Search results for: serotonin receptors

Authors: S. Pradhan, D. Pradhan, G. Tripathy

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Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.

Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells

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Authors: Sukrat Sinha, Abhay Kumar, Shanthy Sundaram

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The Leishmania homologue of activated C kinase (LACK) is known T cell epitope from soluble Leishmania antigens (SLA) that confers protection against Leishmania challenge. This antigen has been found to be highly conserved among Leishmania strains. LACK has been shown to be protective against L. donovani challenge. A comprehensive analysis of several LACK sequences was completed. The analysis shows a high level of conservation, lower variability and higher antigenicity in specific portions of the LACK protein. This information provides insights for the potential consideration of LACK as a putative candidate in the context of visceral Leishmaniasis vaccine target.

Keywords: bioinformatics, genome assembly, leishmania activated protein kinase c (lack), next-generation sequencing

Procedia PDF Downloads 338

Authors: Rachid Mosbah, Aziez Chettoum, Zouhir Djerrou, Alberto Mantovani

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Selective serotonin reuptake inhibitors (SSRI) are a class of molecules used in treating depression, anxiety, and mood disorders. Paroxetine (PRT) is one of the mostly prescribed antidepressant which has attracted great attention regarding its side effects in recent years. This study was planned to assess the adverse effects of PRT on the biochemical parameters and reproductive system. Fourteen male Wistar rats were randomly allocated into two groups (7 rats or each): control and treated with PRT at dose of 5mg/kg.bw for two weeks. At the end of the experiment, blood was collected from retro orbital plexus for measuring the biochemical parameters, whereas the reproductive organs were removed for measuring semen quality and the histological investigations. Results showed that PRT induced significant changes in some biochemical parameters and alteration of semen quality including sperm count, spermatids number and sperm viability, motility, and abnormalities. The histopathological examinations of testis and epididymis revealed an alteration of spermatogenesis, cellular disorganization and vacuolization, enlargement of interstitial space, shrinkage and degenerative changes in the epithelium of seminiferous and epididymal tubules with few to nil numbers of spermatozoa in their lumen. In conclusion, PRT treatment caused changes in some biochemical parameters and sperm profile as well as histopathologic effects of reproductive organs.

Keywords: antidepressant, biochemical parameters, reproductive function, paroxetine

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Authors: Bilal Ahmad

Abstract:

Alzheimer’s disease (AD) is one of the most common neurodegenerative illnesses. However, how Gut-microbiota plays a role in the pathogenesis of AD is not well elucidated. The purpose of this literature review is to summarize and understand the current findings that may elucidate the gut microbiota's role in the development of AD. Methods: A literature review of all the relevant papers known to the author was conducted. Relevant articles, abstracts and research papers were collected from well-accepted web sources like PubMed, PMC, and Google Scholar. Results: Recent studies have shown that Gut-microbiota has an important role in the progression of AD via Gut-Microbiota-Brain Axis. The onset of AD supports the ‘Hygiene Hypothesis’, which shows that AD might begin in the Gut, causing dysbiosis, which interferes with the intestinal barrier by releasing pro-inflammatory cytokines and making its way up to the brain via the blood-brain barrier (BBB). Molecular mechanisms lipopolysaccharides and serotonin kynurenine (tryptophan) pathways have a direct association with inflammation, the immune system, neurodegeneration, and AD. Conclusion: The studies helped to analyze the molecular basis of AD, other neurological conditions like depression, autism, and Parkinson's disease and how they are linked to Gut-microbiota. Further, studies to explore the therapeutic effects of probiotics in AD and cognitive enhancement should be warranted to provide significant clinical and practical value.

Keywords: gut-microbiota, Alzheimer’s disease, second brain aging, lipopolysaccharides, short-chain fatty acids

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Authors: Ramin Mehdiabadi, Neda Menbari, Mohammad Nazir Menbari

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As a pressing public health concern, breast cancer stands as the predominant oncological diagnosis and principal cause of cancer-related mortality among women globally, accounting for 11.7% of new cancer incidences and 6.9% of cancer-related deaths. The annual figures indicate that approximately 230,480 women are diagnosed with breast cancer in the United States alone, with 39,520 succumbing to the disease. While developed economies have reported a deceleration in both incidence and mortality rates across various forms of cancer, including breast cancer, emerging and low-income economies manifest a contrary escalation, largely attributable to lifestyle-mediated risk factors such as tobacco usage, physical inactivity, and high caloric intake. Breast cancer is distinctly characterized by molecular heterogeneity, manifesting in specific subtypes delineated by biomarkers—Estrogen Receptors (ER), Progesterone Receptors (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). These subtypes, comprising Luminal A, Luminal B, HER2-enriched, triple-negative/basal-like, and normal-like, necessitate nuanced, subtype-specific therapeutic regimens, thereby challenging the applicability of generalized treatment protocols. Within this molecular complexity, the transcription factor Forkhead Box M1 (FoxM1) has garnered attention as a significant driver of cellular proliferation, tumorigenesis, metastatic progression, and treatment resistance in a spectrum of human malignancies, including breast cancer. Concurrently, microRNAs (miRs), specifically miR-216b-5p, have been identified as post-transcriptional gene expression regulators and potential tumor suppressors. The overarching objective of this academic investigation is to explicate the multifaceted interrelationship between FoxM1 and miR-216b-5p across the disparate molecular subtypes of breast cancer. Employing a methodologically rigorous, interdisciplinary research design that incorporates cutting-edge molecular biology techniques, sophisticated bioinformatics analytics, and exhaustive meta-analyses of extant clinical data, this scholarly endeavor aims to unveil novel biomarker-specific therapeutic pathways. By doing so, this research is positioned to make a seminal contribution to the advancement of personalized, efficacious, and minimally toxic treatment paradigms, thus profoundly impacting the global efforts to ameliorate the burden of breast cancer.

