71 research outputs found
Elevating metaverse virtual reality experiences through network-integrated neuro-fuzzy emotion recognition and adaptive content generation algorithms
Interactions between individuals and digital material have completely changed with the advent of the Metaverse. Due to this, there is an immediate need to construct cutting-edge technology that can recognize the emotions of users and continuously provide material that is relevant to their psychological states, improving their overall experience. An inventive method that combines natural language processing adaptive content generation algorithms and neuro-fuzzy-based support vector machines natural language processing (SVM-NLP) is proposed by researchers to meet this demand. With this merging, the Metaverse will be able to offer highly tailored and engaging experiences. Initially, a neuro-fuzzy algorithm was developed to identify people's emotional moods from their physiological reactions and other biometric information. Fuzzy Logic and Support Vector Machine work together to manage the inherent ambiguity and unpredictability, which results in a more exact and accurate categorization of emotions. A key component of the ACGA is NLP technology, which uses real-time emotional data to dynamically modify and personalize characters, stories, and interactive features in the Metaverse. The novelty of the proposed approach lies in the innovative integration of neuro-fuzzy-based SVM-NLP algorithms to accurately recognize and adapt to users' emotional states, enhancing the Metaverse experience across various applications. The proposed method is implemented using Python software. This adaptive approach significantly enhances users' immersion, emotional involvement, and overall satisfaction within the augmented reality environment by tailoring information to their responses. The findings show that the SVM-NLP emotion identification algorithm based on neuro-fuzzy, has a high degree of accuracy in recognizing emotional states, which holds promise for creating a Metaverse that is more emotionally compelling and immersive. Stronger humanâcomputer interactions and a wider range of applications, including virtual therapy, educational resources, entertainment, and social media networking, might be made possible by integrating SVM-NLP. These sophisticated systems are around 92% accurate in interpreting the emotions
Protective role of Withaferin-a on red blood cell integrity during 7,12-dimethylbenz[A]anthracene induced oral carcinogenesis
The aim of the present study was to investigate the protective effect of Withaferin-A on red blood cell integrity during 7,12-dimethylbenz[a]anthracene (DMBA) induced oral carcinogenesis. The protective effect of Withaferin-A was assessed by measuring the status of glycoconjugates, membrane bound enzyme activity and red blood cell osmotic fragility. Oral squamous cell carcinoma was induced in the buccal pouch of Syrian golden hamsters by painting with 0.5% DMBA in liquid paraffin thrice a week for 14 weeks. The levels of glycoconjugates, membrane bound enzyme activity, osmotic fragility and thiobarbituric acid reactive substances (TBARS) were analyzed by using specific colorimetric methods. We observed 100% tumor formation in DMBA painted hamsters. Increase in plasma glycoconjugates at the expense of red blood cell membrane glycoconjugates levels were observed in DMBA painted hamsters as compared to control hamsters. Erythrocytes from DMBA painted hamsters were more fragile than those from control hamsters. The activity of membrane bound enzyme (Na+ K+ ATPase) decreased whereas TBARS level was increased in DMBA painted hamsters as compared to control hamsters. Oral administration of Withaferin-A at a dose of 20mg kg-1 bw significantly prevented the tumor formation as well as normalized the biochemical variables in DMBA painted hamsters. Our results thus demonstrate the protective effect of Withaferin-A on red blood cell integrity during DMBA induced oral carcinogenesis.Key words: DMBA, Withaferin-A, Oral cancer, glycoconjugates, osmotic fragility
Role of dutasteride in preâclinical ETS fusionâpositive prostate cancer models
BACKGROUND Androgens play a crucial role in prostate cancer, hence the androgenic pathway has become an important target of therapeutic intervention. Previously we discovered that gene fusions between the 5âČâuntranslated region of androgen regulated gene TMPRSS2 and the ETS transcription factor family members were present in a majority of the prostate cancer cases. The resulting aberrant overexpression of ETS genes drives tumor progression. METHODS Here, we evaluated the expression levels of 5αâreductase isoenzymes in prostate cancer cell lines and tissues. We tested the effect of dutasteride, a 5αâreductase inhibitor, in TMPRSS2âERG fusionâpositive VCaP cell proliferation and cell invasion. We also evaluated the effect of dutasteride on the TMPRSS2âERG fusion gene expression. Finally, we tested dutasteride alone or in combination with an antiâandrogen in VCaP cell xenografts tumor model. RESULTS Our data showed that 5αâreductase SRD5A1 and SRD5A3 isoenzymes that are responsible for the conversion of testosterone to DHT, are highly expressed in metastatic prostate cancer compared to benign and localized prostate cancer. Dutasteride treatment attenuated VCaP cell proliferation and invasion. VCaP cells preâtreated with dutasteride showed a reduction in ERG and PSA expression. In vivo studies demonstrated that dutasteride in combination with the antiâandrogen bicalutamide significantly decreased tumor burden in VCaP cell xenograft model. CONCLUSIONS Our findings suggest that dutasteride can inhibit ERG fusionâpositive cell growth and in combination with antiâandrogen, significantly reduce the tumor burden. Our study suggests that antiâandrogens used in combination with dutasteride could synergistically augment the therapeutic efficacy in the treatment of ETSâpositive prostate cancer. Prostate 72:1542â1549, 2012. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93574/1/22509_ftp.pd
