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Smart cities have emerged as a specialized domain encompassing various technologies, transitioning from civil engineering to technology-driven solutions. The accelerated development of technologies, such as the Internet of Things (IoT), software-defined networks (SDN), 5G, artificial intelligence, cognitive science, and analytics, has played a crucial role in providing solutions for smart cities. Smart cities heavily rely on devices, ad hoc networks, and cloud computing to integrate and streamline various activities towards common goals. However, the complexity arising from multiple cloud service providers offering myriad services necessitates a stable and coherent platform for sustainable operations. The Smart City Operational Platform Ecology (SCOPE) model has been developed to address the growing demands, and incorporates machine learning, cognitive correlates, ecosystem management, and security. SCOPE provides an ecosystem that establishes a balance for achieving sustainability and progress. In the context of smart cities, Internet of Things (IoT) devices play a significant role in enabling automation and data capture. This research paper focuses on a specific module of SCOPE, which deals with data processing and learning mechanisms for object identification in smart cities. Specifically, it presents a car parking system that utilizes smart identification techniques to identify vacant slots. The learning controller in SCOPE employs a two-tier approach, and utilizes two different models, namely Alex Net and YOLO, to ensure procedural stability and improvement.
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Mutations of the tyrosine kinase-directed ubiquitin ligase CBL cause myeloid leukemias, but the molecular determinants of the dominant leukemogenic activity of mutant CBL oncogenes are unclear. Here, we first define a gain-of-function attribute of the most common leukemia-associated CBL mutant, Y371H, by demonstrating its ability to increase proliferation of hematopoietic stem/progenitor cells (HSPCs) derived from CBL-null and CBL/CBL-B-null mice. Next, we express second-site point/deletion mutants of CBL-Y371H in CBL/CBL-B-null HSPCs or the cytokine-dependent human leukemic cell line TF-1 to show that individual or combined Tyr â Phe mutations of established phosphotyrosine residues (Tyr-700, Tyr-731, and Tyr-774) had little impact on the activity of the CBL-Y371H mutant in HSPCs, and the triple Tyr â Phe mutant was only modestly impaired in TF-1 cells. In contrast, intact tyrosine kinase-binding (TKB) domain and proline-rich region (PRR) were critical in both cell models. PRR deletion reduced the stem cell factor (SCF)-induced hyper-phosphorylation of the CBL-Y371H mutant and the c-KIT receptor and eliminated the sustained p-ERK1/2 and p-AKT induction by SCF. GST fusion protein pulldowns followed by phospho-specific antibody array analysis identified distinct CBL TKB domains or PRR-binding proteins that are phosphorylated in CBL-Y371H-expressing TF-1 cells. Our results support a model of mutant CBL gain-of-function in which mutant CBL proteins effectively compete with the remaining wild type CBL-B and juxtapose TKB domain-associated PTKs with PRR-associated signaling proteins to hyper-activate signaling downstream of hematopoietic growth factor receptors. Elucidation of mutant CBL domains required for leukemogenesis should facilitate targeted therapy approaches for patients with mutant CBL-driven leukemias.