Keywords: breast cancer, fox m1, microRNAs, mir-216b-5p, gene expression

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Authors: Pinhas Dannon, Aviv Weinstein

Abstract:

Impulsivity is raising major interest clinically because it is associated with various clinical conditions such as delinquency, antisocial behavior, suicide attempts, aggression, and criminal activity. The evolutionary perspective argued that impulsivity relates to self-regulation and it has predicted that female individuals should have evolved a greater ability to inhibit pre-potent responses. There is supportive evidence showing that female individuals have better performance on cognitive tasks measuring impulsivity such as delay in gratification and delayed discounting mainly in childhood. During adolescence, brain imaging studies using diffusion tensor imaging on white matter architecture indicated contrary to the evolutionary perspective hypothesis, that young adolescent male individuals may be less vulnerable than age-matched female individuals to risk- and reward- related maladaptive behaviors. In adults, the results are mixed presumably owing to hormonal effects on neuro-biological mechanisms of reward. Consequently, female individuals were less impulsive than male individuals only during fertile stages of the menstrual cycle. Finally, there is evidence the serotonin (5-HT) system is more involved in the impulsivity of men than in that of women. Overall, there seem to be sex differences in impulsivity but these differences are more pronounced in childhood and they are later subject to maturational and hormonal changes during adolescence and adulthood and their effects on the brain, cognition, and behavior.

Keywords: impulse control, male population, female population, gender differences, reward, neurocognitive tests

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Authors: H. Yousefnia, A. Golabi Dezfuli, S. Zolghadri, M. Hosntalab

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Peptide receptor radionuclide therapy is nowadays used for the treatment of various abnormalities with somatostatin receptors. In this study, 166Ho-DOTATOC was prepared and the best conditions for its radiolabeling was obtained. For this purpose, a certain of DOTATOC was added to a vial containing 166Ho. various experiments by varying ligand concentration, pH, temperature and time were performed to determine the best conditions. Radiochemical purity of the complex was assessed by instant thin layer chromatography method utilizing 0.9% NaCl as the mobile phase. 166Ho-DOTATOC was prepared with radiochemical purity of higher than 95% at the optimized condition (pH=4, temperature: 95° C, time:30 min). In 0.9% NaCl, free Ho cation was developed at Rf of 0.8 while the complex was remained at the front of the paper.

Keywords: Ho-166, neuroendocrine, octreotide, quality control

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Authors: Mahsa Jalili, Essa Ehsan Khan, Signe Dille Lovmo, Augustine Akruwe, Egil Lien, Rolf Erik Olsen, Trygve Sigholt, Atle Magnus Bones

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Data from the Norwegian Directorate of Fisheries reported that >1.2 million tons of Atlantic salmon were produced in Norway aquaculture industry in 2016. Peroxisome proliferator-activated receptors (PPARs) are one of the key transcription factor families that respond to nutritional ligands. Recent studies have shown the connection between PPARs with lipid and carbohydrate metabolism in aquaculture. To our knowledge, there is no published data about the effects of krill meal, soybean meal, Bactocell ® and butyrate feedings compared to control group on PPARs gene and protein expressions in Atlantic salmon. Fish, 1year +postsmolt, average weight 250 gram were cultured for 12 weeks after acclimatization by control commercial feeding in 2 weeks after hatchery. Water oxygen rate, salinity, and temperature were monitored every second day. At the end of the trial, fish were taken from tanks randomly, and four replicates per group were collected and stored in -80 freezers until analysis. Total RNA extracted from posterior part of dorsal fin muscle tissues and Nanodrop and Bioanalyzer was used to check the quality of RNA. Gene expression of PPAR α, β and γ were determined by RT-PCR. The expression of genes of interest was measured relative to control group after normalization to three reference genes. Total protein concentration was calculated by Bradford method, and protein expression was determined with primary PPARγ antibody by western blot. All data were analyzed by ANOVA followed by Benjamini-Hochberg and Bonferroni tests. Probability values <0.05 considered significant. Bactocell® and butyrate groups showed significantly lower PPARα expression. PPARβ and γ were not significantly different among groups. PPARγ mRNA expression was approximately consistent with protein expression pattern, except than butyrate group showed lower mRNA level. The order of PPARγ expression was Bactocell® > soy meal > butyrate > krill meal > control respectively. PPARβ gene expression decreased more in soy meal > butyrate > krill meal > Bactocell® > control groups respectively. In conclusion, the increased expression of PPARγ and α is proposed to represent a reduction tendency of lipid storage in fish fed by Bactocell®, butyrate, soy and krill meal.

Keywords: aquaculture, blotting western, gene expression, krill protein extract, prebiotics, probiotics, Salmo salar

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Authors: Mihai Palade, Gina Cecilia Pistol, Mariana Stancu, Veronica Chedea, Ionelia Taranu

