Search results for: interferon alpha and beta receptor subunit 2

Authors: Hamed Alizadeh Dashagholi, Hossein Yousefi-Banaem, Mina Naeimi

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Current study established for EEG signal analysis in patients with language disorder. Language disorder can be defined as meaningful delay in the use or understanding of spoken or written language. The disorder can include the content or meaning of language, its form, or its use. Here we applied Z-score, power spectrum, and coherence methods to discriminate the language disorder data from healthy ones. Power spectrum of each channel in alpha, beta, gamma, delta, and theta frequency bands was measured. In addition, intra hemispheric Z-score obtained by scoring algorithm. Obtained results showed high Z-score and power spectrum in posterior regions. Therefore, we can conclude that peoples with language disorder have high brain activity in frontal region of brain in comparison with healthy peoples. Results showed that high coherence correlates with irregularities in the ERP and is often found during complex task, whereas low coherence is often found in pathological conditions. The results of the Z-score analysis of the brain dynamics showed higher Z-score peak frequency in delta, theta and beta sub bands of Language Disorder patients. In this analysis there were activity signs in both hemispheres and the left-dominant hemisphere was more active than the right.

Keywords: EEG, electroencephalography, coherence methods, language disorder, power spectrum, z-score

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Authors: N. Fuad, M. N. Taib, R. Jailani, M. E. Marwan

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In this paper, the comparison between k-Nearest Neighbor (kNN) algorithms for classifying the 3D EEG model in brain balancing is presented. The EEG signal recording was conducted on 51 healthy subjects. Development of 3D EEG models involves pre-processing of raw EEG signals and construction of spectrogram images. Then, maximum PSD values were extracted as features from the model. There are three indexes for the balanced brain; index 3, index 4 and index 5. There are significant different of the EEG signals due to the brain balancing index (BBI). Alpha-α (8–13 Hz) and beta-β (13–30 Hz) were used as input signals for the classification model. The k-NN classification result is 88.46% accuracy. These results proved that k-NN can be used in order to predict the brain balancing application.

Keywords: power spectral density, 3D EEG model, brain balancing, kNN

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Authors: Sila Akhan, Muge Toygar, Murat Sayan, Simge Fidan

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Chronic viral hepatitis B, C, and D can cause hepatocellular carcinoma (HCC), cirrhosis and death. The proper treatment reduce the risk of development of HCC importantly, but not to zero point. Materials and Methods: We analysed retrospectively our chronic viral hepatitis B, C and D patients who attended to our Infectious Diseases policlinic between 2004-2018. From 589 biopsy-proven chronic hepatitis patients 3 have hepatocellular carcinoma on our follow up. First case is 74 years old patient. His HCV infection diagnosis was made 8 years ago. First treatment was pegylated interferon plus ribavirin only 28 weeks, because of HCV RNA breakthrough under treatment. In 2013 he was retreated with telaprevir, pegylated interferon plus ribavirin 24 weeks. But at the end of the therapy HCV RNA was found 1.290.000 IU/mL. He has abdominal ultrasonography (US) controls and alpha-fetoprotein (AFP) at 6 months intervals. All seemed normal until 2015 then he has an abdominal magnetic resonance imaging (MRI) and found HCC by chance. His treatment began in Oncology Clinic after verified with biopsy of HCC. And then sofosbuvir/ledipasvir was given to him for HCV 24 weeks. Sustained virologic response (SVR) was obtained. He is on cure for HCV infection and under control of Oncology for HCC. Second patient is 36 years old man. He knows his HBV infection since 2008. HBsAg and HBeAg positive; HDV RNA negative. Liver biopsy revealed grade:4, stage 3-4 according modified Knodell scoring system. In 2010 tenofovir treatment was began. His abdominal US and AFP were normal. His controls took place at 6 months intervals and HBV DNA negative, US, and AFP were normal until 2016 continuously. AFP found 37 above the normal range and then HCC was found in MRI. Third patient is 57 years old man. As hepatitis B infection was first diagnosed; he has cirrhosis and was began tenofovir as treatment. In short time he has HCC despite normal AFP values. Conclusion: In Mediterranian countries including Turkey naturally occurring pre-S/S variants are more than 75% of all chronic hepatitis B patients. This variants may contribute to the development of progressive liver damage and hepatocarcinogenesis. HCV-induced development of HCC is a gradual process and is affected by the duration of disease and viral genotype. All the chronic viral hepatitis patients should be followed up in 6 months intervals not only with US and AFP for HCC. Despite they have proper treatment there is always the risk development of HCC. Chronic hepatitis patients cannot be dropped from follow up even treated well.

Keywords: HCC, HCV, HBV, DAA

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Authors: Yasser M. Saad, Heba El-Sebaie Abd El-Sadek

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Some Metapenaeus monoceros cox1 gene fragments were isolated, purified, sequenced, and comparatively analyzed with some other Crustacean Cox1 gene sequences (obtained from National Center for Biotechnology Information). This work was designed for testing the efficiency of this system in reconstruction of phylogenetic relations among some Crustacean species belonging to four genera (Metapenaeus, Artemia, Daphnia and Calanus). The single nucleotide polymorphism and haplotype diversity were calculated for all estimated mt-DNA fragments. The genetic distance values were 0.292, 0.015, 0.151, and 0.09 within Metapenaeus species, Calanus species, Artemia species, and Daphnia species, respectively. The reconstructed phylogenetic tree is clustered into some unique clades. Cytochrome oxidase subunit 1 gene (cox1) was a powerful system in reconstruction of phylogenetic relations among evaluated crustacean species.