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Proteínas Mutantes/química , Mutação , Oncogenes , Proteínas Proto-Oncogênicas c-cbl/química , Animais , Sítios de Ligação , Linhagem Celular Tumoral , Separação Celular , Citocinas/metabolismo , Citometria de Fluxo , Regulação Leucêmica da Expressão Gênica , Glutationa Transferase/metabolismo , Células-Tronco Hematopoéticas/citologia , Humanos , Camundongos , Camundongos Knockout , Mutagênese , Proteínas Mutantes/genética , Fenótipo , Fenilalanina/química , Fosforilação , Prolina/química , Domínios Proteicos , Proteínas Proto-Oncogênicas c-cbl/genética , Proteínas Recombinantes de Fusão/química , Transdução de Sinais , Tirosina/químicaRESUMO
PURPOSE: The main purpose of this study was to formulate an oil-in-water nanoemulsion of a next generation taxoid DHA-SBT-1214 and evaluate its biodistribution and pharmacokinetics. METHODS: DHA-SBT-1214 was encapsulated in a fish oil containing nanoemulsion using a high pressure homogenization method. Following morphological characterization of the nanoemulsions, qualitative and quantitative biodistribution was evaluated in naïve and cancer stem cell-enriched PPT-2 human prostate tumor bearing mice. RESULTS: DHA-SBT-1214 was successfully encapsulated up to 20 mg/ml in the nanoemulsion formulation and had an average oil droplet size of 200 nm. Using a DiR near infra-red dye encapsulated nanoemulsion, we have shown the delivery of nanoemulsion to mouse tumor region. By quantitative analysis, DHA-SBT-1214 encapsulated nanoemulsion demonstrated improved pharmacokinetic properties in plasma and different tissues as compared to its solution form. Furthermore, the nanoemulsions were stable and had slower in vitro drug release compared to its solution form. CONCLUSIONS: The results from this study demonstrated effective encapsulation of the drug in a nanoemulsion and this nanoemulsion showed sustained plasma levels and enhanced tumor delivery relative to the solution form.
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Antineoplásicos/farmacocinética , Ácidos Docosa-Hexaenoicos/farmacocinética , Composição de Medicamentos/métodos , Neoplasias/tratamento farmacológico , Taxoides/farmacocinética , Administração Intravenosa , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Linhagem Celular Tumoral , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/química , Liberação Controlada de Fármacos , Emulsões , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Nanopartículas/química , Taxoides/administração & dosagem , Taxoides/química , Distribuição Tecidual , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: Cisplatin, is recognized as a first line therapeutic for the treatment of non-small cell lung cancer (NSCLC). Cisplatin resistance is identified as the most detrimental complication during treatment and has been associated with upregulation of several genes, such as the anti-apoptotic gene survivin. In this study, we have evaluated the cytotoxic activity of lipid (C6 and C8)-modified platinum compounds in combination with a survivin-silencing siRNA against cisplatin resistant tumors. METHODS: We synthesized and characterized several lipid-modified platinum compounds and evaluated their cytotoxic activity alone or in combination with survivin-silencing siRNA in vitro and in vivo against A549DDP cells and in vivo in tumor xenograft model. RESULTS: The lipid-modified compounds exhibited significantly stronger cytotoxic activity in vitro compared to cisplatin, with CDDP-C6 and CDDP-C8 producing the most pronounced effect, in both A549 and A549DDP cells. Pre-treatment of the A549DDP cells with survivin-silencing siRNA enhanced the cytotoxic activity of these compounds. In vivo, the co-treatment of the survivin-silencing siRNA and CDDP-C8 produced the strongest tumor growth inhibition effect (64.5%, p < 0.05) on a cancer mouse model of chemoresistant lung cancer. In contrast, cisplatin treatment exhibited no significant tumor growth inhibition (4.5%, no p). CONCLUSIONS: Co-treatment of lipid-modified compounds and survivin-silencing siRNA can constitute a reliable alternative to cisplatin treatment for cisplatin-resistant lung tumors that merit further evaluation.