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Nutrition is an important determinant of general health status, with especially focus on prevention and/or attenuation of the inflammatory-associated pathologies. People with chronic kidney disease can experience chronic inflammation that can lead to cardiovascular disease and even an increased rate of death. There are important links between chronic kidney diseases, inflammation and nutritional strategies that may prevent or protect against undesirable inflammation and oxidative stress. The grape by-products either seeds or pomace are rich in polyphenols which may be beneficial in prevention of inflammatory, antioxidant and antimicrobial processes. As a model for studying the impact of grape seeds on renal inflammation and oxidative stress, we used in this study weaned piglets. After a feeding trial of 30 days with a control diet and an experimental diet containing 5% grape seed (GS), kidney samples were collected. In renal tissues were determined the expression and activity of important markers of immune respose and oxidative stress: pro-inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6, IL-8, IFN-gamma), anti-inflammatory cytokines (IL-4, IL-10), anti-oxidant enzymes (catalase CAT, superoxide dismutase SOD, glutathione peroxidise GPx) and important mediators belonging to nuclear receptors (NF-kB1, Nrf-2 and PPAR-gamma). Gene expression was evaluated by qPCR, whereas protein concentration was determined using proteomic techniques (ELISA). The activity of anti-oxidant enzymes was determined using specific kits. Our results showed that GS enriched in polyphenols does not have effect on TNF-alpha, IL-6 and IL-1 beta gene expression and protein concentration in kidney. By contrast, the gene expression and protein level of IL-8 and IFN-gamma were decreased in GS kidney. Anti-inflammatory cytokines IL-4 and IL-10 gene levels were increased in kidneys collected from GS piglets in comparison with controls, with no modification of protein levels between the two groups. The activities of anti-oxidant enzymes CAT and GPx were increased in kidney by GS, whereas SOD activity was unmodified in comparison with control samples. Also, the GS diet was associated with no modulation of mRNAs for nuclear receptors NF-kB1, Nrf-2 and PPAR-gamma gene expressions in kidneys. In conclusion, our results demonstrated that GS enriched in bioactive compounds such polyphenols could modulate inflammation and oxidative stress markers in kidney tissues. Further studies are necessary to elucidate the mechanism of action of GS compounds in case kidney inflammation associated with oxidative stress, and signalling molecules involved in these mechanisms.

Keywords: animal model, kidney inflammation, oxidative stress, grape seed

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Authors: Fatih Özogul, Nurten Toy, Yesim Özogul

Abstract:

The influences of cell-free solutions (CFSs) of lactic acid bacteria (LAB) on cadaverine and other biogenic amine production by Listeria monocytogenes and Staphylococcus aureus were investigated in lysine decarboxylase broth (LDB) using HPLC. Cell-free solutions were prepared from Lactococcus lactis subsp. lactis, Leuconostoc mesenteroides subsp. cremoris, Pediococcus acidophilus and Streptococcus thermophiles. Two different concentrations that were 50% and 25% CFS and the control without CFSs were prepared. Significant variations on biogenic amine production were observed in the presence of L. monocytogenes and S. aureus (P<0.05). The role of CFS on biogenic amine production by foodborne pathogens varied depending on strains and specific amine. Cadaverine formation in control by L. monocytogenes and S. aureus were 500.9 and 948.1 mg/L, respectively while the CFSs of LAB induced 4-fold lower cadaverine production by L. monocytogenes and 7-fold lower cadaverine production by S. aureus. CFSs resulted in strong decreases in cadaverine and putrescine production by L. monocytogenes and S. aureus, although remarkable increases were observed for histamine, spermidine, spermine, serotonin, dopamine, tyramine, and agmatine, in the presence of LAB in lysine decarboxylase broth.

Keywords: cell-free solution, lactic acid bacteria, cadaverine, food borne-pathogen

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Authors: Bouchaïb Gazzaz, Hamid El Amri, Hind Dehbi, Abderraouf Hilali

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Medical cannabis has been cultivated and used in many countries around the world. The story of the use of cannabis as a therapeutic agent is difficult to trace, in particular, because the laws regulating its production, distribution, possession, and consumption are relatively recent. Nowadays, in countries where it is authorized, medical cannabis is used in a very wide variety of illnesses and pathologies, particularly in cancer cures. Presently, cannabinoid receptor agonists (like nabilone and dronabinol) are used for reducing chemotherapy induced vomiting. This review aims to discuss a recent finding on the use of therapeutic cannabis in patients with cancer. First, this work addresses the progress made in the use of cannabinoids as therapeutic agent and their application in the treatment of different types of cancer. Secondly, a detailed analysis of the pharmacogenetic aspect of cannabis will be discussed.

Keywords: cannabinoids, endocannabinoids system, cancer treatment, cannabinoid receptors, genetic polymorphism, pharmacogenomics

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Authors: Amir Bastani

Abstract:

The result of the research in the field of human behavioural genetics demonstrates a genetic contribution of behavioural differences in aggression, violence, drug and substance abuse, antisocial personality disorder and other related traits. As the field of human behavioural genetics progresses and achieves credibility, the criminal accused continue to use its types of evidence into the criminal law. One of the most important genetic factors which controls certain neurotransmitters like dopamine and serotonin is the Monoamine Oxidase Acid A (MAOA) gene, known as the 'warrior gene'. The high-profile study by Caspi and colleagues in 2002 showed that the combination between one type of variation of the MAOA gene and childhood maltreatment noticeably predisposes a person to antisocial behaviour. Moreover, further scientific research shows that individuals with the MAOA gene have to some degree difficulties in controlling their impulses. Based on the evidence of MAOA, some criminal accused claimed difficulties in self-control. In the first case – the famous case of Mobley – the court rejected the MAOA evidence on the ground of the lack of scientific support. In contrast, in other cases after the Mobley trial, courts accepted the evidence of MAOA. In this paper, the issue of lack of impulse control produced by the MAOA gene and cases which relied on the MAOA evidence and successfully being accepted will be reviewed in detail. Finally, the anticipation of the paper for the future use of the MAOA evidence in criminal cases will be presented.

