Search results for: cellular leakage

Authors: Priyanka Sharma, Niti Puri

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Anemia develops when blood lacks enough healthy erythrocytes. Past studies indicated that anemia, inflammatory process, and oxidative stress are interconnected. Erythrocytes are continuously exposed to reactive oxygen species (ROS) during circulation, due to normal aerobic cellular metabolism and also pathology of inflammatory diseases. Systemic mastocytosis and genetic depletion of mast cells have been shown to affect anaemia. In the present study, we attempted to reveal whether mast cells have a direct role in clearance or erythrophagocytosis of normal or oxidatively damaged erythrocytes. Murine erythrocytes were treated with tert-butyl hydroperoxidase (t-BHP), an agent that induces oxidative damage and mimics in vivo oxidative stress. Normal and oxidatively damaged erythrocytes were labeled with carboxyfluorescein succinimidyl ester (CFSE) to track erythrophagocytosis. We show, for the first time, direct erythrophagocytosis of oxidatively damaged erythrocytes in vitro by RBL-2H3 mast cells as well as in vivo by murine peritoneal mast cells. Also, activated mast cells, as may be present in inflammatory conditions, showed a significant increase in the uptake of oxidatively damaged erythrocytes than resting mast cells. This suggests the involvement of mast cells in erythrocyte clearance during oxidative stress or inflammatory disorders. Partial inhibition of phagocytosis by various inhibitors indicated that this process may be controlled by several pathways. Hence, our study provides important evidence for involvement of mast cells in severe anemia due to inflammation and oxidative stress and might be helpful to circumvent the adverse anemic disorders.

Keywords: mast cells, anemia, erythrophagocytosis, oxidatively damaged erythrocytes

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Authors: Hu-Jiang Shi, Li-Juan Zhu

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The implication of 5-hydroxytryptamine 2C receptor (5-HT2CR) in affective behaviors is a topic of debate, and the underlying mechanisms remain largely unclear. Here, we elucidate that the interaction between hippocampal neuronal nitric oxide synthase (nNOS) and carboxy-terminal PDZ ligand of nNOS (CAPON) contributes to the disruption of hippocampal excitation-inhibition (E/I) balance, which is responsible for the anxiety- and depressive-like behaviors caused by chronic stress-related 5-HT2CR signaling deficiency. In detail, activation or inhibition of 5-HT2CR by CP809101 or SB242084 modulates nNOS-CAPON interaction by influencing intracellular Ca²⁺ release. Notably, the dissociation of nNOS-CAPON abolishes SB242084-induced anxiety- and depressive-like behaviors, as well as the reduction in extracellular signal-regulated kinase (ERK)/cAMP-response element binding protein (CREB)/synapsin signaling and SNARE complex assembly. Furthermore, nNOS-CAPON blockers restore the impairments caused by SB242084, including the reduction in SNARE assembly-mediated γ-aminobutyric acid (GABA) vesicle release and a consequent shift of the E/I balance toward excitation in CA3 pyramidal neurons. Conclusively, our findings disclose the regulatory role of 5-HT2CR in anxiety- and depressive-like behaviors and highlight the hippocampal nNOS-CAPON coupling-triggered E/I imbalance as a pivotal cellular event underpinning the behavioral consequences of 5-HT2CR inhibition.

Keywords: 5-HT2CR, anxiety, depression, nNOS-CAPON coupling, excitation-inhibition balance, neurotransmitter release

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Authors: Sarita Puri, Tapan K. Chaudhuri

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Chaperonin GroEL is a tetradecameric Escherichia coli protein having identical subunits of 57 kDa. The elucidation of thermodynamic parameters related to stability for the native GroEL is not feasible as it undergoes irreversible unfolding because of its large size (800kDa) and multimeric nature. Nevertheless, it is important to determine the thermodynamic stability parameters for the highly stable GroEL protein as it helps in folding and holding of many substrate proteins during many cellular stresses. Properly folded monomers work as building-block for the formation of native tetradecameric GroEL. Spontaneous refolding behavior of monomeric GroEL makes it suitable for protein-denaturant interactions and thermodynamic stability based studies. The urea mediated unfolding is a three state process which means there is the formation of one intermediate state along with native and unfolded states. The heat mediated denaturation is a two-state process. The unfolding process is reversible as observed by the spontaneous refolding of denatured protein in both urea and head mediated refolding processes. Analysis of folding/unfolding data provides a measure of various thermodynamic stability parameters for the monomeric GroEL. The proposed mechanism of unfolding of monomeric GroEL is a three state process which involves formation of one stable intermediate having folded apical domain and unfolded equatorial, intermediate domains. Research in progress is to demonstrate the importance of specific residues in stability and oligomerization of GroEL protein. Several mutant versions of GroEL are under investigation to resolve the above mentioned issue.

Keywords: equilibrium unfolding, monomeric GroEl, spontaneous refolding, thermodynamic stability

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Authors: Nicola Menga, Giuseppe Carbone

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Although contact mechanics has been widely focused on the study of contacts between half-space, it has been recently pointed out that in presence of finite thickness elastic layers the results of the contact problem show significant difference in terms of the main contact quantities (e.g. contact area, penetration, mean pressure, etc.). Actually, there exist a wide range of industrial application demanding for this kind of studies, such as seals leakage prediction or pressure-sensitive coatings for electrical applications. In this work, we focus on the contact between a rigid profile and an elastic layer of thickness h confined under two different configurations: rigid constrain and applied uniform pressure. The elastic problem at hand has been formalized following Green’s function method and then numerically solved by means of a matrix inversion. We study different contact conditions, both considering and neglecting adhesive interactions at the interface. This leads to different solution techniques: Adhesive contacts equilibrium solution is found, in term of contact area for given penetration, making stationary the total free energy of the system; whereas, adhesiveless contacts are addressed defining an equilibrium criterion, again on the contact area, relying on the fracture mechanics stress intensity factor KI. In particular, we make the KI vanish at the edges of the contact area, as peculiar for adhesiveless elastic contacts. The results are obtained in terms of contact area, penetration, and mean pressure for both adhesive and adhesiveless contact conditions. As expected, in the case of a uniform applied pressure the slab turns out much more compliant than the rigidly constrained one. Indeed, we have observed that the peak value of the contact pressure, for both the adhesive and adhesiveless condition, is much higher for the rigidly constrained configuration than in the case of applied uniform pressure. Furthermore, we observed that, for little contact area, both systems behave the same and the pull-off occurs at approximately the same contact area and mean contact pressure. This is an expected result since in this condition the ratio between the layers thickness and the contact area is very high and both layer configurations recover the half-space behavior where the pull-off occurrence is mainly controlled by the adhesive interactions, which are kept constant among the cases.