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Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/análogos & derivados , Cisplatino/uso terapêutico , Proteínas Inibidoras de Apoptose/genética , Lipídeos/química , Neoplasias Pulmonares/tratamento farmacológico , RNA Interferente Pequeno/genética , Células A549 , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Apoptose , Carcinoma Pulmonar de Células não Pequenas/genética , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Feminino , Inativação Gênica , Humanos , Ácido Hialurônico/química , Neoplasias Pulmonares/genética , Camundongos Nus , Nanopartículas/química , Polietilenoglicóis/química , Polietilenoimina/química , SurvivinaRESUMO
ErbB2 overexpression drives oncogenesis in 20-30% cases of breast cancer. Oncogenic potential of ErbB2 is linked to inefficient endocytic traffic into lysosomes and preferential recycling. However, regulation of ErbB2 recycling is incompletely understood. We used a high-content immunofluorescence imaging-based kinase inhibitor screen on SKBR-3 breast cancer cells to identify kinases whose inhibition alters the clearance of cell surface ErbB2 induced by Hsp90 inhibitor 17-AAG. Less ErbB2 clearance was observed with broad-spectrum PKC inhibitor Ro 31-8220. A similar effect was observed with Go 6976, a selective inhibitor of classical Ca(2+)-dependent PKCs (α, ß1, ßII, and γ). PKC activation by PMA promoted surface ErbB2 clearance but without degradation, and ErbB2 was observed to move into a juxtanuclear compartment where it colocalized with PKC-α and PKC-δ together with the endocytic recycling regulator Arf6. PKC-α knockdown impaired the juxtanuclear localization of ErbB2. ErbB2 transit to the recycling compartment was also impaired upon PKC-δ knockdown. PMA-induced Erk phosphorylation was reduced by ErbB2 inhibitor lapatinib, as well as by knockdown of PKC-δ but not that of PKC-α. Our results suggest that activation of PKC-α and -δ mediates a novel positive feedback loop by promoting ErbB2 entry into the endocytic recycling compartment, consistent with reported positive roles for these PKCs in ErbB2-mediated tumorigenesis. As the endocytic recycling compartment/pericentrion has emerged as a PKC-dependent signaling hub for G-protein-coupled receptors, our findings raise the possibility that oncogenesis by ErbB2 involves previously unexplored PKC-dependent endosomal signaling.
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Antineoplásicos/farmacologia , Proteína Quinase C-alfa/metabolismo , Proteína Quinase C-delta/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Receptor ErbB-2/metabolismo , Benzoquinonas/farmacologia , Neoplasias da Mama , Carbazóis/farmacologia , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Endocitose/efeitos dos fármacos , Endossomos/metabolismo , Ativação Enzimática , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Retroalimentação Fisiológica , Feminino , Humanos , Indóis/farmacologia , Lactamas Macrocíclicas/farmacologia , Sistema de Sinalização das MAP Quinases , Fosforilação , Proteína Quinase C-alfa/antagonistas & inibidores , Proteína Quinase C-delta/antagonistas & inibidores , Processamento de Proteína Pós-Traducional , Transporte ProteicoRESUMO
Protein tyrosine kinases (PTKs) coordinate a broad spectrum of cellular responses to extracellular stimuli and cell-cell interactions during development, tissue homeostasis, and responses to environmental challenges. Thus, an understanding of the regulatory mechanisms that ensure physiological PTK function and potential aberrations of these regulatory processes during diseases such as cancer are of broad interest in biology and medicine. Aside from the expected role of phospho-tyrosine phosphatases, recent studies have revealed a critical role of covalent modification of activated PTKs with ubiquitin as a critical mechanism of their negative regulation. Members of the Cbl protein family (Cbl, Cbl-b and Cbl-c in mammals) have emerged as dominant "activated PTK-selective" ubiquitin ligases. Structural, biochemical and cell biological studies have established that Cbl protein-dependent ubiquitination targets activated PTKs for degradation either by facilitating their endocytic sorting into lysosomes or by promoting their proteasomal degradation. This mechanism also targets PTK signaling intermediates that become associated with Cbl proteins in a PTK activation-dependent manner. Cellular and animal studies have established that the relatively broadly expressed mammalian Cbl family members Cbl and Cbl-b play key physiological roles, including their critical functions to prevent the transition of normal immune responses into autoimmune disease and as tumor suppressors; the latter function has received validation from human studies linking mutations in Cbl to human leukemia. These newer insights together with embryonic lethality seen in mice with a combined deletion of Cbl and Cbl-b genes suggest an unappreciated role of the Cbl family proteins, and by implication the ubiquitin-dependent control of activated PTKs, in stem/progenitor cell maintenance. Future studies of existing and emerging animal models and their various cell lineages should help test the broader implications of the evolutionarily-conserved Cbl family protein-mediated, ubiquitin-dependent, negative regulation of activated PTKs in physiology and disease.