Keywords: crustaceans, genetics, Cox1, phylogeny

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Authors: Daina Jonkus, Solvita Petrovska, Dace Smiltina, Lasma Cielava

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The beta-lactoglobulin and kappa-casein are milk proteins which are important for milk composition. Cows with beta-lactoglobulin and kappa-casein gene BB genotypes have highest milk crude protein and fat content. The aim of the study was to determinate the frequencies of milk protein gene polymorphisms in local Latvian Brown (LB) cows breed and analyze the influence of beta-lactoglobulin and kappa-casein genotypes to milk productivity traits. 102 cows’ genotypes of milk protein genes were detected using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP) and electrophoresis on 3% agarose gel. For beta-lactoglobulin were observed 2 types of alleles A and B and for kappa-casein 3 types: A, B and E. Highest frequency in beta-lactoglobulin gene was observed for B allele – 0.926. Molecular analysis of beta-lactoglobulin gene shows 86.3% of individuals are homozygous by B allele and animals are with genotypes BB and 12.7% of individuals are heterozygous with genotypes AB. The highest milk yield 4711.7 kg was for 1st lactation cows with AB genotypes, whereas the highest milk protein content (3.35%) and fat content (4.46 %) was for BB genotypes. Analysis of the kappa-casein locus showed a prevalence of the A allele – 0.750. The genetic variant of B was characterized by a low frequency – 0.240. Moreover, the frequency of E occurred in the LB cows’ population with very low frequency – 0.010. 54.9 % of cows are homozygous with genotypes AA, and only 4.9 % are homozygous with genotypes BB. 32.8 % of individuals are heterozygous with genotypes AB, and 2.0 % are with AE. The highest milk productivity was for 1st lactation cows with AB genotypes: milk yield 4620.3 kg, milk protein content 3.39% and fat content 4.53 %. According to the results, in local Latvian brown there are only 2.9% of cows are with BB-BB genotypes, which is related to milk coagulation ability and affected cheese production yield. Acknowledgment: the investigation is supported by VPP 2014-2017 AgroBioRes Project No. 3 LIVESTOCK.

Keywords: beta-lactoglobulin, cows, genotype frequencies, kappa-casein

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Authors: Sintija Miļuna, Ričards Melderis, Loreta Briuka, Dagnija Rostoka, Ingus Skadiņš, Juta Kroiča

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Objectives Smokeless tobacco products in Latvia become more available and favorable to young adults, especially students and athletes like hockey and floorball players. The aim of the research was to detect visual mucosal changes in the oral cavity in smokeless tobacco users and to evaluate pro - inflammatory and anti - inflammatory cytokine (IL-6, IL-1, IL-8, TNF Alpha) levels in saliva from smokeless tobacco users. Methods A smokeless tobacco group (n=10) and a control group (non-tobacco users) (n=10) were intraorally examined for oral lesions and 5 ml of saliva were collected. Saliva was analysed for Il-6, IL-1, Il-8, TNF Alpha using ELISA Sigma-Aldrich. For statistical analysis IBM Statistics 27 was used (Mann - Whitney U test, Spearman’s Rank Correlation coefficient). This research was approved by the Ethics Committee of Rīga Stradiņš University No.22/28.01.2016. This research has been developed with financing from the European Social Fund and Latvian state budget within the project no. 8.2.2.0/20/I/004 “Support for involving doctoral students in scientific research and studies” at Rīga Stradiņš University. Results IL-1, IL-6, IL-8, TNF Alpha levels were higher in the smokeless tobacco group (IL-1 83.34 pg/ml vs. 74.26 pg/ml; IL-6 195.10 pg/ml vs. 6.16 pg/ml; IL-8 736.34 pg/ml vs. 285.26 pg/ml; TNF Alpha 489.27 pg/ml vs. 200.9 pg/ml), but statistically there is no difference between control group and smokeless tobacco group (IL1 p=0.190, IL6 p=0.052, IL8 p=0.165, TNF alpha p=0.089). There was statistical correlation between IL1 and IL6 (p=0.023), IL6 and TNF alpha (p=0.028), IL8 and IL6 (p=0.005). Conclusions White localized lesions were detected in places where smokeless tobacco users placed sachets. There is a statistical correlation between IL6 and IL1 levels, IL6 and TNF alpha levels, IL8 and IL6 levels in saliva. There are no differences in the inflammatory cytokine levels between control group and smokeless tobacco group.

Keywords: smokeless tobacco, Snus, inflammatory biomarkers, oral lesions, oral pathology

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Authors: Zahra Asgar Pour

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Two types of Ti-Al-containing zeolitic beads with an average diameter of 450 to 750 µm and hierarchical porosity were synthesized using a hard template method and tested as heterogeneous catalysts in the epoxidation of cycloalkenes (i.e. cyclohexene and cis-cyclooctene) with aqueous hydrogen peroxide (H₂O₂) or tert-butyl hydroperoxide(TBHP) as the oxidant agent. The first type of zeolitic beads was prepared by hydrothermal treatment of a primarygel (containing the Si, Ti, and Al precursors) in the presence of porous anion-exchange resin beads as the hard shaping template. After calcination, these beads (Ti-Al-Beta-HDT-B) consisted of both crystalline zeolite Beta and an amorphous silicate phase. The second type of zeolitic beads (Ti-Beta-PS-deAl-14.4-B) was obtained by post-synthesis dealumination of Al-containing zeolite Beta beads using 14.4 M HNO₃, followed by Ti grafting (3 wt% per gram of zeolite). The prepared materials were characterised by means of XRD, N2-physisorption, UV-vis, XRF, SEM, and TEM and tested as heterogeneous epoxidation catalysts. This post-synthetically prepared catalyst demonstrated higher activity (cyclohexene conversion of 22.7 % and epoxide selectivity of 33.5 %) after 5 h at60 °C, which emanates from the crystalline structure and higher degrees of hydrophobicity. In addition, the post-synthetically prepared beads were prone to partial Ti leaching in the presence of H₂O₂, whereas they showed to be resistant against Ti leaching using tert-butyl hydroperoxide as the oxidant agent.