Keywords: contact mechanics, adhesion, friction, thick layer

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Authors: Miesam Golzadeh Gangraj, Younes Parvasi, Mohammad Ghasemi, Ahmad Abdi, Saeid Fazelifar

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The purpose of the study was to determine the effect of glucose feeding on energy and hormonal indexes in plasma and lymphocyte immediately after wrestling – base techniques circuit exercise (WBTCE) in young male freestyle wrestlers. Sixteen wrestlers (weight = 75/45 ± 12/92 kg, age = 22/29 ± 0/90 years, BMI = 26/23 ± 2/64 kg/m²) were randomly divided into two groups: control (water), glucose (2 gr per kg body weight). Blood samples were obtained before, immediately, and 90 minutes of the post-exercise recovery period. Glucose (2 g/kg of body weight, 1W/5V) and water (equal volumes) solutions were given immediately after the second blood sampling. Data were analyzed by using an ANOVA (a repeated measure) and a suitable post hoc test (LSD). A significant decrease was observed in lymphocytes glycogen immediately after exercise (P < 0.001). In the experimental group, increase Lymphocyte glycogen concentration (P < 0.028) than in the control group in 90 min post-exercise. Plasma glucose concentrations increased in all groups immediately after exercise (P < 0.05). Plasma insulin concentrations in both groups decreased immediately after exercise, but at 90 min after exercise, its level was significantly increased only in glucose group (P < 0.001). Our results suggested that WBTCE protocol could be affected cellular energy sources and hormonal response. Furthermore, Glucose consumption can increase the lymphocyte glycogen and better energy within the cell.

Keywords: glucose feeding, lymphocyte, Wrestling – base techniques circuit , exercise

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Authors: Bahram Khan, Anderson Rocha Ramos, Rui R. Paulo, Fernando J. Velez

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With the growing demand for a new blend of applications, the users dependency on the internet is increasing day by day. Mobile internet users are giving more attention to their own experiences, especially in terms of communication reliability, high data rates and service stability on move. This increase in the demand is causing saturation of existing radio frequency bands. To address these challenges, researchers are investigating the best approaches, Carrier Aggregation (CA) is one of the newest innovations, which seems to fulfill the demands of the future spectrum, also CA is one the most important feature for Long Term Evolution - Advanced (LTE-Advanced). For this purpose to get the upcoming International Mobile Telecommunication Advanced (IMT-Advanced) mobile requirements (1 Gb/s peak data rate), the CA scheme is presented by 3GPP, which would sustain a high data rate using widespread frequency bandwidth up to 100 MHz. Technical issues such as aggregation structure, its implementations, deployment scenarios, control signal techniques, and challenges for CA technique in LTE-Advanced, with consideration of backward compatibility, are highlighted in this paper. Also, performance evaluation in macro-cellular scenarios through a simulation approach is presented, which shows the benefits of applying CA, low-complexity multi-band schedulers in service quality, system capacity enhancement and concluded that enhanced multi-band scheduler is less complex than the general multi-band scheduler, which performs better for a cell radius longer than 1800 m (and a PLR threshold of 2%).

Keywords: component carrier, carrier aggregation, LTE-advanced, scheduling

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Authors: Jimmy Jiun-Ming Su, Yuan-Min Lin

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Bioprinting has been applied to produce 3D cellular constructs for tissue engineering. Microextrusion printing is the most common used method. However, printing low viscosity bioink is a challenge for this method. Herein, we developed a new 3D printing system to fabricate cell-laden hydrogels via a DLP-based projector. The bioprinter is assembled from affordable equipment including a stepper motor, screw, LED-based DLP projector, open source computer hardware and software. The system can use low viscosity and photo-polymerized bioink to fabricate 3D tissue mimics in a layer-by-layer manner. In this study, we used gelatin methylacrylate (GelMA) as bioink for stem cell encapsulation. In order to reinforce the printed construct, surface modified hydroxyapatite has been added in the bioink. We demonstrated the silanization of hydroxyapatite could improve the crosslinking between the interface of hydroxyapatite and GelMA. The results showed that the incorporation of silanized hydroxyapatite into the bioink had an enhancing effect on the mechanical properties of printed hydrogel, in addition, the hydrogel had low cytotoxicity and promoted the differentiation of embedded human bone marrow stem cells (hBMSCs) and retinal pigment epithelium (RPE) cells. Moreover, this bioprinting system has the ability to generate microchannels inside the engineered tissues to facilitate diffusion of nutrients. We believe this 3D bioprinting system has potential to fabricate various tissues for clinical applications and regenerative medicine in the future.

Keywords: bioprinting, cell encapsulation, digital light processing, GelMA hydrogel

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Authors: Yaara Oppenheimer-Shaanan, Nimrod Nachmias, Marina Campos Rocha, Neta Schlezinger, Noam Dotan, Asaf Levy

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Fusarium oxysporum, a fungus that attacks a broad range of plants and can cause infections in humans, operates across different kingdoms. This pathogen encounters varied conditions, such as temperature, pH, and nutrient availability, in plant and human hosts. The Fusarium oxysporum species complex, pervasive in soils globally, can affect numerous plants, including key crops like tomatoes and bananas. Controlling Fusarium infections can involve biocontrol agents that hinder the growth of harmful strains. Our research developed a computational method to identify toxin domains within a vast number of microbial genomes, leading to the discovery of nine distinct toxins capable of killing bacteria and fungi, including Fusarium. These toxins appear to function as enzymes, causing significant damage to cellular structures, membranes and DNA. We explored biological control using bacteria that produce polymorphic toxins, finding that certain bacteria, non-pathogenic to plants, offer a safe biological alternative for Fusarium management, as they did not harm macrophage cells or C. elegans. Additionally, we elucidated the 3D structures of two toxins with their protective immunity proteins, revealing their function as unique DNases. These potent toxins are likely instrumental in microbial competition within plant ecosystems and could serve as biocontrol agents to mitigate Fusarium wilt and related diseases.

