed in PHT normal and reduced doses both alone and in combination with LEV. RAM error scores and convulsive scores were the parameters considered for this study. Brain acetylcholine esterase and glutamate were determined along with histopathological studies of frontal cortex. Results: Administration of PHT for 64 days on mice has shown aggravation of memory impairment activity on temporal lobe epileptic mice. Although the reduction in PHT dose was found to decrease the degree of memory impairment the same decreased the anticonvulsant potency. The combination with LEV not only brought about the correction of impaired memory but also replaced the loss of potency due to the reduction of the dose of the antiepileptic drug employed. These findings were confirmed with enzyme and neurotransmitter levels in addition to histopathological studies. Conclusion: This study thus builds a foundation in combining a nootropic anticonvulsant with an antiepileptic drug to curb the adverse effect of memory impairment associated with temporal lobe epilepsy. However further extensive research is a must for the practical incorporation of this approach into disease therapy.

Keywords: anti-epileptic drug, Phenytoin, memory impairment, Pilocarpine

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Authors: D. O. Miranda, L. R. Azevedo, J. F. C. Cordeiro, A. H. Dos Santos, S. F. Lisboa, F. S. Guimarães, G. S. Bisson

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Background: The Colorectal cancer (CRC) is one of the most common cancers and the fourth leading cause of cancer death in the world. The prevalence of psychiatric-disorders among CRC patients, mainly depression, is high, resulting in impaired quality of life and side effects of primary treatment. High levels of proinflammatory cytokines at tumor microenvironment is a feature of CRC and the literature suggests that those mediators could contribute to the development of psychiatric disorders. Nevertheless, the ability of tumor-associated biological processes to affect the central nervous system (CNS) has only recently been explored in the context of symptoms of depression and is still not well understood. Therefore, the aim of the present study was to test the hypothesis that depressive-like behavior in an experimental model of CCR induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) was correlated to proinflammatory profile in the periphery and in the brain. Methods: Colorectal carcinogenesis was induced in adult C57BL/6 mice (n=12) by administration of MNNG (5mg/kg, 0.1ml/intrarectal instillation) 2 times a week, for 2 week. Control group (n=12) received saline (0.1ml/intrarectal instillation). Eight weeks after beginning of MNNG administration animals were submitted to the forced swim test (FST) and the sucrose preference test for evaluation, respectively, of depressive- and anhedonia-like behaviors. After behavioral evaluation, the colon was collected and brain regions dissected (cortex-C, striatum-ST and hippocampus-HIP) for posterior evaluation of cytokine levels (IL-1β, IL-10, IL-17, and CX3CL1) by ELISA. Results: MNNG induced depressive-like behavior, represented by increased immobility time in the FST (Student t test, p < 0.05) and lower sucrose preference (Student t test, p < 0.05). Moreover, there were increased levels of IL-1β, IL-17 and CX3CL1 in the colonic tissue (Student t test, p < 0.05) and in the brain (IL-1 β in the ST and HIP, Student t test, p < 0.05; IL-17 and CX3CL1 in the C and HIP, p < 0.05). IL-10 levels, in contrast, were decreased in both the colon (p < 0.05) and the brain (C and HIP, p < 0.05). Conclusions: The results obtained in the present work support the notion that tumor growth induces neuroinflammation in stress-related brain regions and depressive-like behavior, which could be related to the high incidence of depression in colorectal carcinogenesis. This work have important clinical and research implications, taken into account that cytokine levels may be a marker promissory for the developing depression in CRC patients. New therapeutic strategies to assist in alleviating mental suffering in cancer patients might result from a better understanding of the role of cytokines in the pathophysiology of depression in these subjects.

Keywords: cytokines, brain, depression, colorectal cancer

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Authors: Ali Ashtiani, Cesar Carrasco

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Accurate determination of thermo-mechanical responses of jointed concrete pavement slabs is essential to implement an effective mechanistic design. Temperature-induced curling of concrete slabs can produce premature top-down cracking in rigid pavements. Curling of concrete slabs can result from daily temperature variation through the slab thickness. The slab curling can also result from temperature gradients due hot weather construction, drying shrinkage and creep that are permanently built into the slabs. The existence of permanent curling implies that concrete slabs are not flat at zero temperature gradient. In this case, slabs may not be in full contact with the underlying base layer when subjecting to traffic. Built-in curling can be a major factor producing loss of slab support. The magnitude of stresses induced in slabs is influenced by the stiffness of the underlying foundation layers and the contact condition along the slab-foundation interface. An approach for finite element modeling of the effect of loss of slab support due to built-in curling is presented in this paper. A series of parametric studies is carried out for a pavement system loaded with a combination of traffic and thermal loads, considering different built-in curling and different foundation rigidities. The results explain the effect of loss of support in the magnitude of stresses produced in concrete slabs. The results of parametric study can also be used to evaluate whether the governing equations that are used to idealize the behavior of jointed concrete pavements and the effect of loss of support have been accurately selected and implemented in the finite element model.