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Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-cbl/fisiologia , Ubiquitinação/fisiologia , Sequência de Aminoácidos , Animais , Humanos , Camundongos , Modelos Biológicos , Proteínas Tirosina Quinases/fisiologia , Proteínas Proto-Oncogênicas c-cbl/genética , Proteínas Proto-Oncogênicas c-cbl/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Ubiquitina/metabolismoRESUMO
The emergence of computer technologies and computing power has led to the development of several database systems that provide standardized access to vast quantities of data, making it possible to collect, search, index, evaluate, and extract useful knowledge across various fields. The Home of All Biological Databases (HABD) has been established as a continually expanding platform that aims to store, organize, and distribute biological data in a searchable manner, removing all dead and non-accessible data. The platform meticulously categorizes data into various categories, such as COVID-19 Pandemic Database (CO-19PDB), Database relevant to Human Research (DBHR), Cancer Research Database (CRDB), Latest Database of Protein Research (LDBPR), Fungi Databases Collection (FDBC), and many other databases that are categorized based on biological phenomena. It currently provides a total of 22 databases, including 6 published, 5 submitted, and the remaining in various stages of development. These databases encompass a range of areas, including phytochemical-specific and plastic biodegradation databases. HABD is equipped with search engine optimization (SEO) analyzer and Neil Patel tools, which ensure excellent SEO and high-speed value. With timely updates, HABD aims to facilitate the processing and visualization of data for scientists, providing a one-stop-shop for all biological databases. Computer platforms, such as PhP, html, CSS, Java script and Biopython, are used to build all the databases. © 2024 Wiley Periodicals LLC.
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COVID-19 , Bases de Dados Factuais , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Ferramenta de Busca , Pesquisa BiomédicaRESUMO
The ubiquitination of transmembrane receptors regulates endocytosis, intracellular traffic, and signal transduction. Bone marrow-derived macrophages from myeloid Cbl-/- and Cbl-b-/- double knockout (DKO) mice display sustained proliferation mirroring the myeloproliferative disease that these mice succumb to. Here, we found that the ubiquitin ligases Cbl and Cbl-b have overlapping functions for controlling the endocytosis and intracellular traffic of the CSF-1R. DKO macrophages displayed complete loss of ubiquitination of the CSF-1R whereas partial ubiquitination was observed for either single Cbl-/- or Cbl-b-/- macrophages. Unlike wild type, DKO macrophages were immortal and displayed slower CSF-1R internalization, elevated AKT signaling, and a failure to transport the CSF-1R into the lumen of nascent macropinosomes, leaving its cytoplasmic region available for signaling. CSF-1R degradation depended upon lysosomal vATPase activity in both WT and DKO macrophages, with this degradation confined to macropinosomes in WT but occurring in distributed/tubular lysosomes in DKO cells. RNA-sequencing comparison of Cbl-/-, Cbl-b-/- and DKO macrophages indicated that while the overall macrophage transcriptional program remained intact, DKO macrophages had alterations in gene expression associated with growth factor signaling, cell cycle, inflammation and senescence. Cbl-b-/- had minimal effect on the transcriptional program whereas Cbl-/- led to more alternations but only DKO macrophages demonstrated substantial changes in the transcriptome, suggesting overlapping but unique functions for the two Cbl-family members. Thus, Cbl/Cbl-b-mediated ubiquitination of CSF-1R regulates its endocytic fate, constrains inflammatory gene expression, and regulates signaling for macrophage proliferation.