Keywords: epoxidation, structured catalysts, hierarchical porosity, bead-shape catalysts

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Authors: Ali Kassem, Ehab Fawzy, Mahmoud Sef el-eslam, Fatma Salah- Eldeen, El zahraa Mohamed

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Introduction: The combination of interferon (INF) and ribavirin is the preferred treatment for chronic hepatitis C viral (HCV) infection. However, nonresponse to this therapy remains common and is associated with several factors such as HCV genotype and HCV viral load in addition to host factors such as sex, HLA type and cytokine polymorphisms. Aim of the work: The aim of this study was to determine predictors of response to (INF) therapy in chronic HCV infected patients treated with INF alpha and ribavirin combination therapy. Patients and Methods: The present study included 110 patients (62 males, 48 females) with chronic HCV infection. Their ages ranged from 20-59 years. Inclusion criteria were organized according to the protocol of the Egyptian National Committee for control of viral hepatitis. Patients included in this study were recruited to receive INF ribavirin combination therapy; 54 patients received pegylated NF α-2a (180 μg) and weight based ribavirin therapy (1000 mg if < 75 kg, 1200 mg if > 75 kg) for 48 weeks and 53 patients received pegylated INF α-2b (1.5 ug/kg/week) and weight based ribavirin therapy (800 mg if < 65 kg, 1000 mg if 65-75 kg and 1200 mg if > 75kg). One hundred and seven liver biopsies were included in the study and submitted to histopathological examination. Hematoxylin and eosin (H&E) stained sections were done to assess both the grade and the stage of chronic viral hepatitis, in addition to the degree of steatosis. Modified hepatic activity index (HAI) grading, modified Ishak staging and Metavir grading and staging systems were used. Laboratory follow up including: HCV PCR at the 12th week to assess the early virologic response (EVR) and at the 24th week were done. At the end of the course: HCV PCR was done at the end of the course and tested 6 months later to document end virologic response (ETR) and sustained virologic response (SVR) respectively. Results One hundred seven patients; 62 males (57.9 %) and 45 females (42.1%) completed the course and included in this study. The age of patients ranged from 20-59 years with a mean of 40.39±10.03 years. Six months after the end of treatment patients were categorized into two groups: Group (1): patients who achieved sustained virological response (SVR). Group (2): patients who didn't achieve sustained virological response (non SVR) including non-responders, breakthrough and relapsers. In our study, 58 (54.2%) patients showed SVR, 18 (16.8%) patients were non-responders, 15 (14%) patients showed break-through and 16 (15 %) patients were relapsers. Univariate binary regression analysis of the possible risk factors of non SVR showed that the significant factors were higher age, higher fasting insulin level, higher Metavir stage and higher grade of hepatic steatosis. Multivariate binary regression analysis showed that the only independent risk factor for non SVR was high fasting insulin level. Conclusion: Younger age, lower Metavir stage, lower steatosis grade and lower fasting insulin level are good predictors of SVR and could be used in predicting the treatment response of pegylated interferon/ribavirin therapy.

Keywords: chronic HCV infection, interferon ribavirin combination therapy, predictors to antiviral therapy, treatment response

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Authors: Daniel Assefa, Engeda Dessalegn, Chetan Chauhan

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Moringa stenopetala is a socioeconomic valued tree that is widely available and cultivated in the Southern part of Ethiopia. The leaves have been traditionally used as a food source with high nutritional and medicinal values. The present work was carried out to evaluate the effect of thermal treatment on the total phenolic content, antioxidant and alpha-amylase inhibition activities of aqueous leaf extracts during maceration and different decoction time interval (5, 10 and 15 min). The total phenolic content was determined by the Folin-ciocalteu methods whereas antioxidant activities were determined by 2,2-diphenyl-1-picryl-hydrazyl(DPPH) radical scavenging, reducing power and ferrous ion chelating assays and alpha-amylase inhibition activity was determined using 3,5-dinitrosalicylic acid method. Total phenolic content ranged from 34.35 to 39.47 mgGAE/g. Decoction for 10 min extract showed ferrous ion chelating (92.52), DPPH radical scavenging (91.52%), alpha-amylase inhibition (69.06%) and ferric reducing power (0.765), respectively. DPPH, reducing power and alpha-amylase inhibition activities showed positive linear correlation (R2=0.853, R2= 0.857 and R2=0.930), respectively with total phenolic content but ferrous ion chelating activity was found to be weakly correlated (R2=0.481). Based on the present investigation, it could be concluded that major loss of total phenolic content, antioxidant and alpha-amylase inhibition activities of the crude leaf extracts of Moringa stenopetala leaves were observed at decoction time for 15 min. Therefore, to maintain the total phenolic content, antioxidant, and alpha-amylase inhibition activities of leaves, cooking practice should be at the optimum decoction time (5-10 min).

Keywords: alpha-amylase inhibition, antioxidant, Moringa stenopetala, total phenolic content

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Authors: Mengying Wang, Dongjing Liu, Holger Schwender, Ping Wang, Hongping Zhu, Tao Wu, Terri H Beaty

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Background: Maternal smoking is a recognized risk factor for nonsyndromic cleft lip with or without cleft palate (NSCL/P). It has been reported that the effect of maternal smoking on oral clefts is mediated through genes that influence nicotine dependence. The polymorphisms of cholinergic receptor nicotinic alpha (CHRNA) and beta (CHRNB) subunits genes have previously shown strong associations with nicotine dependence. Here, we attempted to investigate whether the above genes are associated with clefting risk through testing for potential gene-gene (G×G) and gene-environment (G×E) interaction. Methods: We selected 120 markers in 14 genes associated with nicotine dependence to conduct transmission disequilibrium tests among 806 Chinese NSCL/P case-parent trios ascertained in an international consortium which conducted a genome-wide association study (GWAS) of oral clefts. We applied Cordell’s method using “TRIO” package in R to explore G×G as well as G×E interaction involving environmental tobacco smoke (ETS) based on conditional logistic regression model. Results: while no SNP showed significant association with NSCL/P after Bonferroni correction, we found signals for G×G interaction between 10 pairs of SNPs in CHRNA3, CHRNA5, and CHRNB4 (p<10-8), among which the most significant interaction was found between RS3743077 (CHRNA3) and RS11636753 (CHRNB4, p<8.2×10-12). Linkage disequilibrium (LD) analysis revealed only low level of LD between these markers. However, there were no significant results for G×ETS interaction. Conclusion: This study fails to detect association between nicotine dependence genes and NSCL/P, but illustrates the importance of taking into account potential G×G interaction for genetic association analysis in NSCL/P. This study also suggests nicotine dependence genes should be considered as important candidate genes for NSCL/P in future studies.