Keywords: microbial toxins, antifungal, Fusarium oxysporum, bacterial-fungal intreactions

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Authors: Djamel Fawzi Hadj Sadok, Marrone Silvério Melo Dantas Pedro Henrique Dreyer, Gabriel Fonseca Reis de Souza, Daniel Bezerra, Ricardo Souza, Silvia Lins, Judith Kelner

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A radio base station (RBS), part of the radio access network, is a particular type of equipment that supports the connection between a wide range of cellular user devices and an operator network access infrastructure. Nowadays, most of the RBS maintenance is carried out manually, resulting in a time consuming and costly task. A suitable candidate for RBS maintenance automation is repairing faulty links between devices caused by missing or unplugged connectors. A suitable candidate for RBS maintenance automation is repairing faulty links between devices caused by missing or unplugged connectors. This paper proposes and compares two deep learning solutions to identify attached RJ45 connectors on network ports. We named connector detection, the solution based on object detection, and connector classification, the one based on object classification. With the connector detection, we get an accuracy of 0:934, mean average precision 0:903. Connector classification, get a maximum accuracy of 0:981 and an AUC of 0:989. Although connector detection was outperformed in this study, this should not be viewed as an overall result as connector detection is more flexible for scenarios where there is no precise information about the environment and the possible devices. At the same time, the connector classification requires that information to be well-defined.

Keywords: radio base station, maintenance, classification, detection, deep learning, automation

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Authors: Grace O. Akinlade, Danjuma D. Maza, Oluwakemi O. Olawolu, Delight O. Babalola, John A. O. Oyekunle, Joshua O. Ojo

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The Mokuro area of Ile-Ife, South West Nigeria, was well known for gold mining in the past (about twenty years ago). However, the place has since been reclaimed and converted to residential area without any environmental risk assessment of the impact of the mining tailings on the environment. Soil, water, and plant samples were collected from 4 different locations around the mine-turned-residential area. Soil samples were pulverized and sieved into finer particles, while the plant samples were dried and pulverized. All the samples were digested and analyzed for As, Pb, Cd, and Zn using atomic absorption spectroscopy (AAS). From the analysis results, the hazard index (HI) was then calculated for the metals. The soil and plant samples were air dried and pulverized, then weighed, after which the samples were packed into special and properly sealed containers to prevent radon gas leakage. After the sealing, the samples were kept for 28 days to attain secular equilibrium. The concentrations of 40K, 238U, and 232Th in the samples were measured using a cesium iodide (CsI) spectrometer and URSA software. The AAS analysis showed that As, Pb, Cd (Toxic metals), and Zn (essential trace metals) are in concentrations lower than permissible limits in plants and soil samples, while the water samples had concentrations higher than permissible limits. The calculated health indices (HI) show that HI for water is >1 and that of plants and soil is <1. Gamma spectrometry result shows high levels of activity concentrations above the recommended limits for all the soil and plant samples collected from the area. Only the water samples have activity concentrations below the recommended limit. Consequently, the absorbed dose, annual effective dose, and excess lifetime cancer risk are all above the recommended safe limit for all the samples except for water samples. In conclusion, all the samples collected from the area are either contaminated with toxic metals or they pose radiological hazards to the consumers. Further detailed study is therefore recommended in order to be able to advise the residents appropriately.

Keywords: toxic metals, gamma spectrometry, Ile-Ife, radiological hazards, gold mining

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Authors: Chieh-Chung Tsou, Chun-Min Lo, Yeh-Shiu Chu

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Cell’s mechanical forces provide important physical cues in regulation of proper cellular functions, such as cell differentiation, proliferation and migration. It is believed that adhesive forces generated by cell-cell interaction are able to transmit to the interior of cell through filamentous cortical cytoskeleton. Prominent among other membrane receptors, Cadherins are prototypical adhesive molecules able to generate remarkable forces to regulate intercellular adhesion. However, the mechanistic steps of mechano-transduction in Cadherin-mediated adhesion remain very controversial. We are interested in understanding how Cadherin protein complexes enable force generation and transmission at cell-cell contact in the initial stage of intercellular adhesion. For providing a better control of time, space, and substrate stiffness, in this study, a combination of protein micropattern, micropipette manipulation, and traction force microscopy is used. Pair micropattern with different forms confines cell spreading area and the gaps in pairs varied from 2 to 8 microns are applied for monitoring the forces that cell pairs generated, measured by traction force microscopy. Moreover, cell clones obtained from epithelial cells undergone genome editing are used to score the importance for known components of Cadherin complexes in force generation. We believe that our results from this combinatory mechanobiological method will provide deep insights on understanding the biophysical principle governing mechano- transduction of Cadherin-mediated intercellular adhesion.

Keywords: cadherin, intercellular adhesion, protein micropattern, traction force microscopy

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Authors: Elham Mansouri, Asghar Mesbahi

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Purpose: In the current study, we aimed to investigate the macroscopic and microscopic dose enhancement effect of metallic nanoparticles in interstitial brachytherapy of uterus cancer by Iodin-125 source using a nano-lattice model in MCNPX (5) and MCNP6.1 codes. Materials and methods: Based on a nano-lattice simulation model containing a radiation source and a tumor tissue with cellular compartments loaded with 7mg/g spherical nanoparticles (bismuth, gold, and gadolinium), the energy deposited by the secondary electrons in microscopic and macroscopic level was estimated. Results: The results show that the values of macroscopic DEF is higher than microscopic DEF values and the macroscopic DEF values decreases as a function of distance from the brachytherapy source surface. Also, the results revealed a remarkable discrepancy between the DEF and secondary electron spectra calculated by MCNPX (5) and MCNP6.1 codes, which could be justified by the difference in energy cut-off and electron transport algorithms of two codes. Conclusion: According to the both MCNPX (5) and MCNP6.1 outputs, it could be concluded that the presence of metallic nanoparticles in the tumor tissue of uteruscancer increases the physical effectiveness of brachytherapy by I-125 source. The results presented herein give a physical view of radiosensitization potential of different metallic nanoparticles and could be considered in design of analytical and experimental radiosensitization studies in tumor regions using various radiotherapy modalities in the presence of heavy nanomaterials.