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Receptor de Fator Estimulador de Colônias de Macrófagos , Ubiquitina , Camundongos , Animais , Ubiquitina/metabolismo , Receptor de Fator Estimulador de Colônias de Macrófagos/metabolismo , Fator Estimulador de Colônias de Macrófagos/genética , Fator Estimulador de Colônias de Macrófagos/metabolismo , Fator Estimulador de Colônias de Macrófagos/farmacologia , Proteínas Proto-Oncogênicas c-cbl/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Macrófagos/metabolismoRESUMO
Aim: Head and Neck squamous cell carcinoma (HNSCC) is the second most prevalent cancer in Pakistan. Methods: Gene expression data from TCGA and GETx for normal genes to analyze Differentially Expressed Genes (DEGs). Data was further investigated using the Enrichr tool to perform Gene Ontology (GO). Results: Our analysis identified most significantly differentially expressed genes and explored their established cellular functions as well as their potential involvement in tumor development. We found that the highly expressed Keratin family and S100A9 genes. The under-expressed genes KRT4 and KRT13 provide instructions for the production of keratin proteins. Conclusion: Our study suggests that factors such as poor oral hygiene and smokeless tobacco can result in oral stress and cellular damage and cause cancer.
The Cancer Genome Atlas (TCGA) holds vast cancer data processed with powerful computers and cloud tech. This sparks new bioinformatics for better cancer diagnosis, treatment, and prevention. In Southeast Asia, Head and Neck Squamous Cell Carcinoma (HNSCC) is prevalent. We used TCGA and GETx data to study gene expression. High-expression Keratin and S100A9 genes fight cellular damage under stress, while under-expressed KRT4 and KRT13 genes shape cell structure. Poor oral care and smokeless tobacco could induce cell damage, sparking cancer mutations. Unveiling HNSCC mechanisms may guide targeted treatments and preventive strategies.
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Biological databases serve as critical basics for modern research, and amid the dynamic landscape of biology, the COVID-19 database has emerged as an indispensable resource. The global outbreak of Covid-19, commencing in December 2019, necessitates comprehensive databases to unravel the intricate connections between this novel virus and cancer. Despite existing databases, a crucial need persists for a centralized and accessible method to acquire precise information within the research community. The main aim of the work is to develop a database which has all the COVID-19-related data available in just one click with auto global notifications. This gap is addressed by the meticulously designed COVID-19 Pandemic Database (CO-19 PDB 2.0), positioned as a comprehensive resource for researchers navigating the complexities of COVID-19 and cancer. Between December 2019 and June 2024, the CO-19 PDB 2.0 systematically collected and organized 120 datasets into six distinct categories, each catering to specific functionalities. These categories encompass a chemical structure database, a digital image database, a visualization tool database, a genomic database, a social science database, and a literature database. Functionalities range from image analysis and gene sequence information to data visualization and updates on environmental events. CO-19 PDB 2.0 has the option to choose either the search page for the database or the autonotification page, providing a seamless retrieval of information. The dedicated page introduces six predefined charts, providing insights into crucial criteria such as the number of cases and deaths', country-wise distribution, 'new cases and recovery', and rates of death and recovery. The global impact of COVID-19 on cancer patients has led to extensive collaboration among research institutions, producing numerous articles and computational studies published in international journals. A key feature of this initiative is auto daily notifications for standardized information updates. Users can easily navigate based on different categories or use a direct search option. The study offers up-to-date COVID-19 datasets and global statistics on COVID-19 and cancer, highlighting the top 10 cancers diagnosed in the USA in 2022. Breast and prostate cancers are the most common, representing 30% and 26% of new cases, respectively. The initiative also ensures the removal or replacement of dead links, providing a valuable resource for researchers, healthcare professionals, and individuals. The database has been implemented in PHP, HTML, CSS and MySQL and is available freely at https://www.co-19pdb.habdsk.org/. Database URL: https://www.co-19pdb.habdsk.org/.