Keywords: Gene-Gene Interaction, Maternal Smoking, Nicotine Dependence, Non-Syndromic Cleft Lip with or without Cleft Palate

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Authors: Shraddha Rane, Richard Warren, Stephen Eyre

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L-23 is a pro-inflammatory molecule that signals T cells to release cytokines such as IL-17A and IL-22. Psoriasis is driven by a dysregulated immune response, within which IL-23 is now thought to play a key role. Genome-wide association studies (GWAS) have identified a number of genetic risk loci that support the involvement of IL-23 signalling in psoriasis; in particular a robust susceptibility locus at a gene encoding a subunit of the IL-23 receptor (IL23R) (Stuart et al., 2015; Tsoi et al., 2012). The lead psoriasis-associated SNP rs9988642 is located approximately 500 bp downstream of IL23R but is in tight linkage disequilibrium (LD) with a missense SNP rs11209026 (R381Q) within IL23R (r2 = 0.85). The minor (G) allele of rs11209026 is present in approximately 7% of the population and is protective for psoriasis and several other autoimmune diseases including IBD, ankylosing spondylitis, RA and asthma. The psoriasis-associated missense SNP R381Q causes an arginine to glutamine substitution in a region of the IL23R protein between the transmembrane domain and the putative JAK2 binding site in the cytoplasmic portion. This substitution is expected to affect the receptor’s surface localisation or signalling ability, rather than IL23R expression. Recent studies have also identified a psoriatic arthritis (PsA)-specific signal at IL23R; thought to be independent from the psoriasis association (Bowes et al., 2015; Budu-Aggrey et al., 2016). The lead PsA-associated SNP rs12044149 is intronic to IL23R and is in LD with likely causal SNPs intersecting promoter and enhancer marks in memory CD8+ T cells (Budu-Aggrey et al., 2016). It is therefore likely that the PsA-specific SNPs affect IL23R function via a different mechanism compared with the psoriasis-specific SNPs. It could be hypothesised that the risk allele for PsA located within the IL23R promoter causes an increase IL23R expression, relative to the protective allele. An increased expression of IL23R might then lead to an exaggerated immune response. The independent genetic signals identified for psoriasis and PsA in this locus indicate that different mechanisms underlie these two conditions; although likely both affecting the function of IL23R. It is very important to further characterise these mechanisms in order to better understand how the IL-23 receptor and its downstream signalling is affected in both diseases. This will help to determine how psoriasis and PsA patients might differentially respond to therapies, particularly IL-23 biologics. To investigate this further we have developed an in vitro model using CD4 T cells which express either wild type IL23R and IL12Rβ1 or mutant IL23R (R381Q) and IL12Rβ1. Model expressing different isotypes of IL23R is also underway to investigate the effects on IL23R expression. We propose to further investigate the variants for Ps and PsA and characterise key intracellular processes related to the variants.

Keywords: IL23R, psoriasis, psoriatic arthritis, SNP

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Authors: Ryan M. Monti, Bijal Mehta

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In cases of massive pulmonary embolism, defined as acute pulmonary embolism presenting with systemic hypotension or right ventricular dysfunction and impending failure, there is indication that unconventional therapies, such as phosphodiesterase inhibitors, endothelin receptor antagonists, and/or prostacyclin analogs may decrease the morbidity and mortality. Based on the premise that dilating the pulmonary artery will decrease the pulmonary vascular pressure, while simultaneously decreasing the aggregation of platelets, it can be hypothesized that increased blood flow through the pulmonary artery will decrease right heart strain and subsequent morbidity and mortality. While this theory has yet to be formally studied, the recommendations for treating massive pulmonary embolism with phosphodiesterase inhibitors, endothelin receptor antagonists, and/or prostacyclin analogs in conjunction with the current standards of care in massive pulmonary embolism should be formally studied. In particular, patients with massive PE who are unable to undergo thrombolysis/surgical intervention may be the ideal population to study the use of these treatments to determine any decrease in mortality and morbidity (short term and long term).

Keywords: acute pulmonary thromboembolism, treatment of pulmonary embolism, use of phosphodiesterase inhibitors, endothelin receptor antagonists, prostacyclin analogs in PE

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Authors: Andreina Giustiniani, Massimiliano Oliveri

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Rhythmic activity in different frequencies could subserve distinct functional roles during visual perception and visual mental imagery. In particular, alpha band activity is thought to play a role in active inhibition of both task-irrelevant regions and processing of non-relevant information. In the present blind placebo-controlled study we applied alpha transcranial alternating current stimulation (tACS) in the occipital cortex both during a basic visual perception and a visual working memory task. To understand if the role of alpha is more related to a general inhibition of distractors or to an inhibition of task-irrelevant regions, we added a non visual distraction to both the tasks.Sixteen adult volunteers performed both a simple perception and a working memory task during 10 Hz tACS. The electrodes were placed over the left and right occipital cortex, the current intensity was 1 mA peak-to-baseline. Sham stimulation was chosen as control condition and in order to elicit the skin sensation similar to the real stimulation, electrical stimulation was applied for short periods (30 s) at the beginning of the session and then turned off. The tasks were split in two sets, in one set distracters were included and in the other set, there were no distracters. Motor interference was added by changing the answer key after subjects completed the first set of trials.The results show that alpha tACS improves working memory only when no motor distracters are added, suggesting a role of alpha tACS in inhibiting non-relevant regions rather than in a general inhibition of distractors. Additionally, we found that alpha tACS does not affect accuracy and hit rates during the visual perception task. These results suggest that alpha activity in the occipital cortex plays a different role in perception and working memory and it could optimize performance in tasks in which attention is internally directed, as in this working memory paradigm, but only when there is not motor distraction. Moreover, alpha tACS improves working memory performance by means of inhibition of task-irrelevant regions while it does not affect perception.