Keywords: genetic defence, criminal responsibility, MAOA, self-control

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Authors: Eric Chabrol, Sidonia B.G. Eckle, Renate de Boer, James McCluskey, Jamie Rossjohn, Mirjam H.M. Heemskerk, Stephanie Gras

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αβ and γδ T-cells are disparate T-cell lineages that, via their use of either αβ or γδ T-cell antigen receptors (TCRs) respectively, can respond to distinct antigens. Here we characterise a new population of human T-cells, term δβ T-cells, that express TCRs comprising a TCR-δ variable gene fused to a Joining-α/Constant-α domain, paired with an array of TCR-β chains. We characterised the cellular, functional, biophysical and structural characteristic feature of this new T-cells population that reveal some new insight into TCR diversity. We provide molecular bases of how δβ T-cells can recognise viral peptide presented by Human Leukocyte Antigen (HLA) molecule. Our findings highlight how components from αβ and γδTCR gene loci can recombine to confer antigen specificity thus expanding our understanding of T-cell biology and TCR diversity.

Keywords: new delta-beta TCR, HLA, viral peptide, structural immunology

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Authors: John G. Skelly, Peter K. Dearden, Thomas W. R. Harrop, Sarah N. Inwood, Joseph Guhlin

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The Argentine stem weevil (ASW; L. bonariensis) is an economically important pasture pest in New Zealand, which causes about $200 million of damage per annum. Microctonus hyperodae (Mh), a parasite of the ASW in its natural range in South America, was introduced into New Zealand to curb the pasture damage caused by the ASW. Mh is an endoparasitic wasp that lays its eggs in the ASW halting its reproduction. Mh was initially successful at preventing ASW proliferation and reducing pasture damage. The effectiveness of Mh has since declined due to decreased parasitism rates and has resulted in increased pasture damage. Although the mechanism through which ASW has developed resistance to Mh has not been discovered, it has been proposed to be due to the different reproductive modes used by Mh and the ASW in New Zealand. The ASW reproduces sexually, whereas Mh reproduces asexually, which has been hypothesised to have allowed the ASW to ‘out evolve’ Mh. Other species within the Microctonus genus reproduce both sexually and asexually. Strains of Microctonus aethiopoides (Ma), a species closely related to Mh, reproduce either by sexual or asexual reproduction. Comparing the genomes of sexual and asexual Microctonus may allow for the identification of the mechanism of asexual reproduction and other characteristics that may improve Mh as a biocontrol agent. The genomes of Mh and three strains of Ma, two of which reproduce sexually and one reproduces asexually, have been sequenced and annotated. The French (MaFR) and Moroccan (MaMO) reproduce sexually, whereas the Irish strain (MaIR) reproduces asexually. Like Mh, The Ma strains are also used as biocontrol agents, but for different weevil species. The genomes of Mh and MaIR were subsequently upgraded using Hi-C, resulting in a set of high quality, highly contiguous genomes. A subset of the genes involved in mitosis and meiosis, which have been identified though the use of Hidden Markov Models generated from genes involved in these processes in other Hymenoptera, have been catalogued in Mh and the strains of Ma. Meiosis and mitosis genes were broadly conserved in both sexual and asexual Microctonus species. This implies that either the asexual species have retained a subset of the molecular components required for sexual reproduction or that the molecular mechanisms of mitosis and meiosis are different or differently regulated in Microctonus to other insect species in which these mechanisms are more broadly characterised. Bioinformatic analysis of the chemoreceptor compliment in Microctonus has revealed some variation in the number of olfactory receptors, which may be related to host preference. Phylogenetic analysis of olfactory receptors highlights variation, which may be able to explain different host range preferences in the Microctonus. Hi-C clustering implies that Mh has 12 chromosomes, and MaIR has 8. Hence there may be variation in gene regulation between species. Genome alignment of Mh and MaIR implies that there may be large scale genome structural variation. Greater insight into the genetics of these agriculturally important group of parasitic wasps may be beneficial in restoring or maintaining their biocontrol efficacy.

Keywords: argentine stem weevil, asexual, genomics, Microctonus hyperodae

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Authors: Andreas Aceranti, Sergio Romanò, Simonetta Vernocchi, Silvia Arnaboldi, Emilio Mazza

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As a result of the Sars-Cov2 pandemic, the incidence of thymism disorders has significantly increased and, often, patients are reluctant to want to take drugs aimed at stabilizing mood. In order to provide an alternative approach to drug therapies, we have prepared a study in order to evaluate the possibility of improving the quality of life of these subjects through osteopathic treatment. Patients were divided into visceral and fascial manual treatment with the aim of increasing serotonin levels and stimulating the vagus nerve through validated techniques. The results were evaluated through the administration of targeted questionnaires in order to assess quality of life, mood, sleep and intestinal functioning. At a first endpoint we found, in patients undergoing fascial treatment, an increase in quality of life and sleep: in fact, they report a decrease in the number of nocturnal awakenings; a reduction in falling asleep times and greater rest upon waking. In contrast, patients undergoing visceral treatment, as well as those included in the control group, did not show significant improvements. Patients in the fascial group have, in fact, reported an improvement in thymism and subjective quality of life with a generalized improvement in function. Although the study is still ongoing, based on the results of the first endpoint we can hypothesize that fascial stimulation of the vagus nerve with manual and osteopathic techniques may be a valid alternative to pharmacological treatments in mood and sleep disorders.

Keywords: ostheopathy, insomnia, noctural awakening, thymism

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Authors: Gursimran Jandu, Melissa Nelson, Mia Ingram, Hana Jalal

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There is a significant overlap between autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD), with up to 90% of young people diagnosed with ASD having this co-morbidity. Distinguishing between the symptoms of the two leads to issues with accurate treatment, yet this is paramount in benefiting the young person. There are two distinct methods of treatment, psychological or pharmacological, with clinicians tending to choose one or the other, potentially due to the lack of research available. This report reviews the efficacy of psychological and pharmacological treatments for young people diagnosed with ASD and co-morbid OCD. A literature review was performed on papers from the last fifteen years including ‘ASD’, ‘OCD’ and individuals under the age of 18. Eleven papers were selected as relevant. The report looks at the comparison between more traditional methods, such as selective-serotonin-reuptake-inhibitors (SSRI) and Cognitive behaviour therapy (CBT), and newer therapies, such as modified or intensive ASD focused psychotherapies, and the use of other medication classes. On reviewing the data, it was identified that there was a distinct lack of information on this important topic. The most widely used treatment was medication such as Fluoxetine, an SSRI, which rarely showed improvement in symptoms or outcomes. This is in contrast to modified forms of CBT which often reduces symptoms or even results in OCD remission. With increased research into non-traditional management of these co-morbid conditions, it is clear there is scope that modified CBT may become the future treatment of choice for OCD in young people with ASD.