Keywords: MCNPX, MCNP6, nanoparticle, brachytherapy

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Authors: Christian Neunzig, Simon Fahle, Jürgen Schulz, Matthias Möller, Bernd Kuhlenkötter

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Manufacturing companies are facing global competition and enormous cost pressure. The use of machine learning applications can help reduce production costs and create added value. Predictive quality enables the securing of product quality through data-supported predictions using machine learning models as a basis for decisions on test results. Furthermore, machine learning methods are able to process large amounts of data, deal with unfavourable row-column ratios and detect dependencies between the covariates and the given target as well as assess the multidimensional influence of all input variables on the target. Real production data are often subject to highly fluctuating boundary conditions and unbalanced data sets. Changes in production data manifest themselves in trends, systematic shifts, and seasonal effects. Thus, Machine learning applications require intensive pre-processing and feature selection. Data preprocessing includes rule-based data cleaning, the application of dimensionality reduction techniques, and the identification of comparable data subsets. Within the used real data set of Bosch hydraulic valves, the comparability of the same production conditions in the production of hydraulic valves within certain time periods can be identified by applying the concept drift method. Furthermore, a classification model is developed to evaluate the feature importance in different subsets within the identified time periods. By selecting comparable and stable features, the number of features used can be significantly reduced without a strong decrease in predictive power. The use of cross-process production data along the value chain of hydraulic valves is a promising approach to predict the quality characteristics of workpieces. In this research, the ada boosting classifier is used to predict the leakage of hydraulic valves based on geometric gauge blocks from machining, mating data from the assembly, and hydraulic measurement data from end-of-line testing. In addition, the most suitable methods are selected and accurate quality predictions are achieved.

Keywords: classification, achine learning, predictive quality, feature selection

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Authors: Shima Dehghan

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Aim: imbalance between antioxidant defensive system and increasing production of free radicals caused oxidative stress that can be rolled in cellular damage and occurring some of diseases such as diabetes. The aim of current study was to investigate the effect of eight weeks aerobic training on peroxidant and antioxidants indicators in women with type2 diabetes. Methodology: thirty two inactive women with type 2 diabetes were randomly assigned into four groups: 1. control, 2. Aerobic training, 3. Purslane seed and 4. Aerobic training + Purslane seed groups. Subjects were asked to accomplish eight weeks aerobic training (50 min aerobic exercise, 3 days/week, for to achieve 65-75% maximum of heart rate). Also, subjects in certain groups received purslane seeds for eight weeks. Blood samples were obtained in two sets (one session and after 8 weeks). Data was analyzed using one way ANOVA. A significant difference was accepted at p < 0/05 level. Results: After eight weeks of aerobic training with purslane seeds supplementation, malon dyaldehyde (MDA) concentration in training group were significantly decreased (p < 0/000), but A difference significant was not found in control group. Superoxide dismutase (SOD) and catalase (CAT) concentrations in training group were significantly increased (p < 0/000), while difference significant wasnot found in control group. Conclusion: The finding of the current study indicates that disciplined aerobic training with purslane seeds supplementation can be caused improvement in peroxidant/antioxidant balance in women with type2 diabetes.

Keywords: aerobic training, purslane seed, peroxidant/antioxidant balance, diabetes2

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Authors: Ava Faridi, Pouya Faridi, Aleksandr Kakinen, Ibrahim Javed, Thomas P. Davis, Pu Chun Ke

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Human islet amyloid polypeptide (IAPP) is a hormone associated with glycemic control and type 2 diabetes. Biophysically, the chirality of IAPP fibrils has been little explored with respect to the aggregation and toxicity of the peptide. Biochemically, it remains unclear as for how protein expression in pancreatic beta cells may be altered by cell exposure to the peptide, and how such changes may be mitigated by nanoparticle inhibitors for IAPP aggregation. In this study, we first demonstrated the elimination of the IAPP nucleation phase and shortening of its elongation phase by silica nanoribbons. This accelerated IAPP fibrillization translated to reduced toxicity, especially for the right-handed silica nanoribbons, as revealed by cell viability, helium ion microscopy, as well as zebrafish embryo survival, developmental and behavioral assays. We then examined the proteomes of βTC6 pancreatic beta cells exposed to the three main aggregation states of monomeric, oligomeric and amyloid fibrillar IAPP, and compared that with cellular protein expression modulated by graphene quantum dots (GQDs). A total of 29 proteins were significantly regulated by different forms of IAPP, and the majority of these proteins were nucleotide-binding proteins. A regulatory capacity of GQDs against aberrant protein expression was confirmed. These studies have demonstrated the great potential of employing nanomaterials targeting the mesoscopic enantioselectivity and protein expression dysregulation in pancreatic beta cells.

Keywords: graphene quantum dots, IAPP, silica nanoribbons, protein expression, toxicity

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Authors: Nashwa A. Mohamed

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Introduction: Omeprazole is a proton pump inhibitor used commonly in the treatment of acid-peptic disorders. Although omeprazole is generally well tolerated, serious adverse effects such as renal failure have been reported. Ginger is an antioxidant that could play a protective role in models of experimentally induced nephropathies. Aim of the work: The aim of this work was to study the possible histological changes induced by omeprazole on renal cortex and evaluate the possible protective effect of ginger on omeprazole-induced renal damage in adult male albino rats. Materials and methods: Twenty-four adult male albino rats divided into four groups (six rats each) were used in this study. Group I served as the control group. Rats of group II received only an aqueous extract of ginger daily for 3 months through a gastric tube. Rats of group III were received omeprazole orally through a gastric tube for 3 months. Rats of group IV were given both ginger and omeprazole at the same doses and through the same routes as the previous two groups. At the end of the experiment, the rats were sacrificed. Renal tissue samples were processed for light, immunohistochemical and electron microscopic examination. The obtained results were analysed morphometrically and statistically. Results: Omeprazole caused several histological changes in the form of loss of normal appearance of renal cortex with degenerative changes in the renal corpuscle and tubules. Cellular infilteration was also observed. The filteration barrier was markedly affected. Ginger ameliorated the omeprazole-induced histological changes. Conclusion: Omeprazole induced injurious effects on renal cortex. Coadministration of ginger can ameliorate the histological changes induced by omeprazole.