Keywords: alpha activity, interference, perception, working memory

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Authors: Merve Cebi, Turker Tekin Erguzel, Gokben Hizli Sayar

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Understanding the biological mechanisms of dissociation in patients with bipolar disorder is important for developing new treatment approaches for the disorder as well as using the appropriate treatment strategies. In this study, we compared EEG power and coherence values for alpha, theta and beta frequency bands between patients having bipolar disorder with dissociation as compared to the bipolar patients without dissociation. Accordingly, we did not find any statistically significant difference in either the absolute or the relative power between the groups. Coherence values were not found to be statistically different, as well. Therefore, our results demonstrated that the existence of dissociation did not influence electrophysiological correlates in bipolar disorder.

Keywords: bipolar disorder, dissociation, absolute power, coherence

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Authors: Arthur C. Tsai, Chii-Shyang Kuo, Vincent S. C. Chien, Michelle Liou, Philip E. Cheng

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Meditation enhances mental abilities and it is an antidote to anxiety. However, very little is known about brain mechanisms and cortico-subcortical interactions underlying meditation-induced anxiety relief. In this study, the changes of phase-amplitude coupling (PAC) in which the amplitude of the beta frequency band were modulated in phase with delta rhythm were investigated after eight-week of meditation training. The study hypothesized that through a concentrate but relaxed mental training the delta-beta coupling in the frontal regions is attenuated. The delta-beta coupling analysis was applied to within and between maximally-independent component sources returned from the extended infomax independent components analysis (ICA) algorithm on the continuous EEG data during mediation. A unique meditative concentration task through relaxing body and mind was used with a constant level of moderate mental effort, so as to approach an ‘emptiness’ meditative state. A pre-test/post-test control group design was used in this study. To evaluate cross-frequency phase-amplitude coupling of component sources, the modulation index (MI) with statistics to calculate circular phase statistics were estimated. Our findings reveal that a significant delta-beta decoupling was observed in a set of frontal regions bilaterally. In addition, beta frequency band of prefrontal component were amplitude modulated in phase with the delta rhythm of medial frontal component.

Keywords: phase-amplitude coupling, ICA, meditation, EEG

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Authors: Azlina Binti Abu Bakar, Fahmi Zaidi Bin Abdul Razak, Wan Salihin Wong Abdullah

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Psychographic is a psychological study of values, attitudes, interests and it is used mostly in prediction, opinion research and social research. This study predicts the influence of performance expectancy, effort expectancy, social influence and facilitating condition on e-government acceptance among Malaysian citizens. The survey responses of 543 e-government users have been validated and analyzed by means of covariance-based Structural Equation Modeling. The findings indicate that e-government acceptance among Malaysian citizens are mainly influenced by performance expectancy (β = 0.66, t = 11.53, p < 0.01) and social influence (β = 0.20, t = 4.23, p < 0.01). Surprisingly, there is no significant effect of facilitating condition and effort expectancy on e-government continuance intention (β = 0.01, t = 0.27, p > 0.05; β = -0.01, t = -0.40, p > 0.05). This study offers government and vendors a frame of reference to analyze citizen’s situation before initiating new innovations. In case of Malaysian e-government technology, adoption strategies should be built around fostering level of citizens’ technological expectation and social influence on e-government usage.

Keywords: continuance intention, Malaysian citizen, media psychology, structural equation modeling

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Authors: Fiston Masudi Tambwe, Lwanga Charles, Arfang Badji, Unzimai Innocent

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The development of maize varieties combining Provitamin A (PVA), high yield, and Striga resistance is an effective and affordable strategy to contribute to food security in sub-Saharan Africa, where maize is a staple food crop. There has been limited research on introgressing PVA genes into Striga-resistant maize genotypes. The objectives of this study were to: i) determine the mode of gene action controlling PVA carotenoid accumulation in Striga-resistant maize, ii) identify Striga-resistant maize hybrids with high PVA content and stable yield, and iii) validate the presence of PVA functional markers in offspring. Six elite, Striga-resistant inbred females were crossed with six high-PVA inbred males in a North Carolina Design II and their offspring were evaluated in four environments, following a 5x8 alpha lattice design with four hybrid checks. Results revealed that both additive and non-additive gene action control carotenoid accumulation in the present study, with a predominance of non-additive gene effects for PVA. Hybrids STR1004xCLHP0352 and STR1004xCLHP0046 - identified as Striga-resistant because they supported fewer Striga plants – were the highest-yielding genotypes with a moderate PVA concentration of 5.48 and 5.77 µg/g, respectively. However, those two hybrids were not stable in terms of yield across all environments. Hybrid STR1007xCLHP0046, however, supported fewer Striga plants, had a yield of 4.52 T/ha, a PVA concentration of 4.52 µg/g, and was also stable. Gel-based marker systems of CrtRB1 and LCYE were used to screen the hybrids and favorable alleles of CrtRB1 primers were detected in 20 hybrids, confirming good levels of PVA carotenoids. Hybrids with favorable alleles of LCYE had the highest concentration of non-PVA carotenoids. These findings will contribute to the development of high-yielding PVA-rich maize varieties in Uganda.

Keywords: gene action, stability, striga resistance, provitamin A markers, beta-carotene hydroxylase 1, CrtRB1, beta-carotene, beta-cryptoxanthin, lycopene epsilon cyclase, LCYE

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Authors: Nagasamy Venkatesh Dhandapani, Amged Awad El-Gied

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Cefixime, a BCS class II drug, is insoluble in water but freely soluble in acetone and in alcohol. The aqueous solubility of cefixime in water is poor and exhibits exceptionally slow and intrinsic dissolution rate. In the present study, cefixime and β-Cyclodextrin (β-CD) solid dispersions were prepared with a view to study the effect and influence of β-CD on the solubility and dissolution rate of this poorly aqueous soluble drug. Phase solubility profile revealed that the solubility of cefixime was increased in the presence of β-CD and was classified as A_L-type. Effect of variable, such as drug:carrier ratio, was studied. Physical characterization of the solid dispersion was characterized by Fourier transform infrared spectroscopy (FT-IR) and Differential scanning calorimetry (DSC). These studies revealed that a distinct loss of drug crystallinity in the solid molecular dispersions is ostensibly accounting for enhancement of dissolution rate in distilled water. The drug release from the prepared solid dispersion exhibited a first order kinetics. Solid dispersions of cefixime showed a 6.77 times fold increase in dissolution rate over the pure drug.