Keywords: autism spectrum disorder, intensive or adapted cognitive behavioural therapy, obsessive compulsive disorder, pharmacological management

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Authors: Mazo Kone, Rachida Salah, Harir Noria

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Background and objectives: c-Cbl and Cbl-b are two members of the Cbl family proteins, with a crucial role of downregulation of tyrosine kinase receptors. They act as E3 ubiquitin ligases and are multivalent adaptor proteins, making them important in maintaining homeostasis in the body. This study investigated the expression level in thymus and testis in normal conditions. Methods: The expression level was assessed by immunochemistry of tissue microarrays of normal thymus and testis biopsies. Results: Cbl-b and c-Cbl proteins were found to be highly expressed in normal testis and thymus, indicated as yellowish brown granules in the cytomembrane and cytoplasm compared to controls. The c-Cbl appears to be more highly expressed than the Cbl-b in the thymus, while c-Cbl appears slightly stronger than Cbl-b in the testis. The thymus was found with a higher grade compared to the testis. Conclusion: In this work we concluded, that in normal condition, thymus tissue expresses more Cbl family proteins(c-Cbl and Cbl-b) than the testis tissue in humans.

Keywords: Human C-Cbl proteins, Human Cbl-b protein, Testis, Thymus

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Authors: Melissa Nelson, Simran Jandu, Hana Jalal, Mia Ingram, Chrysi Stefanidou

Abstract:

There is a significant overlap between autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD), with up to 90% of young people diagnosed with ASD having this co-morbidity. Distinguishing between the symptoms of the two leads to issues with accurate treatment, yet this is paramount in benefitting the young person. There are two distinct methods of treatment, psychological or pharmacological, with clinicians tending to choose one or the other, potentially due to the lack of research available. This report reviews the efficacy of psychological and pharmacological treatments for young people diagnosed with ASD and co-morbid OCD. A literature review was performed on papers from the last fifteen years, including “ASD,” “OCD,” and individuals under the age of 18. Eleven papers were selected as relevant. The report looks at the comparison between more traditional methods, such as selective serotonin reuptake inhibitors (SSRI) and cognitive behavior therapy (CBT), and newer therapies, such as modified or intensive ASD-focused psychotherapies and the use of other medication classes. On reviewing the data, it was identified that there was a distinct lack of information on this important topic. The most widely used treatment was medication such as Fluoxetine, an SSRI, which rarely showed an improvement in symptoms or outcomes. This is in contrast to modified forms of CBT, which often reduces symptoms or even results in OCD remission. With increased research into the non-traditional management of these co-morbid conditions, it is clear there is scope that modified CBT may become the future treatment of choice for OCD in young people with ASD.

Keywords: autism spectrum disorder, intensive or adapted cognitive behavioral therapy, obsessive compulsive disorder, pharmacological management

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Authors: Narin Salehiyan, Ramin Ghasemi Shayan

Abstract:

In order to investigate coronavirus RNA replication, transcription, recombination, protein processing and transport, virion assembly, the identification of coronavirus-specific cell receptors, and polymerase processing, the manipulation of coronavirus clones and complementary DNAs (cDNAs) of defective-interfering (DI) RNAs is the subject of this chapter. The idea of the Covid genome is nonsegmented, single-abandoned, and positive-sense RNA. When compared to other RNA viruses, its size is significantly greater, ranging from 27 to 32 kb. The quality encoding the enormous surface glycoprotein depends on 4.4 kb, encoding a forcing trimeric, profoundly glycosylated protein. This takes off exactly 20 nm over the virion envelope, giving the infection the appearance-with a little creative mind of a crown or coronet. Covid research has added to the comprehension of numerous parts of atomic science as a general rule, like the component of RNA union, translational control, and protein transport and handling. It stays a fortune equipped for creating startling experiences.

Keywords: covid-19, corona, virus, genome, genetic

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Authors: Nur Hidayah Kaz Abdul Aziz, Norhalida Hashim, Zurina Hassan

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Peripartum period is a time where women are vulnerable to depression, and stress may further increase the risk of its occurrence. Use of selective serotonin reuptake inhibitors (SSRI) in the treatment of postpartum depression is a common practice. Comparison of antidepressant treatment, however, is rarely studied between gestated and nulliparous animals exposed to stress. This study was aimed to investigate the effect of parity and stress, as well as fluoxetine (an SSRI) treatment after stress exposure on the behavior of rats. Gestating and nulliparous Sprague Dawley rats were either subjected to chronic stressors or left undisturbed throughout the gestation period. After parturition, all stressors were stopped and some of the stressed rats were treated with fluoxetine (10mg/kg). Hence, the final groups formed were: 1. Non-stressed nulliparous rats, 2. Non-stressed dams, 3. Stressed nulliparous rats, 4. Stressed dams, 5. Fluoxetine-treated stressed nulliparous rats, and 6. Fluoxetine-treated stressed dams. Rats were tested in open field test (OFT), novel object recognition test (NOR) and forced swim test (FST) after weaning of pups. Gestational stress significantly reduced the locomotor activity of rats in OFT (p<0.05), while fluoxetine significantly increased the activity in nulliparous rats (p<0.001) but not the dams. While no differences were observed in NOR, stress and parity inhibited the rats from performing swimming behavior in FST. However, climbing and immobile behaviors in FST were found to have no significant differences, although there is a tendency of effect of treatment for immobility parameter (p=0.06) where fluoxetine-treated stressed dams were being the least immobile. In conclusion, the effects of parity and stress, as well as fluoxetine treatment, depended on the type of behavioral test performed.