âTopological Significanceâ Analysis of Gene Expression and Proteomic Profiles from Prostate Cancer Cells Reveals Key Mechanisms of Androgen Response
The problem of prostate cancer progression to androgen independence has been extensively studied. Several studies systematically analyzed gene expression profiles in the context of biological networks and pathways, uncovering novel aspects of prostate cancer. Despite significant research efforts, the mechanisms underlying tumor progression are poorly understood. We applied a novel approach to reconstruct system-wide molecular events following stimulation of LNCaP prostate cancer cells with synthetic androgen and to identify potential mechanisms of androgen-independent progression of prostate cancer.We have performed concurrent measurements of gene expression and protein levels following the treatment using microarrays and iTRAQ proteomics. Sets of up-regulated genes and proteins were analyzed using our novel concept of "topological significance". This method combines high-throughput molecular data with the global network of protein interactions to identify nodes which occupy significant network positions with respect to differentially expressed genes or proteins. Our analysis identified the network of growth factor regulation of cell cycle as the main response module for androgen treatment in LNCap cells. We show that the majority of signaling nodes in this network occupy significant positions with respect to the observed gene expression and proteomic profiles elicited by androgen stimulus. Our results further indicate that growth factor signaling probably represents a "second phase" response, not directly dependent on the initial androgen stimulus.We conclude that in prostate cancer cells the proliferative signals are likely to be transmitted from multiple growth factor receptors by a multitude of signaling pathways converging on several key regulators of cell proliferation such as c-Myc, Cyclin D and CREB1. Moreover, these pathways are not isolated but constitute an interconnected network module containing many alternative routes from inputs to outputs. If the whole network is involved, a precisely formulated combination therapy may be required to fight the tumor growth effectively
Facile preparation of a cellulose microfibersâexfoliated graphite composite: a robust sensor for determining dopamine in biological samples
© 2017, Springer Science+Business Media B.V. A simple and robust dopamine (DA) sensor was developed using a cellulose microfibers (CMF)âexfoliated graphite composite-modified screen-printed carbon electrode (SPCE) for the first time. The graphite-CMF composite was prepared by sonication of pristine graphite in CMF solution and was characterized by high-resolution scanning electron microscopy, Fourier transform, infrared, and Raman spectroscopy. The cyclic voltammetry results reveal that the graphite-CMF composite modified SPCE has superior electrocatalytic activity against oxidation of dopamine than SPCE modified with pristine graphite and CMF. The presence of large edge plane defects on exfoliated graphite and abundant oxygen functional groups of CMF enhance electrocatalytic activity and decrease potential to oxidize DA. Differential pulse voltammetry was used to quantify DA using the graphite-CMF composite-modified SPCE and demonstrated a linear response for DA detection in the range of 0.06â134.5 ”M. The sensor shows a detection limit at 10 nM with an appropriate sensitivity and displays appropriate recovery of DA in human serum samples with good repeatability. Sensor selectivity is demonstrated in the presence of 50-fold concentrations of potentially active interfering compounds including ascorbic acid, uric acid, and dihydroxybenzene isomers
Metabolomic Profiling Reveals a Role for Androgen in Activating Amino Acid Metabolism and Methylation in Prostate Cancer Cells
Prostate cancer is the second leading cause of cancer related death in American men. Development and progression of clinically localized prostate cancer is highly dependent on androgen signaling. Metastatic tumors are initially responsive to anti-androgen therapy, however become resistant to this regimen upon progression. Genomic and proteomic studies have implicated a role for androgen in regulating metabolic processes in prostate cancer. However, there have been no metabolomic profiling studies conducted thus far that have examined androgen-regulated biochemical processes in prostate cancer. Here, we have used unbiased metabolomic profiling coupled with enrichment-based bioprocess mapping to obtain insights into the biochemical alterations mediated by androgen in prostate cancer cell lines. Our findings indicate that androgen exposure results in elevation of amino acid metabolism and alteration of methylation potential in prostate cancer cells. Further, metabolic phenotyping studies confirm higher flux through pathways associated with amino acid metabolism in prostate cancer cells treated with androgen. These findings provide insight into the potential biochemical processes regulated by androgen signaling in prostate cancer. Clinically, if validated, these pathways could be exploited to develop therapeutic strategies that supplement current androgen ablative treatments while the observed androgen-regulated metabolic signatures could be employed as biomarkers that presage the development of castrate-resistant prostate cancer
