Lithium is clinically used for the treatment of the bipolar manic disorder. In this study, we have evaluated its role in the wound healing process on the basis of our previous microarray studies where many genes relat...
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Lithium is clinically used for the treatment of the bipolar manic disorder. In this study, we have evaluated its role in the wound healing process on the basis of our previous microarray studies where many genes related to wound healing were upregulated. Formulations containing LiCl, poloxamer 407 (P407), alginate, and serum were prepared so as to make them "active" thermosensitive preparation, which may participate in different phases of wound healing. The formulations were analyzed for their physical properties, hemostasis, healing, hair regrowth, and expression of genes related to wound healing. The formulations showed a thermoreversible property, improved hemostasis in a liver laceration, and improved healing of full-thickness skin wound and hair regrowth in BALB/c mice and Sprague Dawley rat model. Further, we found genes which facilitate repair of the wound, e.g., TGF beta, COX2, and Col1a1, were also upregulated in RT-PCR assay. Particularly, we have detected the potential role of KRTAP10-2 gene in LiCl-induced hair regrowth. These formulations are likely to have application in the treatment of various injuries including accidents, trauma, diabetic wound, radiotherapy, war injuries, etc., where facilitated wound healing is essential. Lay Summary Our studies on microarray data analysis of LiCl-treated cells showed upregulation of wound healing genes. A formulation containing LiCl was evaluated in vitro and in vivo, which facilitated various stages of wound healing. The temperature-dependent phase changing property of this formulation makes it effective at places where the temperature remains subzero. The formulation may be prepared with other ingredients such as analgesics and antibiotics and could be packed as per the requirement such as spray, cream, gel, etc. Future Studies The formulation may further be evaluated in the GLP (Good Laboratory Practice) setting;this may help in the repurposing of LiCl and other constituents for wound healing purpose.
Background: Neuropathic pain is a common chronic pain, characterized by spontaneous pain and mechanical allodynia. The incidence of neuropathic pain is on the rise due to infections, higher rates of diabetes and strok...
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Background: Neuropathic pain is a common chronic pain, characterized by spontaneous pain and mechanical allodynia. The incidence of neuropathic pain is on the rise due to infections, higher rates of diabetes and stroke, and increased use of chemotherapy drugs in cancer patients. At present, due to its pathophysiological process and molecular mechanism remaining unclear, there is a lack of effective treatment and prevention methods in clinical practice. Now, we use bioinformatics technology to integrate and filter hub genes that may be related to the pathogenesis of neuropathic pain, and explore their possible molecular mechanism by functional annotation and pathway enrichment analysis. Methods: The expression profiles of GSE24982, GSE2884, GSE2636 and GSE30691 were downloaded from the Gene Expression Omnibus(GEO)database, and these datasets include 93 neuropathic pain Rattus norvegicus and 59 shame controls. After the four datasets were all standardized by quantiles, the differentially expressed genes (DEGs) between NPP Rattus norvegicus and the shame controls were finally identified by the robust rank aggregation (RRA) analysis method. In order to reveal the possible underlying biological function of DEGs, the Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway enrichment analysis of DEGs were performed. In addition, a Protein-protein Interaction (PPI) network was also established. At the end of our study, a high throughput sequencing dataset GSE117526 was used to corroborate our calculation ***: Through RRA analysis of the above four datasets GSE24982, GSE2884, GSE2636, and GSE30691, we finally obtained 231 DEGs, including 183 up-regulated genes and 47 down-regulated genes. Arranging 231 DEGs in descending order according to |log2 fold change (FC)|, we found that the top 20 key genes include 14 up -regulated genes and 6 down-regulated genes. The most down-regulated hub gene abnormal expressed in NPP was E
Traditional computational techniques are recently being improved with the use of prior biological knowledge from open-access repositories in the area of gene expression dataanalysis. In this work, we propose the use ...