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COVID-19 , Neoplasias , Pandemias , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/virologia , Humanos , Neoplasias/epidemiologia , Bases de Dados Factuais , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Betacoronavirus , Bases de Dados de ProteínasRESUMO
Objective: Urinary bladder cancer (UBC) is the fourth most common cancer among men and tenth most common cancer in women. This study investigated an association of interleukins -17A promoter region single nucleotide polymorphism (SNP)-rs2275913 with UBC in Pakistani population. Methods: Population-based study was designed with 127 UBC patients and 100 healthy individuals. Only UBC Patients were included and other diseases hepatitis or any other malignancy/cancer were excluded from the study. Polymerase chain reaction Restriction fragment length polymorphism technique was used to genotype the rs2275913 SNP in patients and control. Linear regression analysis was performed on the genotype data and allelic frequency data. Online statistical tool was used to calculate ratio of odds. Results: Linear regression analysis showed that there was no association between rs2275913 SNP and UBC patients in the dominant model (OR = 0.815, CI = 0.415-1.6), recessive model (OR = 0.389, CI = 0.014-5.565), codominant model (OR = 0.376, CI=0.013-5.420) and (OR = 0.855, CI = 0.427-1.713). Moreover, among the UBC samples, low-grade non-muscle invasive UBC samples dominant model (OR = 0.722, CI = 0.316-1.637), recessive model (OR = 0.000, CI = 0.000-5.864), codominant model (OR = 0.864, CI = 0.030-12.668), and (OR = 0.788, CI = 0.341-1.806) did also not show any association. When same analysis was performed for high-grade muscle invasive UBC, dominant (OR = 0.936, CI = 0.403-2.155), recessive model (OR = 0.875, CI = 0.031-12.696), and codominant model (OR = 0.864, CI = 0.030-12.668,), and (OR = 0.942, CI = 0.394-2.232) did not show any association. Conclusion: Results revealed that rs2275913 did not show any associated with the high risk of UBC in Pakistani population. Some limitations of the studies are firstly, the samples size and other are detailed information on UBC and role of inflammation.
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Serious illnesses caused by viruses are becoming the world's most critical public health issues and lead millions of deaths each year in the world. Thousands of studies confirmed that the plant-derived medicines could play positive therapeutic effects on the patients with viral diseases. Since thousands of antiviral phytochemicals have been identified as lifesaving drugs in medical research, a comprehensive database is highly desirable to integrate the medicinal plants with their different medicinal properties. Therefore, we provided a friendly antiviral phytochemical database AVPCD covering 2537 antiviral phytochemicals from 383 medicinal compounds and 319 different families with annotation of their scientific, family and common names, along with the parts used, disease information, active compounds, links of relevant articles for COVID-19, cancer, HIV and malaria. Furthermore, each compound in AVPCD was annotated with its 2D and 3D structure, molecular formula, molecular weight, isomeric SMILES, InChI, InChI Key and IUPAC name and 21 other properties. Each compound was annotated with more than 20 properties. Specifically, a scoring method was designed to measure the confidence of each phytochemical for the viral diseases. In addition, we constructed a user-friendly platform with several powerful modules for searching and browsing the details of all phytochemicals. We believe this database will facilitate global researchers, drug developers and health practitioners in obtaining useful information against viral diseases.
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COVID-19 , Infecções por HIV , Malária , Neoplasias , Humanos , Antivirais , Neoplasias/tratamento farmacológico , Malária/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Infecções por HIV/tratamento farmacológicoRESUMO
Objective: The green synthesis method for nanoparticles is getting more attention globally, due to its lesser cost, non-hazardous, and eco-friendly nature. The novelty of the present work is to investigate the anti-bacterial and degradation activity of the green synthesized Iron Oxide NPs. Methods: In this study, the Iron Oxide NPs were synthesized through a green synthesis route from leaves of Ficus Palmata. UV-Vis confirmed Iron Oxide NP's peaks between (230-290 nm), while Fourier transforms infrared spectroscopy analysis showed that several groups were involved in reduction and stabilization. Results: Results indicated that the highest photo thermal activity was shown in light and it was almost 4 folds greater than the control. Similarly, Iron Oxide NPs showed excellent antimicrobial potential against bacterial species "Salmonella typhi" "Xanthomonas Oryzae" and "Lactobacillus" at low concentrations (150 µg/mL). Hemolytic assay results showed that the toxicity was lesser than 5% at both dark and light conditions. Moreover, we also evaluated the photo-catalytic potential of Iron Oxide NPs against methylene orange. Results indicated that almost complete degradation was noted after 90 min in the presence of continuous light. All tests were performed in triplicates. All the data was subjected to P-test (P < 0.5) using Excel and graph pad (V.5.0). Conclusion: Iron Oxide NPs holds a promising future and could be used in treating diseases, and microbial pathogenesis and also could be used as a vector in drug delivery. Moreover, they can also eradicate persistent dyes and could be used as an alternative to remediate pollutants from the environment.