Keywords: stress, parity, SSRI, behavioral tests

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Authors: Fei Xu, Guofan Zhang, Xiao Liu

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Many major marine invertebrate phyla are characterized by indirect development. These animals transit from planktonic larvae to benthic adults via settlement and metamorphosis, which has many advantages for organisms to adapt marine environment. Studying the biological process of metamorphosis is thus a key to understand the origin and evolution of indirect development. Although the mechanism of metamorphosis has been largely studied on their relationships with the marine environment, microorganisms, as well as the neurohormones, little is known on the gene regulation network (GRN) during metamorphosis. We treated competent oyster pediveligers with epinephrine, which was known to be able to effectively induce oyster metamorphosis, and analyzed the dynamics of gene and proteins with transcriptomics and proteomics methods. The result indicated significant upregulation of protein synthesis system, as well as some transcription factors including Homeobox, basic helix-loop-helix, and nuclear receptors. The result suggested the GRN complexity of the transition stage during oyster metamorphosis.

Keywords: indirect development, gene regulation network, protein synthesis, transcription factors

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Authors: Federico Cevoli

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Purinergic P2X7 receptors (P2X7R) are ligand-gated non-selective cation channels involved in several physiological and pathological processes. They are particularly promising pharmacological targets as they are present in an increasing number of different cells types. P2X7R activation is triggered following elevated concentrations of extracellular ATP, similarly to those observed in tissues injury, chronic inflammation and T-cell activation, as well as in the scrambling of phospholipids leading to membrane blebbing and apoptosis. Another hallmark of P2X7 is cell permeabilization, commonly known as “macropore” formation allowing the passage of nanometer-sized molecules up to 900Da. Recently, full-length P2X7 Cryo-EM structures revealed unique functional sites, including two cytoplasmic domains - the cytoplasmic "anchor" and "ballast". To date, the molecular units/complex by which P2X7R exerts its pathophysiological functions are unknown. Using custom-made cell-penetrating HIV-1 TAT peptides, we show for the first-time potential implications of P2X7 cytoplasmic anchor in the regulation of caspase3/7 activation as well as TNFα regulation.

Keywords: P2X7R, immunology, TAT-peptide, cell death

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Authors: Muhammad Badruzzaman, Alif Hasan, Md. Shahjahan

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Propiconazole is a triazole fungicide extensively used in agriculture which can harm to non-target organisms in aquatic environment through runoff. Chronic exposure to environmental pesticides turn to behavioral impairment in vertebrates including teleosts. However, the potential effect of this fungicide on neurobehavioral impairment and release from it in vertebrates has not been fully explored. In this work, we examined the role of melatonin to rescue fungicide induced neurobehavioral and reproductive alternation and its connection with changes in dopaminergic activity in the brain of Mystus cavasius. After fish were exposed to water containing propiconazole at 0, 0.1, 5, and 250 µg/L for 3 days, significant increases of DA, 3,4-dihydroxyphenylacetic acid (DOPAC; a DA metabolite), and their ratio (DOPAC/DA) were observed in whole brain at 250 µg/L concentration. When fish were treated with propiconazole at 250 µg/L for 3 days, there was a significant elevation of DA, DOPAC and DOPAC/DA in diencephalon and pituitary, and only DA in the telencephalon, compared with control fish. Besides, it induced a reduction in extracellular serotonin and had an anxiolytic-like effect, supported by a decrease in cortisol production. Increased locomotor activity, anxiety and aggressiveness, decreased gonadosomatic index with few vitellogenic oocytes in ovaries after propiconazole treatment. When fish were treated with melatonin, D1 (SCH-23390) or D2 (Haloperidol) dopamine receptor antagonists and combined of melatonin and D1/D2 receptor antagonist and was observed melatonin + D2 receptor antagonist rescued fungicide induced all behavioral changes in fish. These results indicate that propiconazole increases locomotor activity, anxiety and aggressiveness and decreases reproductive activity, which was rescued by combined treatment of melatonin and dopamine receptor antagonist.

Keywords: behavior, catfish, dopamine, fungicide, melatonin

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Authors: Srie Rezeki Nur Endah, Richa Mardianingrum

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Cancer is one of the most feared diseases and is considered the leading cause of death worldwide. Generally, cancer drugs are synthetic drugs with relatively more expensive prices and have harmful side effects, so many people turn to traditional medicine, for example by utilizing herbal medicine. Erythrina poeppigiana is one of the plants that can be used as a medicinal plant containing 10,11-dihidroerisodin compounds that are useful anticancer etnofarmakologi. The purpose of this study was to identify the target of 10,11 dihydroerisodin receptor compound as in silico anticancer candidate. The pure isolate was tested physicochemically by MS (Mass Spectrometry), UV-Vis (Ultraviolet – Visible), IR (Infra Red), 13C-NMR (Carbon-13 Nuclear Magnetic Resonance), 1H-NMR (Hydrogen-1 Nuclear Magnetic Resonance), to obtain the structure of 10,11-dihydroerisodin alkaloid compound then identified to target receptors in silico. From the results of the study, it was found that 10,11-dihydroerisodin compound can work on the Serine / threonine-protein kinase Chk1 receptor that serves as an anti-cancer candidate.