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Traditional computational techniques are recently being improved with the use of prior biological knowledge from open-access repositories in the area of gene expression dataanalysis. In this work, we propose the use of prior knowledge as heuristic in an inference method of gene-gene associations from gene expression profiles. In this paper, we use Gene Ontology, which is an open-access ontology where genes are annotated using their biological functionality, as a source of prior knowledge together with a gene pairwise Gene-Ontology-based measure. The performance of our proposal has been compared to other benchmark methods for the inference of gene networks, outperforming in some cases and obtaining similar and competitive results in others, but with the advantage of providing simple and interpretable models, which is a desired feature for the Artificial Intelligence Health related models as stated by the European Union.
Purpose: Lithium chloride (LiCl) is clinically used for manic disorders. Its role has been shown in improving cell survival by decreasing Bax and p53 expression and increasing Bcl-2 concentration in the cell. This pot...
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Purpose: Lithium chloride (LiCl) is clinically used for manic disorders. Its role has been shown in improving cell survival by decreasing Bax and p53 expression and increasing Bcl-2 concentration in the cell. This potential of LiCl is responsible for reducing irradiated cell death. In this study, we have explored the role of LiCl as a radioprotectant affecting survival genes. Materials and methods: To find out the cellular response upon LiCl pretreatment to radiation-exposed KG1a cells;viability, clonogenic assay and microarray studies were performed. This was followed by the detection of transcription factor binding motif in coregulated genes. These results were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and chromatin immunoprecipitation (CHIP). Results: LiCl improved irradiated KG1a cell survival and its clonogenicity at 2 mM concentration (clinically used). microarray data analysis showed differential expression of cell-protecting genes playing an important role in apoptosis, cell cycle, adhesion and inflammation, etc. The coregulation analysis revealed genes involved in bile acid biosynthesis were also affected by LiCl treatment, these genes are likely to be responsible for radiation-induced gastrointestinal (GI) syndrome through bile production. Conclusions: This is the first study with respect to global genetic expression upon LiCl treatment to radiation-exposed cells. Our results suggest considering repurposing of LiCl as a protective agent for radiation injury.
Cancer has been identified as the leading cause of death. It is predicted that around 20-26 million people will be diagnosed with cancer by 2020. With this alarming rate, there is an urgent need for a more effective m...
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Cancer has been identified as the leading cause of death. It is predicted that around 20-26 million people will be diagnosed with cancer by 2020. With this alarming rate, there is an urgent need for a more effective methodology to understand, prevent and cure cancer. microarray technology provides a useful basis of achieving this goal, with cluster analysis of gene expression data leading to the discrimination of patients, identification of possible tumor subtypes and individualized treatment. Amongst clustering techniques, k-means is normally chosen for its simplicity and efficiency. However, it does not account for the different importance of data attributes. This paper presents a new locally weighted extension of k-means, which has proven more accurate across many published datasets than the original and other extensions found in the literature.
Several research areas are being faced with data matrices that are not suitable to be managed with traditional clustering, regression, or classification strategies. For example, biological so-called omic problems pres...
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ISBN:
(纸本)9783030617059;9783030617042
Several research areas are being faced with data matrices that are not suitable to be managed with traditional clustering, regression, or classification strategies. For example, biological so-called omic problems present models with thousands or millions of rows and less than a hundred columns. This matrix structure hinders the successful progress of traditional dataanalysis methods and thus needs some means for reducing the number of rows. This article presents an unsupervised approach called PreCLAS for preprocessing matrices with dimension problems to obtain data that are apt for clustering and classification strategies. The PreCLAS was implemented as an unsupervised strategy that aims at finding a submatrix with a drastically reduced number of rows, preferring those rows that together present some group structure. Experimentation was carried out in two stages. First, to assess its functionality, a benchmark dataset was studied in a clustering context. Then, a microarraydataset with genomic information was analyzed, and the PreCLAS was used to select informative genes in the context of classification strategies. Experimentation showed that the new method performs successfully at drastically reducing the number of rows of a matrix, smartly performing unsupervised feature selection for both classification and clustering problems.