Proteomic Interrogation of Androgen Action in Prostate Cancer Cells Reveals Roles of Aminoacyl tRNA Synthetases
Prostate cancer remains the most common malignancy among men in United States, and there is no remedy currently available for the advanced stage hormone-refractory cancer. This is partly due to the incomplete understanding of androgen-regulated proteins and their encoded functions. Whole-cell proteomes of androgen-starved and androgen-treated LNCaP cells were analyzed by semi-quantitative MudPIT ESI- ion trap MS/MS and quantitative iTRAQ MALDI- TOF MS/MS platforms, with identification of more than 1300 high-confidence proteins. An enrichment-based pathway mapping of the androgen-regulated proteomic data sets revealed a significant dysregulation of aminoacyl tRNA synthetases, indicating an increase in protein biosynthesis- a hallmark during prostate cancer progression. This observation is supported by immunoblot and transcript data from LNCaP cells, and prostate cancer tissue. Thus, data derived from multiple proteomics platforms and transcript data coupled with informatics analysis provides a deeper insight into the functional consequences of androgen action in prostate cancer
Neighbours of cancer-related proteins have key influence on pathogenesis and could increase the drug target space for anticancer therapies
Even targeted chemotherapies against solid cancers show a moderate success increasing the need to novel targeting strategies. To address this problem, we designed a systems-level approach investigating the neighbourhood of mutated or differentially expressed cancer-related proteins in four major solid cancers (colon, breast, liver and lung). Using signalling and proteinâprotein interaction network resources integrated with mutational and expression datasets, we analysed the properties of the direct and indirect interactors (first and second neighbours) of cancer-related proteins, not found previously related to the given cancer type. We found that first neighbours have at least as high degree, betweenness centrality and clustering coefficient as cancer-related proteins themselves, indicating a previously unknown central network position. We identified a complementary strategy for mutated and differentially expressed proteins, where the affect of differentially expressed proteins having smaller network centrality is compensated with high centrality first neighbours. These first neighbours can be considered as key, so far hidden, components in cancer rewiring, with similar importance as mutated proteins. These observations strikingly suggest targeting first neighbours as a novel strategy for disrupting cancer-specific networks. Remarkably, our survey revealed 223 marketed drugs already targeting first neighbour proteins but applied mostly outside oncology, providing a potential list for drug repurposing against solid cancers. For the very central first neighbours, whose direct targeting would cause several side effects, we suggest a cancer-mimicking strategy by targeting their interactors (second neighbours of cancer-related proteins, having a central protein affecting position, similarly to the cancer-related proteins). Hence, we propose to include first neighbours to network medicine based approaches for (but not limited to) anticancer therapies
Propolis and swimming in the prevention of atherogenesis and left ventricular hypertrophy in hypercholesterolemic mice
Role of dutasteride in preâclinical ETS fusionâpositive prostate cancer models
BACKGROUND Androgens play a crucial role in prostate cancer, hence the androgenic pathway has become an important target of therapeutic intervention. Previously we discovered that gene fusions between the 5âČâuntranslated region of androgen regulated gene TMPRSS2 and the ETS transcription factor family members were present in a majority of the prostate cancer cases. The resulting aberrant overexpression of ETS genes drives tumor progression. METHODS Here, we evaluated the expression levels of 5αâreductase isoenzymes in prostate cancer cell lines and tissues. We tested the effect of dutasteride, a 5αâreductase inhibitor, in TMPRSS2âERG fusionâpositive VCaP cell proliferation and cell invasion. We also evaluated the effect of dutasteride on the TMPRSS2âERG fusion gene expression. Finally, we tested dutasteride alone or in combination with an antiâandrogen in VCaP cell xenografts tumor model. RESULTS Our data showed that 5αâreductase SRD5A1 and SRD5A3 isoenzymes that are responsible for the conversion of testosterone to DHT, are highly expressed in metastatic prostate cancer compared to benign and localized prostate cancer. Dutasteride treatment attenuated VCaP cell proliferation and invasion. VCaP cells preâtreated with dutasteride showed a reduction in ERG and PSA expression. In vivo studies demonstrated that dutasteride in combination with the antiâandrogen bicalutamide significantly decreased tumor burden in VCaP cell xenograft model. CONCLUSIONS Our findings suggest that dutasteride can inhibit ERG fusionâpositive cell growth and in combination with antiâandrogen, significantly reduce the tumor burden. Our study suggests that antiâandrogens used in combination with dutasteride could synergistically augment the therapeutic efficacy in the treatment of ETSâpositive prostate cancer. Prostate 72:1542â1549, 2012. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93574/1/22509_ftp.pd
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