Keywords: ginger, kidney, omeprazole, rat

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Authors: Olusola Olalekan Elekofehinti, Isaac Gbadura Adanlawo, Joao Batista Teixeira Rocha

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We evaluated the potential neuroprotective effect of Phyllantus nuriri against Fe2+ and SNP induced oxidative stress in mitochondria of rats brain. Cellular viability was assessed by MTT reduction, reactive oxygen species (ROS) generation was measured using the probe 2,7-dichlorofluorescein diacetate (DCFH-DA). Glutathione content was measured using dithionitrobenzoic acid (DTNB). Fe2+ (10µM) and SNP (5µM) significantly decreased mitochondrial activity, assessed by MTT reduction assay, in a dose-dependent manner, this occurred in parallel with increased glutathione oxidation, ROS production and lipid peroxidation end-products (thiobarbituric acid reactive substances, TBARS). The co-incubation with methanolic extract of Phyllantus nuriri (10-100 µg/ml) reduced the disruption of mitochondrial activity, gluthathione oxidation, ROS production as well as the increase in TBARS levels caused by both Fe2+ and SNP in a dose dependent manner. HPLC analysis of the extract revealed the presence of gallic acid (20.54±0.01), caffeic acid (7.93±0.02), rutin (25.31±0.05), quercetin (31.28±0.03) and kaemferol (14.36±0.01). This result suggests that these phytochemicals account for the protective actions of Phyllantus nuriri against Fe2+ and SNP -induced oxidative stress. Our results show that Phyllantus nuriri consist important bioactive molecules in the search for an improved therapy against the deleterious effects of Fe2+, an intrinsic producer of reactive oxygen species (ROS), that leads to neuronal oxidative stress and neurodegeneration.

Keywords: Phyllantus niruri, neuroprotection, oxidative stress, mitochondria, synaptosome

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Authors: Kambiz Rasoulkhani, Jeanne Cole, Sybil Sharvelle, Ali Mostafavi

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Dual water distribution systems have been proposed as solutions to enhance the sustainability and resilience of urban water systems by improving performance and decreasing energy consumption. The objective of this study was to evaluate the long-term resilience and robustness of dual water distribution systems versus singular water distribution systems under various stressors such as demand fluctuation, aging infrastructure, and funding constraints. To this end, the long-term dynamics of these infrastructure systems was captured using a simulation model that integrates institutional agency decision-making processes with physical infrastructure degradation to evaluate the long-term transformation of water infrastructure. A set of model parameters that varies for dual and singular distribution infrastructure based on the system attributes, such as pipes length and material, energy intensity, water demand, water price, average pressure and flow rate, as well as operational expenditures, were considered and input in the simulation model. Accordingly, the model was used to simulate various scenarios of demand changes, funding levels, water price growth, and renewal strategies. The long-term resilience and robustness of each distribution infrastructure were evaluated based on various performance measures including network average condition, break frequency, network leakage, and energy use. An ecologically-based resilience approach was used to examine regime shifts and tipping points in the long-term performance of the systems under different stressors. Also, Classification and Regression Tree analysis was adopted to assess the robustness of each system under various scenarios. Using data from the City of Fort Collins, the long-term resilience and robustness of the dual and singular water distribution systems were evaluated over a 100-year analysis horizon for various scenarios. The results of the analysis enabled: (i) comparison between dual and singular water distribution systems in terms of long-term performance, resilience, and robustness; (ii) identification of renewal strategies and decision factors that enhance the long-term resiliency and robustness of dual and singular water distribution systems under different stressors.

Keywords: complex systems, dual water distribution systems, long-term resilience performance, multi-agent modeling, sustainable and resilient water systems

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Authors: Mateen A. Khan, Elizabeth J. Theil, Dixie J. Goss

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Cellular iron homeostasis is accomplished by the coordinated regulated expression of iron uptake, storage, and export. Iron regulate the translation of ferritin and mitochondrial aconitase iron responsive element (IRE)-mRNA by interaction with an iron regulatory protein (IRPs). Iron increases protein biosynthesis encoded in iron responsive element. The noncoding structure IRE-mRNA, approximately 30-nt, folds into a stem loop to control synthesis of proteins in iron trafficking, cell cycling, and nervous system function. Fluorescence anisotropy measurements showed the presence of one binding site on IRP1 for ferritin and mitochondrial aconitase IRE-mRNA. Scatchard analysis revealed the binding affinity (Kₐ) and average binding sites (n) for ferritin and mitochondrial aconitase IRE-mRNA were 68.7 x 10⁶ M⁻¹ and 9.2 x 10⁶ M⁻¹, respectively. In order to understand the relative importance of equilibrium and stability, we further report the contribution of electrostatic interactions in the overall binding of two IRE-mRNA with IRP1. The fluorescence quenching of IRP1 protein was measured at different ionic strengths. The binding affinity of IRE-mRNA to IRP1 decreases with increasing ionic strength, but the number of binding sites was independent of ionic strength. Such results indicate a differential contribution of electrostatics to the interaction of IRE-mRNA with IRP1, possibly related to helix bending or stem interactions and an overall conformational change. Selective destabilization of ferritin and mitochondrial aconitase RNA/protein complexes as reported here explain in part the quantitative differences in signal response to iron in vivo and indicate possible new regulatory interactions.