Keywords: β-cyclodextrin, cefixime, dissolution, Kneading method, solid dispersions, release kinetics

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Authors: Su Bin Wang, Jin Hee Ahn, Tong-Shin Chang

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The peroxisome proliferator-activated receptors (PPARs) are member of nuclear receptor superfamily that act as a ligand-activated transcription factors. Although platelets lack a nucleus, previous studies have shown that PPARγ agonists, rosiglitazone, inhibited platelet activation induced by collagen. In this study, we investigated the inhibitory effects of KR-62980, a newly synthesized PPARγ agonist, on collagen receptor-stimulated platelet activation. The specific tyrosine phosphorylations of key components (Syk, Vav1, Btk and PLCγ2) for collagen receptor signaling pathways were suppressed by KR-62980. KR-62980 also attenuated downstream responses including cytosolic calcium elevation, P-selectin surface exposure, and integrin αIIbβ3 activation. PPARγ was found to associate with multiple proteins within the LAT signaling complex in collagen-stimulated platelets. This association was prevented by KR-62980, indicating a potential mechanism for PPARγ function in collagen-stimulated platelet activation. Furthermore, KR-62980 inhibited platelet aggregation and adhesion in response to collagen in vitro and prolonged in vivo thrombotic response in carotid arteries of mice. Collectively, these data suggest that KR-62980 inhibits collagen-stimulated platelet activation and thrombus formation through modulating the collagen receptor signaling pathways.

Keywords: KR-62980, PPARγ, antiplatelet, thrombosis

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Authors: Frida Carrillo Morales, Maria Maricela Carrasco Yépez, Saúl Rojas Hernández

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Naegleria fowleri is the causative agent of primary amebic meningoencephalitis, this disease is acute and fulminant that affects humans. It has been reported that despite the existence of therapeutic options against this disease, its mortality rate is 97%. Therefore, the need arises to have vaccines that confer protection against this disease and, in addition to developing adjuvants to enhance the immune response. In this regard, in our work group, we obtained a peptide designed from the membrane protein MP2CL5 of Naegleria fowleri called Smp145 that was shown to be immunogenic; however, it would be of great importance to enhance its immunological response, being able to co-administer it with a non-toxic adjuvant. Therefore, the objective of this work was to carry out the bioinformatic design of a peptide of the Naegleria fowleri membrane protein MP2CL5 conjugated with a non-toxic modified adjuvant from the native A1 structure of Cholera Toxin. For which different bioinformatics tools were used to obtain a model with a modification in amino acid 61 of the A1 subunit of the CT (CTA1), to which the Smp145 peptide was added and both molecules were joined with a 13-glycine linker. As for the results obtained, the modification in CTA1 bound to the peptide produces a reduction in the toxicity of the molecule in in silico experiments, likewise, the prediction in the binding of Smp145 to the receptor of B cells suggests that the molecule is directed in specifically to the BCR receptor, decreasing its native enzymatic activity. The stereochemical evaluation showed that the generated model has a high number of adequately predicted residues. In the ERRAT test, the confidence with which it is possible to reject regions that exceed the error values was evaluated, in the generated model, a high score was obtained, which determines that the model has a good structural resolution. Therefore, the design of the conjugated peptide in this work will allow us to proceed with its chemical synthesis and subsequently be able to use it in the mouse meningitis protection model caused by N. fowleri.

Keywords: immunology, vaccines, pathogens, infectious disease

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Authors: Matt Vellkorn, Mara Sarinski

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The field of advanced diagnostics is a very rapidly changing one. A new technology that has not been fully used yet are resistotrons. A resistotron is a physical device thatis used to detect the presence of low energy alpha particles. It has been used for many years in nuclear physics as an alpha particle detector. Since they are used in nuclear physics, they have to be accurate. They have to be able to differentiate between alpha particles and other types of radiation. The resistotrons are primarily used for safety. They are used in areas where people or animals can get exposed to radiation. A typical example is in the treatment of nuclear waste. As it is with any nuclear physics instrument, a resistotron has to be very accurate and reliable. In the past, the instrument was very expensive because they were made out of copper. Today, they are made out of brass. The main difference is that brass is much less expensive than copper.

Keywords: biosensors, resistotrons, biophysics, diagnostics

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Authors: Latifeh Navidpour, Shabnam Shabani, Alireza Heidari, Manouchehr Bashiri, Azadeh Ebrahim-Habibi, Soraya Shahhosseini, Hamed Shafaroodi, Sayyed Abbas Tabatabai, Mahsa Toolabi

Abstract:

A new series of 5-(2-aryloxy-4-nitrophenyl)-4H-1,2,4-triazoles and 5-(2-aryloxy-3-pyridyl)-4H-1,2,4-triazoles, possessing C-3 thio or alkylthio substituents, was synthesized and evaluated for their benzodiazepine receptor affinity and anti-seizure activity. These analogues revealed similar to significantly superior affinity to GABAA/ benzodiazepine receptor complex (IC50 values of 0.04–4.1 nM), relative to diazepam as the reference drug (IC50 value of 2.4 nM). To determine the onset of anti-seizure activity, the time-dependent effectiveness of i.p. administration of compounds on pentylenetetrazole induced seizure threshold was studied and a very good relationship was observed between the lipophilicity (cLogP) and onset of action of studied analogues (r2 = 0.964). The minimum effective dose of the compounds, determined at the time the analogues showed their highest activity, was demonstrated to be 0.025–0.1 mg/kg, relative to diazepam (0.025 mg/kg).