Keywords: anti-cancer, Erythrina poeppigiana, target receptor, 10, 11- dihidroerisodin

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Authors: Fatih Özogul, Esmeray Kuley Boga, Ferhat Kuley, Yesim Özogul

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The impact of diethyl ether extract of spices (sumac, cumin, black pepper and red pepper) on growth of Staphylococcus aureus, Salmonella Paratyphi A, Klebsiella pneumoniae, Enterococcus faecalis, Camplylobacter jejuni, Aeromonas hydrophila, Pseudomonas aeruginosa and Yersinia enterocolitica and their biogenic amine production were investigated in tyrosine decarboxylase broth. Sumac extract generally had the highest activity to inhibit bacterial growth compared to other extracts, although antimicrobial effect of extracts used varied depending on bacterial strains. Sumac extract resulted in 3.34 and 2.54 log reduction for Y. enterocolitica and Camp. jejuni growth, whilst red pepper extract induced 0.65, 0.41 and 0.34 log reduction for growth of Y. enterocolitica, S. Paratyphi A and Staph. aureus, respectively. Spice extracts significantly inhibited ammonia production by bacteria (P < 0.05). Eleven and nine fold reduction on ammonia production by S. Paratyphi A and Staph. aureus were observed in the presence of sumac extract. Dopamine, agmatine, tyramine, serotonin and TMA were main amines produced by bacteria. Tyramine production by food-borne-pathogens was more than 10 mg/L, whereas histamine accumulated below 52 mg/L. The effect of spice extracts on biogenic amine production varied depending on amino acid decarboxylase broth, spice type, bacterial strains and specific amine, although cumin extract generally increased biogenic amine production by bacteria.

Keywords: antimicrobials, biogenic amines, food-borne pathogens, spice extracts

Procedia PDF Downloads 312

Authors: Marawan Abd Elbaset Mohamed, Hanan A. Ogaly, Rehab F. Abdel-Rahman, Ahmed-Farid O.A., Marwa S. Khattab, Reham M. Abd-Elsalam

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Liver fibrosis is a severe worldwide health concern due to various chronic liver disorders. Hepatic encephalopathy (HE) is one of its most common complications affecting liver and brain cognitive function. Beta-Carotene (B-Car) is an organic, strongly colored red-orange pigment abundant in fungi, plants, and fruits. The study attempted to know B-Car neuroprotective potential against thioacetamide (TAA)-induced neurotoxicity and cognitive decline in HE in rats. Hepatic encephalopathy was induced by TAA (100 mg/kg, i.p.) three times per week for two weeks. B-Car was given orally (10 or 20 mg/kg) daily for two weeks after TAA injections. Organ body weight ratio, Serum transaminase activities, liver’s antioxidant parameters, ammonia, and liver histopathology were assessed. Also, the brain’s mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB), antioxidant parameters, adenosine triphosphate (ATP), adenosine monophosphate (AMP), norepinephrine (NE), dopamine (DA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) cAMP response element-binding protein (CREB) expression and B-cell lymphoma 2 (Bcl-2) expression were measured. The brain’s cognitive functions (Spontaneous locomotor activity, Rotarod performance test, Object recognition test) were assessed. B-Car prevented alteration of the brain’s cognitive function in a dose-dependent manner. The histopathological outcomes supported these biochemical evidences. Based on these results, it could be established that B-Car could be assigned to treat the brain’s neurotoxicity consequences of HE via downregualtion of MAPK/NF-κB signaling pathways.

Keywords: beta-carotene, liver injury, MAPK, NF-κB, rat, thioacetamide

Procedia PDF Downloads 154

Authors: Bianca Peterson, Tomasz J. Sańko, Carlos C. Bezuidenhout, Johnnie Van Den Berg

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Busseola fusca (Fuller) (Lepidoptera: Noctuidae), the maize stem borer, is a major pest in sub-Saharan Africa. It causes economic damage to maize and sorghum crops and has evolved non-recessive resistance to genetically modified (GM) maize expressing the Cry1Ab insecticidal toxin. Since B. fusca is a non-model organism, very little genomic information is publicly available, and is limited to some cytochrome c oxidase I, cytochrome b, and microsatellite data. The biology of B. fusca is well-described, but still poorly understood. This, in combination with its larval-specific behavior, may pose problems for limiting the spread of current resistant B. fusca populations or preventing resistance evolution in other susceptible populations. As part of on-going research into resistance evolution, B. fusca larvae were collected from Bt and non-Bt maize in South Africa, followed by RNA isolation (15 specimens) and sequencing on the Illumina HiSeq 2500 platform. Quality of reads was assessed with FastQC, after which Trimmomatic was used to trim adapters and remove low quality, short reads. Trinity was used for the de novo assembly, whereas TransRate was used for assembly quality assessment. Transcript identification employed BLAST (BLASTn, BLASTp, and tBLASTx comparisons), for which two libraries (nucleotide and protein) were created from 3.27 million lepidopteran sequences. Several transcripts that have previously been implicated in Cry toxin resistance was identified for B. fusca. These included aminopeptidase N, cadherin, alkaline phosphatase, ATP-binding cassette transporter proteins, and mitogen-activated protein kinase. MEGA7 was used to align these transcripts to reference sequences from Lepidoptera to detect mutations that might potentially be contributing to Cry toxin resistance in this pest. RSEM and Bioconductor were used to perform differential gene expression analysis on groups of B. fusca larvae challenged and unchallenged with the Cry1Ab toxin. Pairwise expression comparisons of transcripts that were at least 16-fold expressed at a false-discovery corrected statistical significance (p) ≤ 0.001 were extracted and visualized in a hierarchically clustered heatmap using R. A total of 329,194 transcripts with an N50 of 1,019 bp were generated from the over 167.5 million high-quality paired-end reads. Furthermore, 110 transcripts were over 10 kbp long, of which the largest one was 29,395 bp. BLAST comparisons resulted in identification of 157,099 (47.72%) transcripts, among which only 3,718 (2.37%) were identified as Cry toxin receptors from lepidopteran insects. According to transcript expression profiles, transcripts were grouped into three subclusters according to the similarity of their expression patterns. Several immune-related transcripts (pathogen recognition receptors, antimicrobial peptides, and inhibitors) were up-regulated in the larvae feeding on Bt maize, indicating an enhanced immune status in response to toxin exposure. Above all, extremely up-regulated arylphorin genes suggest that enhanced epithelial healing is one of the resistance mechanisms employed by B. fusca larvae against the Cry1Ab toxin. This study is the first to provide a resource base and some insights into a potential mechanism of Cry1Ab toxin resistance in B. fusca. Transcriptomic data generated in this study allows identification of genes that can be targeted by biotechnological improvements of GM crops.