Keywords: IRE-mRNA, IRP1, binding, ionic strength

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Authors: Shima Mahmoudi, Babak Pourakbari, Setareh Mamishi, Mostafa Teymuri, Majid Marjani

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Although cytokine analysis has greatly contributed to the understanding of tuberculosis (TB) pathogenesis, data on cytokine profiles that might distinguish progression from latency of TB infection are scarce. Since PE/PPE proteins are known to induce strong humoral and cellular immune responses, the aim of this study was to evaluate the diagnostic potential of interleukin-2 (IL-2) as biomarker after specific antigen stimulation with PE35 and PPE68 for the discrimination of active and latent tuberculosis infection (LTBI). The production of IL-2 was measured in the antigen-stimulated whole-blood supernatants following stimulation with recombinant PE35 and PPE68. All the patients with active TB and LTBI had positive QuantiFERON-TB Gold in Tube test. The level of IL-2 following stimulation with recombinant PE35 and PPE68 were significantly higher in LTBI group than in patients with active TB infection or control group. The discrimination performance (assessed by the area under ROC curve) for IL-2 following stimulation with recombinant PE35 and PPE68 between LTBI and patients with active TB were 0.837 (95%CI: 0.72-0.97) and 0.75 (95%CI: 0.63-0.89), respectively. Applying the 12.4 pg/mL cut-off for IL-2 induced by PE35 in the present study population resulted in sensitivity of 78%, specificity of 78%, PPV of 78% and NPV of 100%. In addition, a sensitivity of 81%, specificity of 70%, PPV of 67% and 87% of NPV was reported based on the 4.4 pg/mL cut-off for IL-2 induced by PPE68. In conclusion, peptides of the antigen PE35 and PPE68, absent from commonly used BCG strains, stimulated strong IL-2- positive T cell responses in patients with LTBI. This study confirms IL-2 induced by PE35 and PPE68 as a sensitive and specific biomarker and highlights IL-2 as new promising adjunct markers for discriminating of LTBI and Active TB infection.

Keywords: IL-2, PE35, PPE68, tuberculosis

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Authors: Chiagoziem A. Otuechere, Ebenezer O. Farombi

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The protective effect of dichloromethane: methanol extract of Pterocarpus mildbraedii (PME), a widely consumed Nigerian leafy vegetable, on the toxicity of propanil was investigated in male rats. Animals were distributed into eight groups of five each. Group 1 served as control and received normal saline while rats in groups 2, 3, and 4 received 100 mg/kg, 200 mg/kg, and 400 mg/kg extract doses respectively. Group 5 rats were orally administered 200 mg/kg propanil while groups 6, 7, and 8 rats were given propanil plus extract. Oral administration of propanil elicited a 14.8%, 5%, 122%, and 78% increase in the activity of serum enzymes; alanine aminotransferase (AST), alanine aminotransferase(ALT), Alkaline phoshatase (ALP) and Gamma glutamyl transferase (ﻻGT). There were also increase in Lactate dehydrogenase (LDH) activity, direct bilirubin and lipid peroxidation levels. Furthermore, PME significantly attenuated the marked hepatic oxidative damage that accompanied propanil treatment. The extract significantly decreased LDH activity and bilirubin levels following propanil treatment. Furthermore, propanil-induced alterations in the activities of antioxidant enzymes: Superoxide dismutase (SOD), catalase (CAT) and glutathione s-transferase (GST) in these rats were modulated by the extract. The percentage DPPH Radical Scavenging Activity of the extract was determined as 55% and compared to those of Gallic acid (49%). Hepatic histology examination further confirmed the damage to the liver as it revealed severe periportal cellular infiltration of the hepatocytes. These biochemical and morphological alterations were attenuated in rats pre-treated with 100 mg/kg and 200 mg/kg doses of the extract. These results suggest that PME possesses protective effect against propanil-induced hepatotoxicity.

Keywords: antioxidant, hepatoprotection, Pterocarpus mildbraedii, propanil

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Authors: Nasrin Takzaree, Gholamreza Hassanzadeh, Abbas Hadjiakhoondi, Mohammadreza Rouini

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Introduction: Today herbal medicine are extensively used for various therapeutic reasons. Whereas Achillea millefolium L. comprises different chemical compounds it is used in classic and modern medicine for different purposes. Concerning the family planning as a principle matter, the idea of using specific herbal medicine is of great importance. Purpose: To investigate the effects of Achillea millefolium L. extract on fertility power and spermatogenesis process in male mature Wistar rats and the anti-fertility effects of this extract in male genital system. Material and methods: In this study 32 male mature Wistar rats were randomly divided in to 4 experimental groups. 1st experimental group included 8 rats receiving Achillea millefolium extract at the dose of 200 mg/kg intraperitoneally. Second and third groups received the extract the same at the doses of 400 and 800 mg/kg respectively. 4th group was considered as control group in which the parenteral distilled water was administered. after 20 days, rats were sacrificed and the spermatogenesis process was histologically examined. Results: In experimental groups receiving high doses of extract comparing with control group, thickness in seminiferous tubules basal membrane, decrease in germinal epithelium cells, congestion in testicular tissue, disarrangement in germinal epithelium cells as well as decrease in cellular condense were observed (p<0.001). Conclusion: Findings suggest that alcoholic extract of Achillea millefolium at high concentrations lead to the structural alterations and changes in spermatogenesis in testicular tissue.

Keywords: spermatogenesis, alcoholic extract of Achillea millefolium L., testis, Wistar rat

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Authors: Ahmed Abdulrahman, Jalal Foroozesh

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CO₂ based enhanced oil recovery (EOR) techniques have gained massive attention from major oil firms since they resolve the industry's two main concerns of CO₂ contribution to the greenhouse effect and the declined oil production. Carbonated water injection (CWI) is a promising EOR technique that promotes safe and economic CO₂ storage; moreover, it mitigates the pitfalls of CO₂ injection, which include low sweep efficiency, early CO₂ breakthrough, and the risk of CO₂ leakage in fractured formations. One of the main challenges that hinder the wide adoption of this EOR technique is the complexity of accurate modeling of the kinetics of CO₂ mass transfer. The mechanisms of CO₂ mass transfer during CWI include the slow and gradual cross-phase CO₂ diffusion from carbonated water (CW) to the oil phase and the CO₂ dispersion (within phase diffusion and mechanical mixing), which affects the oil physical properties and the spatial spreading of CO₂ inside the reservoir. A 2D non-equilibrium compositional simulator has been developed using a fully implicit finite difference approximation. The material balance term (k) was added to the governing equation to account for the slow cross-phase diffusion of CO₂ from CW to the oil within the gird cell. Also, longitudinal and transverse dispersion coefficients have been added to account for CO₂ spatial distribution inside the oil phase. The CO₂-oil diffusion coefficient was calculated using the Sigmund correlation, while a scale-dependent dispersivity was used to calculate CO₂ mechanical mixing. It was found that the CO₂-oil diffusion mechanism has a minor impact on oil recovery, but it tends to increase the amount of CO₂ stored inside the formation and slightly alters the residual oil properties. On the other hand, the mechanical mixing mechanism has a huge impact on CO₂ spatial spreading (accurate prediction of CO₂ production) and the noticeable change in oil physical properties tends to increase the recovery factor. A sensitivity analysis has been done to investigate the effect of formation heterogeneity (porosity, permeability) and injection rate, it was found that the formation heterogeneity tends to increase CO₂ dispersion coefficients, and a low injection rate should be implemented during CWI.