Keywords: built-in curling, finite element modeling, loss of slab support, rigid pavement

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Authors: Haile Nega Mulata, Seifu Daniel, Umeta Melaku, Wendwesson Ergete, Natesan Gnanasekaran

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Background: In Ethiopia, medicinal plants have been used for various human and animal diseases. In this study, we have examined the potential effect of hydroethanolic extract of Calpurnia aurea seed against hepatotoxicity and haematotoxicity induced by Highly Active Antiretroviral Therapy (HAART) drugs in Albino Wistar rats. Methods: We collected Matured dried seeds of Calpurnia aurea from northern Ethiopia (south Tigray and south Gondar) in June 2013. The powder of the dried seed sample was macerated with 70% ethanol and dried using rotavapor. We have investigated the Preliminary phytochemical tests and in-vitro antioxidant properties. Then, we induced toxicity with HAART drugs and gave the experimental animals different doses of the crude extract orally for thirty-five days. On the 35th day, the animals were fasted overnight and sacrificed by cervical dislocation. We collected the blood samples by cardiac puncture. We excised the liver and brain tissues for further histopathological studies. Subsequently, we analysed serum levels of the liver enzymes- Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Total Bilirubin, and Serum Albumin, using commercial kits in Cobas Integra 400 Plus Roche Analyzer Germany. We have also assessed the haematological profile using an automated haematology Analyser (Sysmex KX-2IN). Results: A significant (P<0.05) decrease in serum enzymes (ALT and AST) and total bilirubin were observed in groups that received the highest dose (300mg/kg) of the seed extract. And significant (P<0.05) elevation of total red blood cell count, haemoglobin, and hematocrit percentage was observed in the groups that received the seed extract compared to the HAART-treated groups. The WBC count mean values showed a statistically significant increase (p<0.05) in groups that received HAART and 200 and 300mg/kg extract, respectively. The histopathological observations also showed that the oral administration of varying doses of the crude extract of the seed reversed to a normal state. Conclusion: The hydroethanolic extract of the Calpurnia aurea seed lowered the hepatotoxicity and haematotoxicity in a dose-dependent manner. The antioxidant properties of the Calpurnia aurea seed extract may have possible protective effects against the drug's toxicity.

Keywords: calpurnia aurea, hepatotoxicity, haematotoxicity, antioxidant, histopathology, HAART

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Authors: Sanjeev K. Singh, Maloy B. Mandal, Revand R.

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The physiology of baroreceptors and chemoreceptors present in large blood vessels of the heart is well known in regulation of cardiorespiratory functions. Since large blood vessels and peripheral blood vessels are of same mesodermal origin, therefore, involvement of the latter in regulation of cardiorespiratory system is expected. Role of perivascular nerves in mediating cardiorespiratory alterations produced after intra-arterial injection of a nociceptive agent (bradykinin) was examined in urethane anesthetized male rats. Respiratory frequency, blood pressure, and heart rate were recorded for 30 min after the retrograde injection of bradykinin/saline in the femoral artery. In addition, paw edema was determined and water content was expressed as percentage of wet weight. Injection of bradykinin produced immediate tachypnoeic, hypotensive and bradycardiac responses of shorter latency (5-8 s) favoring the neural mechanisms involved in it. Injection of equi-volume of saline did not produce any responses and served as time matched control. Paw edema was observed in the ipsilateral hind limb. Pretreatment with diclofenac sodium significantly attenuated the bradykinin-induced responses and also blocked the paw edema. Ipsilateral femoral and sciatic nerve sectioning attenuated bradykinin-induced responses significantly indicating the origin of responses from the local vascular bed. Administration of bradykinin in the segment of an artery produced reflex cardiorespiratory changes by stimulating the perivascular nociceptors involving prostaglandins. This is a novel study exhibiting the role of peripheral blood vessels in regulation of cardiorespiratory system.

Keywords: vasosensory reflex, cardiorespiratory changes, nociceptive agent, bradykinin, VR1 receptors

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Authors: Angeliki Vassila, Dimitrios Kalogeropoulos, Rania Rawashdeh, Nigel Hall, Najiha Rahman, Mark Fabian, Suresh Thulasidharan, Hossain Parwez

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Introduction: Necrotising scleritis is a severe form of scleritis and poses a significant threat to vision. It can manifest in various systemic autoimmune disorders, systemic vasculitis, or as a consequence of microbial infections. The objective of this study is to present a case of necrotizing scleritis associated with scleroderma, which was further complicated by a secondary Staphylococcus epidermidis infection. Methods: This is a retrospective analysis that examines the medical records of a patient who was hospitalised in the Eye Unit at University Hospital Southampton. Results: A 78-year-old woman presented at the eye casualty department of our unit with a two-week history of progressively worsening pain in her left eye. She received a diagnosis of necrotising scleritis and was admitted to the hospital for further treatment. It was decided to commence a three-day course of intravenous methylprednisolone followed by a tapering regimen of oral steroids. Additionally, a conjunctival swab was taken, and two days later, it revealed the presence of S. epidermidis, indicating a potential secondary infection. Given this finding, she was also prescribed topical (Ofloxacin 0.3% - four times daily) and oral (Ciprofloxacin 750mg – twice daily) antibiotics. The inflammation and symptoms gradually improved, leading to the patient being scheduled for a scleral graft and applying an amniotic membrane to cover the area of scleral thinning. Conclusions: Rheumatoid arthritis and granulomatosis with polyangiitis are the most commonly identifiable systemic diseases associated with necrotising scleritis. Although association with scleroderma is extremely rare, early identification and treatment are necessary to prevent scleritis-related complications.

Keywords: scleritis, necrotizing scleritis, scleroderma, autoimmune disease

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