Keywords: 1, 2, 4-triazole, flexible benzodiazepines, GABAA/bezodiazepine receptor complex, onset of action, PTZ induced seizure threshold

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Authors: Jonas Colin

Abstract:

Standing at the vanguard of AI development, Alpha represents an unprecedented synthesis of logical rigor and human abstraction, meticulously crafted to mirror the user's unique persona and personality, a feat previously unattainable in AI development. Alpha, an avant-garde artefact in the realm of artificial intelligence, epitomizes a paradigmatic shift in personalized digital interaction, amalgamating user-specific dialogic patterns with the sophisticated algorithmic prowess of OpenAI's GPT-3.5 to engender a platform for enhanced metacognitive engagement and individualized user experience. Underpinned by a sophisticated algorithmic framework, Alpha integrates vast datasets through a complex interplay of neural network models and symbolic AI, facilitating a dynamic, adaptive learning process. This integration enables the system to construct a detailed user profile, encompassing linguistic preferences, emotional tendencies, and cognitive styles, tailoring interactions to align with individual characteristics and conversational contexts. Furthermore, Alpha incorporates advanced metacognitive elements, enabling real-time reflection and adaptation in communication strategies. This self-reflective capability ensures continuous refinement of its interaction model, positioning Alpha not just as a technological marvel but as a harbinger of a new era in human-computer interaction, where machines engage with us on a deeply personal and cognitive level, transforming our interaction with the digital world.

Keywords: chatbot, GPT 3.5, metacognition, symbiose

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Authors: Ayesha Waqar Khan, Mariam Altaf, Jamil Ahmad, Shaheen Shahzad

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Kidney fibrosis is an anticipated outcome of possibly all types of progressive chronic kidney disease (CKD). Epithelial-mesenchymal transition (EMT) signaling pathway is responsible for production of matrix-producing fibroblasts and myofibroblasts in diseased kidney. In this study, a discrete model of TGF-beta (transforming growth factor) and CTGF (connective tissue growth factor) was constructed using Rene Thomas formalism to investigate renal fibrosis turn over. The kinetic logic proposed by Rene Thomas is a renowned approach for modeling of Biological Regulatory Networks (BRNs). This modeling approach uses a set of constraints which represents the dynamics of the BRN thus analyzing the pathway and predicting critical trajectories that lead to a normal or diseased state. The molecular connection between TGF-beta, Smad 2/3 (transcription factor) phosphorylation and CTGF is modeled using GenoTech. The order of BRN is CTGF, TGF-B, and SMAD3 respectively. The predicted cycle depicts activation of TGF-B (TGF-β) via cleavage of its own pro-domain (0,1,0) and presentation to TGFR-II receptor phosphorylating SMAD3 (Smad2/3) in the state (0,1,1). Later TGF-B is turned off (0,0,1) thereby activating SMAD3 that further stimulates the expression of CTGF in the state (1,0,1) and itself turns off in (1,0,0). Elevated CTGF expression reactivates TGF-B (1,1,0) and the cycle continues. The predicted model has generated one cycle and two steady states. Cyclic behavior in this study represents the diseased state in which all three proteins contribute to renal fibrosis. The proposed model is in accordance with the experimental findings of the existing diseased state. Extended cycle results in enhanced CTGF expression through Smad2/3 and Smad4 translocation in the nucleus. The results suggest that the system converges towards organ fibrogenesis if CTGF remains constructively active along with Smad2/3 and Smad 4 that plays an important role in kidney fibrosis. Therefore, modeling regulatory pathways of kidney fibrosis will escort to the progress of therapeutic tools and real-world useful applications such as predictive and preventive medicine.

Keywords: CTGF, renal fibrosis signaling pathway, system biology, qualitative modeling

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Authors: Cyril Kaplan

Abstract:

26 participants played 4 EEG neurofeedback (NF) games encouraged to find their strategies to control the specific NF parameter. Mixed method analysis of performance in the games and post-session interviews led to the identification of states of consciousness that correlated with success in the game. We found that increase in left frontal beta activity was facilitated by evoking interest in observed surroundings, by wondering what is happening behind the window or what lies in a drawer in front.

Keywords: EEG neurofeedback, states of consciousness, frontal beta activity, mixed methods

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Authors: Roshika Tyagi, Shuvomoy Banerjee

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Among various diseases, cancer has become a huge threat to human beings globally. In the context of viral infection, Epstein–Barr virus (EBV) infection is ubiquitous in nature world-wide as well as in India. Recepteur d’Origine Nantais (RON) receptor tyrosine kinase is overexpressed in Lymphoblastoid cell lines (LCLs) but undetectable in primary B-cells. Biologically, RON expression was found to be essential for EBV transformed LCLs proliferation. In our study, we investigated whether EBV latent antigen EBNA3C is playing a crucial role in regulating RON receptor tyrosine kinase function in EBV-induced malignancies. Interestingly, we observed that expression pattern of RON was modulated by EBNA3C in EBV transformed LCLs compared with EBV negative BJAB cell line by PCR and western blot analysis. Moreover, in the absence of EBNA3C, RON expression was found low in western blot and immunofluorescence analysis and cell proliferation rate was significantly reduced in LCLs by cell viability assays. Therefore, our study clearly indicating the potential role of EBNA3C expressed in EBV-infected B-cells for modulating the functions of oncogenic kinases that leads to EBV induced B-cell transformation.

Keywords: apoptosis, cell proliferation, Epstein–barr virus, receptor tyrosine kinase

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Authors: Yuhua Wang, Mu Li, Jinggen Liu

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Aim: To investigate the different effects of heroin and milk in activating the corticostriatal system that plays a critical role in reward reinforcement learning. Methods: Male SD rats were trained daily for 15 d to self-administer heroin or milk tablets in a classic runway drug self-administration model. Immunohistochemical assay was used to quantify Arc protein expression in the medial prefrontal cortex (mPFC), the nucleus accumbens (NAc), the dorsomedial striatum (DMS) and the ventrolateral striatum (VLS) in response to chronic self-administration of heroin or milk tablets. NMDA receptor antagonist MK801 (0.1 mg/kg) or dopamine D1 receptor antagonist SCH23390 (0.03 mg/kg) were intravenously injected at the same time as heroin was infused intravenously. Results: Runway training with heroin resulted in robust enhancement of Arc expression in the mPFC, the NAc and the DMS on d 1, 7, and 15, and in the VLS on d 1 and d 7. However, runway training with milk led to increased Arc expression in the mPFC, the NAc and the DMS only on d 7 and/or d 15 but not on d 1. Moreover, runway training with milk failed to induce increased Arc protein in the VLS. Both heroin-seeking behavior and Arc protein expression were blocked by MK801 or SCH23390 administration. Conclusion: The VLS is likely to be critically involved in drug-seeking behavior. The NMDA and D1 receptor-dependent Arc expression is important in drug-seeking behavior.