Keywords: CO₂ mass transfer, carbonated water injection, CO₂ dispersion, CO₂ diffusion, cross phase CO₂ diffusion, within phase CO2 diffusion, CO₂ mechanical mixing, non-equilibrium simulation

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Authors: Magdy Al Shourbagi

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Diabetes mellitus is the commonest cause of neuropathy. The common pattern is a distal symmetrical sensory polyneuropathy, associated with autonomic disturbances. Less often, Diabetes mellitus is responsible for a focal or multifocal neuropathy. Common causes for non-healing of diabetic foot are the infection and ischemia. Diabetes mellitus is associated with a defective cellular and humoral immunity. Particularly, decreased phagocytosis, decreased chemotaxis, impaired bacterial killing and abnormal lymphocytic function resulting in a reduced inflammatory reaction and defective wound healing. Hyperbaric oxygen therapy is defined by the Undersea and Hyperbaric Medical Society as a treatment in which a patient intermittently breathes 100% oxygen and the treatment chamber is pressurized to a pressure greater than sea level (1 atmosphere absolute). The pressure increase may be applied in mono-place (single person) or multi-place chambers. Multi-place chambers are pressurized with air, with oxygen given via face mask or endotracheal tube; while mono-place chambers are pressurized with oxygen. Oxygen gas plays an important role in the physiology of wound healing. Hyperbaric oxygen therapy can raise tissue oxygen tensions to levels where wound healing can be expected. HBOT increases the killing ability of leucocytes also it is lethal for certain anaerobic bacteria and inhibits toxin formation in many other anaerobes. Multiple anecdotal reports and studies in HBO therapy in diabetic patients report that HBO can be an effective adjunct therapy in the management of diabetic foot wounds and is associated with better functional outcomes.

Keywords: hyperbari oxygen therapy, diabetic foot, neuropathy, multiplace chambers

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Authors: Dhruv J. Limaye, Hanga Galfalvy, Cheick A. Sissoko, Yung-yu Huang, Chunanning Tang, Ying Liu, Shu-Chi Hsiung, Andrew J. Dwork, Gorazd B. Rosoklija, Victoria Arango, Lewis Brown, J. John Mann, Maura Boldrini

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Memory and emotion require hippocampal cell viability and connectivity and are disrupted in major depressive disorder (MDD). Applying shotgun proteomics and stereological quantification of neural progenitor cells (NPCs), intermediate neural progenitors (INPs), and mature granule neurons (GNs), to postmortem human hippocampus, identified differentially expressed proteins (DEPs), and fewer NPCs, INPs and GNs, in untreated MDD (uMDD) compared with non-psychiatric controls (CTRL) and antidepressant-treated MDD (MDDT). DEPs lower in uMDD vs. CTRL promote mitosis, differentiation, and prevent apoptosis. DEPs higher in uMDD vs. CTRL inhibit the cell cycle, and regulate cell adhesion, neurite outgrowth, and DNA repair. DEPs lower in MDDT vs. uMDD block cell proliferation. We observe group-specific correlations between numbers of NPCs, INPs, and GNs and an abundance of proteins regulating mitosis, differentiation, and apoptosis. Altered protein expression underlies hippocampus cellular and volume loss in uMDD, supports a trophic effect of antidepressants, and offers new treatment targets.

Keywords: proteomics, hippocampus, depression, mitosis, migration, differentiation, mitochondria, apoptosis, antidepressants, human brain

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Authors: JaeYoon Lee, Gi-Hoon Yang, JongHan Ha, MyungGu Yeo, SeungHyun Ahn, Hyeongjin Lee, HoJun Jeon, YongBok Kim, Minseong Kim, GeunHyung Kim

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One of the important factors in tissue engineering is to design optimal biomedical scaffolds, which can be governed by topographical surface characteristics, such as size, shape, and direction. Of these properties, we focused on the effects of nano- to micro-sized hierarchical surface. To fabricate the hierarchical surface structure on poly(ε-caprolactone) (PCL) film, we employed a micro-casting technique by pressing the mold and nano-etching technique using a modified plasma process. The micro-sized topography of PCL film was controlled by sizes of the micro structures on lotus leaf. Also, the nano-sized topography and hydrophilicity of PCL film were controlled by a modified plasma process. After the plasma treatment, the hydrophobic property of the PCL film was significantly changed into hydrophilic property, and the nano-sized structure was well developed. The surface properties of the modified PCL film were investigated in terms of initial cell morphology, attachment, and proliferation using osteoblast-like-cells (MG63). In particular, initial cell attachment, proliferation and osteogenic differentiation in the hierarchical structure were enhanced dramatically compared to those of the smooth surface. We believe that these results are because of a synergistic effect between the hierarchical structure and the reactive functional groups due to the plasma process. Based on the results presented here, we propose a new biomimetic surface model that maybe useful for effectively regenerating hard tissues.