Keywords: epithelial healing, Lepidoptera, resistance, transcriptome

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Authors: M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani, S. Zolghadri, S. Kakaei

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Despite the appropriate characteristics of ¹⁷⁷Lu and DOTATOC, to our best knowledge, the therapeutic benefit of ¹⁷⁷Lu-DOTATOC complex in breast cancer has not been reported until now. In this study, biodistribution of ¹⁷⁷Lu-DOTA-TOC in mouse tumor model for evaluation of possible utilization of this complex in breast cancer treatment was investigated.¹⁷⁷Lu was prepared with the specific activity of 2.6-3 GBq.mg^-1 and radionuclidic purity higher than 99%. The radiolabeled complex was prepared in the optimized conditions with the radiochemical purity higher than 99%. The final solution was injected to the BALB/c mice with adenocarcinoma breast cancer. The biodistribution results showed major accumulation in the kidneys as the major excretion route and the somatostatin receptor-positive tissues such as pancreas compared with the other tissues. Also, significant uptake was observed in tumor even in longer time after injection. According to the results obtained in this research study, somatostatin receptors expressed in breast cancers can be targeted with DOTATOC analogues especially with ¹⁷⁷Lu-DOTATOC as an ideal therapeutic agent.

Keywords: ¹⁷⁷Lu, adenocarcinoma breast cancer, DOTATOC, BALB/c mice

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Authors: Rashi Rajput, Manisha Singh

Abstract:

Escitalopram oxalate (ETP), an FDA approved antidepressant drug from the category of SSRI (selective serotonin reuptake inhibitor) and is used in treatment of general anxiety disorder (GAD), major depressive disorder (MDD).When taken orally, it is metabolized to S-demethylcitalopram (S-DCT) and S-didemethylcitalopram (S-DDCT) in the liver with the help of enzymes CYP2C19, CYP3A4 and CYP2D6. Hence, causing side effects such as dizziness, fast or irregular heartbeat, headache, nausea etc. Therefore, targeted and sustained drug delivery will be a helpful tool for increasing its efficacy and reducing side effects. The present study is designed for formulating mucoadhesive nanoparticle formulation for the same Escitalopram loaded polymeric nanoparticles were prepared by ionic gelation method and characterization of the optimised formulation was done by zeta average particle size (93.63nm), zeta potential (-1.89mV), TEM (range of 60nm to 115nm) analysis also confirms nanometric size range of the drug loaded nanoparticles along with polydispersibility index of 0.117. In this research, we have studied the in vitro drug release profile for ETP nanoparticles, through a semi permeable dialysis membrane. The three important characteristics affecting the drug release behaviour were – particle size, ionic strength and morphology of the optimised nanoparticles. The data showed that on increasing the particle size of the drug loaded nanoparticles, the initial burst was reduced which was comparatively higher in drug. Whereas, the formulation with 1mg/ml chitosan in 1.5mg/ml tripolyphosphate solution showed steady release over the entire period of drug release. Then this data was further validated through mathematical modelling to establish the mechanism of drug release kinetics, which showed a typical linear diffusion profile in optimised ETP loaded nanoparticles.

Keywords: ionic gelation, mucoadhesive nanoparticle, semi-permeable dialysis membrane, zeta potential

Procedia PDF Downloads 294

Authors: Mehdi Sheikhi, Marjan Nassiri-Asl, Esmail Abbasi, Mahsa Shafiee

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Various synthetic derivatives of natural flavonoids are known to have neuroactive properties. The present study aimed to investigate the effects of vitexin (5, 7, 4-trihydroxyflavone-8-glucoside), a flavonoid found in such plants as tartary buckwheat sprouts, wheat leaves phenolome, Mimosa pudica Linn and Passiflora spp, on scopolamine-induced memory impairment in rats. To achieve this goal, we assessed the effects of vitexin on memory retrieval in the presence or absence of scopolamine using a step-through passive avoidance trial. In the first part of the study, vitexin (25, 50, and 100 μM) was administered intracerebroventricularly (i.c.v.) before acquisition trials. In the second part, vitexin, at the same doses, was administered before scopolamine (10 μg, i.c.v.) and before the acquisition trials. During retention tests, vitexin (100 μM) in the absence of scopolamine significantly increased the stepthrough latencies compared to scopolamine. In addition, vitexin (100 μM) significantly reversed the shorter step-through latencies induced by scopolamine (P < 0.05). These results indicate that vitexin has a potential role in enhancing memory retrieval. A possible mechanism is modulation of cholinergic receptors; however, other mechanisms may be involved in its effects in acute exposure.

Keywords: flavonoid, memory retrieval, passive avoidance, scopolamine, vitexin

Procedia PDF Downloads 352