Background: microarray data analysis presents a significant challenge to researchers who are unable to use the powerful Bioconductor and its numerous tools due to their lack of knowledge of R language. Among the few e...
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Glycan and lectin microarrays are two arising technologies, very important to the glycomics field. Glycomics is the science that focuses on defining the structures and functions of carbohydrates in nature. These micro...
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ISBN:
(纸本)9789897583988
Glycan and lectin microarrays are two arising technologies, very important to the glycomics field. Glycomics is the science that focuses on defining the structures and functions of carbohydrates in nature. These microarrays provide information regarding the interactions between specific carbohydrates and proteins, and it has many applications in clinical and research settings. Nevertheless, the availability of analytical software for these types of arrays is very limited, so researchers usually perform data processing and analytical pipelines manually, which is very time consuming and prone to error. SugarArray was born as a user-friendly and intuitive stand-alone solution that process the intensity data generated from glycan or lectin array studies, and displays the results to the user in an understandable manner The solution also allows the users to manage the data as needed, create data plots and automatically generate reports. This tool was intended to simplify the processing steps of the analytical pipeline, so the users can focus on what really matters: understanding the results.
Feature selection is a common solution to microarrayanalysis. Previous approaches either select features based on classical statistical tests that can be tuned up with a classifier, or using regularization penalties ...
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Feature selection is a common solution to microarrayanalysis. Previous approaches either select features based on classical statistical tests that can be tuned up with a classifier, or using regularization penalties incorporated in the cost function. Here we propose to use a feature ranking and weighting scheme instead, which combines statistical techniques with a weighted k-NN classifier using a modified forward selection procedure. We demonstrate that classification accuracy of our proposal outperforms existing methods on a range of public microarray gene expression datasets. The proposed method is also compared to state-of-the-art feature selection algorithms by means of the Friedman test. Although a bunch of feature selection techniques has been used for genomic data, the experimental results show the classification superiority of our method on most of the present gene expression datasets.
Background and objective: Finding combinations (i.e., pairs, or more generally, q-tuples with q >= 2) of genes whose behavior as a group differs significantly between two classes has received a lot of attention in ...
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Background and objective: Finding combinations (i.e., pairs, or more generally, q-tuples with q >= 2) of genes whose behavior as a group differs significantly between two classes has received a lot of attention in the quest for the discovery of simple, accurate, and easily interpretable decision rules for disease classification and prediction. For example, the Top Scoring Pair (TSP) method seeks to find pairs of genes so that the probability of the reversal of the relative ranking of the expression levels of the genes in the two classes is maximized. The computational cost of finding a q-tuple of genes that scores highest under a given metric is O(G(q)), where G is the total number of genes. This cost is often problematic or prohibitive in practice (even for q = 2), as the number of genes G is often in the order of tens of thousands. Methods: In this paper, we show that this computational cost can be significantly reduced by excluding from consideration genes whose behavior is almost identical in the two classes and therefore their inclusion in any q-tuple is rather non-informative. Our criterion for the exclusion of genes is supported by a statistically robust metric, the Area Under the Curve (AUC) of the corresponding Receiver Operating Characteristic (ROC) curve. By filtering out genes whose AUC value is below a user-chosen threshold, as determined by a procedure that we describe in the paper, dramatic reductions in the run times are obtained while maintaining the same classification accuracy. Results: We have experimentally verified the gains of this approach on several case studies involving ovarian, colon, leukemia, breast and prostate cancers, and diffuse large b-cell lymphoma. Conclusions: The proposed method is not only faster (for example, we observed an average 78.65% reduction over the run time of TSP) while maintaining the same classification accuracy, but it can even result in better classification accuracy due to its inherent ability to avoid the so-c
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