Keywords: hierarchical surface, lotus leaf, nano-etching, plasma treatment

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Authors: Khosro Ghazvinian, Touba Khodaeian

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To improve the oxidative stability of meat products, the use of dietary form of antioxidants can extend the shelf life and acceptability of muscle food during exposition or storage condition. As shown, this method is more effective than adding direct preservatives due to uniform incorporation of dietary additives into sub cellular membrane and therefore, they can properly inhibit the oxidative reaction at their localized sites. Furthermore, postmortem addition of antioxidants to meat cannot directly inhibit the oxidation in membrane phospholipids. Therefore, this study was designed to evaluate the effects of feed supplementation with Melissa officinalis leaves on lipid peroxidation of chicken breast fillets during refrigerated storage. In this study, 72 one-day old Ross 308 broilers distributed in four groups with six replicates (3 chickens each) were fed a basal diet (CONT) or basal diet supplemented with 5, 10, and 15 gr/Kg M.officinalis, for 6 weeks. Following slaughter, fillets from breast were stored at 4 °C in the dark for 12 days, and lipid oxidation was assessed on the basis of thiobarbituric acid reactive substances (TBARS) formed. Results showed that incorporation of M.officinalis in broiler diets delayed lipid oxidation in raw breast meat during refrigerated storage comparative with CONT(p<0.05). In this regard, TBARS levels of breast samples containing higher concentrations (10 and 15 gr/Kg) of M. officinalis (625.43 and 504.32 µg/kg MDA equivalents, respectively )were significantly lower than those of control and 5g/kg samples (872.75 and 841.32 µg/kg MDA equivalents, respectively) (p<0.05). Therefore, M. officinalis might be utilized in novel applications as a nutritional supplement or a functional food component.

Keywords: breast fillet, lipid oxidation, Melissa officinalis, TBARS assay

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Authors: Nick Weir, Robert Stevens, Alan Hargreaves, Martin McGinnity, Chris Tinsley

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Hydrophobic materials have previously demonstrated the ability to elevate cell-cell interactions and promote the formation of neural networks whilst aligned nanofibers demonstrate the ability to induce extensive neurite outgrowth in an aligned manner. Hydrophobic materials typically elicit an immune response upon implantation and thus materials used for implantation are typically hydrophilic. Poly-L-lactic acid (PLLA) is a hydrophobic, non-immunogenic, FDA approved material that can be electrospun to form aligned nanofibers. Primary rat cortical neurons cultured for 10 days on aligned PLLA nanofibers formed 3D cell clusters, approximately 800 microns in diameter. Neurites that extended from these clusters were highly aligned due to the alignment of the nanofibers they were cultured upon and fasciculation was also evident. Plasma treatment of the PLLA nanofibers prior to seeding of cells significantly reduced the hydrophobicity and abolished the cluster formation and neurite fasciculation, whilst reducing the extent and directionality of neurite outgrowth; it is proposed that hydrophobicity induces the changes to cellular behaviors. Aligned PLLA nanofibers induced the formation of a structure that mimics the grey-white matter compartmentalization that is observed in vivo and thus represents a step forward in generating organoids or biomaterial-based implants. Upon implantation into the brain, the biomaterial architectures described here may provide a useful platform for both brain repair and brain remodeling initiatives.

Keywords: hydrophobicity, nanofibers, neurite fasciculation, neurite outgrowth, PLLA

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Authors: Gyati Shilakari Asthana, Abhay Asthana

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Purpose: The therapeutic potential of oligonucleotide (ODN) is primarily dependent upon its safe and efficient delivery to specific cells overcoming degradation and maximizing cellular uptake in vivo. The present study is focused to design low molecular weight chitosan nanoconstructs to meet the requirements of safe and effectual delivery of ODNs. LMW-chitosan is a biodegradable, water soluble, biocompatible polymer and is useful as a non-viral vector for gene delivery due to its better stability in water. Methods: LMW chitosan ODN nanoparticles (CHODN NPs) were formulated by self assembled method using various N/P ratios (moles ratio of amine groups of CH to phosphate moieties of ODNs; 0.5:1, 1:1, 3:1, 5:1 and 7:1) of CH to ODN. The developed CHODN NPs were evaluated with respect to gel retardation assay, particle size, zeta potential and cytotoxicity and transfection efficiency. Results: Complete complexation of CH/ODN was achieved at the charge ratio of 0.5:1 or above and CHODN NPs displayed resistance against DNase I. On increasing the N/P ratio of CH/ODN, particle size of the NPs decreased whereas zeta potential (ZV) value increased. No significant toxicity was observed at all CH concentrations. The transfection efficiency was increased on increasing N/P ratio from 1:1 to 3:1, whereas it was decreased with further increment in N/P ratio upto 7:1. Maximum transfection of CHODN NPs with both the cell lines (Raw 267.4 cells and Hela cells) was achieved at N/P ratio of 3:1. The results suggest that transfection efficiency of CHODN NPs is dependent on N/P ratio. Conclusion: Thus the present study states that LMW chitosan nanoparticulate carriers would be acceptable choice to improve transfection efficiency in vitro as well as in vivo delivery of oligonucleotide.

Keywords: LMW-chitosan, chitosan nanoparticles, biocompatibility, cytotoxicity study, transfection efficiency, oligonucleotide

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Authors: Charalampos N. Bompas, Eleni Poulou-Sidiropoulou, Martina Samiotaki, Alexios Vlamis-Gardikas

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Ιn all living organisms, antioxidant defenses are orchestrated by the thioredoxin (Trx) and glutaredoxin (Grx) systems. The Trx system of Escherichia coli (E. coli) is comprised of Trx1 and Trx2, both reduced by thioredoxin reductase (TrxR). The Grx system consists of four Grxs (Grx1, Grx2, Grx3, and Grx4), all reduced by glutathione (GSH) except for Grx4, which is reduced by TrxR. Under normal conditions, the GSH reductase of the Grx system keeps GSH at its reduced state. NADPH+ provides the electrons for all reductions in the Trx and Grx systems. Although the role of the E. coli Trx system is widely known, the function of the Grx system reflects the main property of Grx1, which is the reduction of ribonucleotide reductase Ia (RRIa). E. coli Grx3 (encoded by grxC) may also reduce RRIa in vitro but with slow kinetics. The molecule may account for up to 0.4% of total soluble protein and has been the subject of extensive structural studies. Its biological function, however, remains unknown. Herein, affinity chromatography with monothiol Grx3 serving as bait was used to detect the interactions of Grx3 with other proteins. Different types of interactions were identified (covalent, weak, and strong non-covalent) that suggested novel functions for Grx3. In silico approaches were employed to validate selected interactions. In addition, total protein extracts from the null mutant for grxC and the wild-type strain were compared. The overall findings suggest that Grx3 is involved in various metabolic processes, protein synthesis, and stress responses, expanding the recognized functions of Grx3 beyond the possible reduction of RRIa.

Keywords: escherichia coli, glutaredoxin 3, interactome, thiol-disulfide oxidoreductase

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