Keywords: arc, mesocorticolimbic system, drug rewarding behavior, NMDA receptor

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Authors: Qiaoyue Kuang, Yang Li, Mizuki Endo, Takeaki Ozawa

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G protein-coupled receptors (GPCR) are the largest family of receptor proteins that detect molecules outside the cell and activate cellular responses. Of the GPCRs, dopamine receptors, which recognize extracellular dopamine, are essential to mammals due to their roles in numerous physiological events, including autonomic movement, hormonal regulation, emotions, and the reward system in the brain. To precisely understand the physiological roles of dopamine receptors, it is important to spatiotemporally control the signaling mediated by dopamine receptors, which is strongly dependent on their surface expression. Conventionally, chemical-induced interactions were applied to trigger the endocytosis of cell surface receptors. However, these methods were subjected to diffusion and therefore lacked temporal and special precision. To further understand the receptor-mediated signaling and to control the plasma membrane expression of receptors, an optogenetic tool called E-fragment was developed. The C-terminus of a light-sensitive photosensory protein cyptochrome2 (CRY2) was attached to β-Arrestin, and the E-fragment was generated by fusing the C-terminal peptide of vasopressin receptor (V2R) to CRY2’s binding partner protein CIB. The CRY2-CIB heterodimerization triggered by blue light stimulation brings β-Arrestin to the vicinity of membrane receptors and results in receptor endocytosis. In this study, the E-fragment system was applied to dopamine receptors 1 and 2 (DRD1 and DRD2) to control dopamine signaling. First, confocal fluorescence microscope observation qualitatively confirmed the light-induced endocytosis of E-fragment fused receptors. Second, NanoBiT bioluminescence assay verified quantitatively that the surface amount of E-fragment labeled receptors decreased after light treatment. Finally, GloSensor bioluminescence assay results suggested that the E-fragment-dependent receptor light-induced endocytosis decreased cAMP production in DRD1 signaling and attenuated the inhibition effect of DRD2 on cAMP production. The developed optogenetic tool was able to induce receptor endocytosis by external light, providing opportunities to further understand numerous physiological activities by controlling receptor-mediated signaling spatiotemporally.

Keywords: dopamine receptors, endocytosis, G protein-coupled receptors, optogenetics

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Authors: Kasi Viswanadh Matte, Abhisheh Kumar Mehata, M.S. Muthu

Abstract:

Brest cancer, up-regulated with human epidermal growth factor receptor type-2 (HER-2) led to the concept of developing HER-2 targeted anticancer therapeutics. Docetaxel-loaded D-α-tocopherol polyethylene glycol succinate 1000 conjugated chitosan (TPGS-g-chitosan) nanoparticles were prepared with or without Trastuzumab decoration. The particle size and entrapment efficiency of conventional, non-targeted and targeted nanoparticles were found to be in the range of 126-186 nm and 74-78% respectively. In-vitro, MDA-MB-231 cells showed that docetaxel-loaded non-targeted and HER-2 receptor targeted TPGS-g-chitosan nanoparticles have enhanced the cellular uptake and cytotoxicity with a promising bioadhesion property, in comparison to conventional nanoparticles. The IC50 values of non-targeted and targeted nanoparticles from cytotoxic assay were found to be 43 and 223 folds higher than DocelTM. The in-vivo pharmacokinetic study showed 2.33, and 2.82-fold enhancement in relative bioavailability of docetaxel for non-targeted and HER-2 receptor targeted nanoparticles, respectively than DocelTM, and after i.v administration, non-targeted and targeted nanoparticle achieved 3.48 and 5.94 times prolonged half-life in comparison to DocelTM. The area under the curve (AUC), relative bioavailability (FR) and mean residence time (MRT) were found to be higher for non-targeted and targeted nanoparticles compared to DocelTM. Further, histopathology results of non-targeted and targeted nanoparticles showed less toxicity on vital organs such as lungs, liver, and kidney compared to DocelTM.

Keywords: breast cancer, HER-2 receptor, targeted nanomedicine, chitosan, TPGS

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Authors: Ramazan F. Akkoc, Elif Erdem, Nalan Kaya, Gonca Ozan, D. Özlem Dabak, Enver Ozan

Abstract:

Maternal tobacco smoke exposure is known to cause growth retardation in the neonatal skeletal system. Alpha lipoic acid, a natural antioxidant found in some foods, limits the activities of osteoclasts and supports the osteoblast's bone formation mechanism. In this study, it was aimed to investigate the effects of alpha lipoic acid (ALA) on the height, long bones and tail lengths of pups exposed to maternal tobacco smoke. The rats were divided into four groups: 1) control group, 2) tobacco smoke group, 3) tobacco smoke + ALA group, and 4) ALA group. Rats in the group 2 (tobacco smoke), group 3 (tobacco smoke + ALA) were exposed to tobacco smoke twice a day for one hour starting from eight weeks before mating and during pregnancy. In addition to tobacco smoke, 20 mg/kg of alpha lipoic acid was administered via oral gavage to the rats in the group 3 (tobacco smoke + ALA). Only alpha lipoic acid was administered to the rats in the group 4. On day 21 postpartum, the height and tail lengths of the pups in all groups were measured, and the length of the extremity long bones was measured after decapitation. All morphometric measurements performed in group 2 (tobacco smoke) showed a significant decrease compared to group 1 (control), while all measurements in group 3 (tobacco smoke + ALA) showed a significant increase compared to group 2 (tobacco smoke). It has been shown that ALA has a protective effect against the regression of height, long bones and tail lengths of pups exposed to maternal tobacco smoke.

Keywords: alpha lipoic acid, bone, morphometry, rat, tobacco smoke

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