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BACKGROUND: The achievement of the human genome project provides a basis for the systematic study of the human genome from evolutionary history to disease-specific medicine. With the explosive growth of biological data, a growing number of biological databases are being established to support human-related research. OBJECTIVE: The main objective of our study is to store, organize and share data in a structured and searchable manner. In short, we have planned the future development of new features in the database research area. MATERIALS & METHODS: In total, we collected and integrated 680 human databases from scientific published work. Multiple options are presented for accessing the data, while original links and short descriptions are also presented for each database. RESULTS & DISCUSSION: We have provided the latest collection of human research databases on a single platform with six categories: DNA database, RNA database, protein database, expression database, pathway database and disease database. CONCLUSION: Taken together, our database will be useful for further human research study and will be modified over time. The database has been implemented in PHP, HTML, CSS and MySQL and is available freely at https://habdsk.org/database.php.
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BACKGROUND: The advancement of cancer research has been facilitated through freely available cancer literature, databases, and tools. The age of genomics and big data has given rise to the need for cooperation and data sharing in order to make efficient use of this new information in the COVID-19 pandemic. Although there are many databases for cancer research, their access is not easy owing to different ways of processing and managing the data. There is an absence of a unified platform to manage all of them in a transparent and more comprehensible way. OBJECTIVE: In this study, an improved integrated cancer research database and platform is provided to facilitate a deeper statistical insight into the correlation between cancer and the COVID-19 pandemic, unifying the collection of almost all previous published cancer databases and defining a model web database for cancer research, and scoring databases on the basis of the variety types of cancer, sample size, completeness of omics results, and user interface. METHODS: Databases examined and integrated include the Data Portal database, Genomic database, Proteomic database, Expression database, Gene database, and Mutation database; and it is expected that this launch will sort, save, advance the understanding and encourage the use of these resources in the cancer research environment. RESULTS: To make it easy to search valuable information, 85 cancer databases are provided in the form of a table, and a database of databases named the Cancer Research Database (CRDB) has been built and presented herein. Furthermore, the CRDB has been herein equipped with unique navigation tools in order to be explored by three methods; that is, any single database can be browsed by typing the name in the given search bar, while all categories can be browsed by clicking on the name of the category or image expression icon, thus serving as a facility that could provide all the category databases on a single click. CONCLUSIONS: The computational platform (PHP, HTML, CSS, and MySQL) used to build CRDB for the cancer scientific community can be freely investigated and browsed on the internet and is planned to be updated in a timely manner. In addition, based on the proposed platform, the status and diagnoses statistics of cancer during the COVID-19 pandemic have been thoroughly investigated herein using CRDB, thus providing an easy-to-manage, understandable framework that mines knowledge for future researchers.
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Immune-activating cytokines such as interleukin-12 (IL-12) hold strong potential for cancer immunotherapy but have been limited by high systemic toxicities. We describe here an approach to safely harness cytokine biology for adoptive cell therapy through uniform and dose-controlled tethering onto the surface of the adoptively transferred cells. Tumor-specific T cells tethered with IL-12 showed superior antitumor efficacy across multiple cell therapy models compared to conventional systemic IL-12 coadministration. Mechanistically, the IL-12-tethered T cells supported a strong safety profile by driving interferon-γ production and adoptively transferred T cell activity preferentially in the tumor. Immune profiling revealed that the tethered IL-12 reshaped the suppressive tumor immune microenvironment, including triggering a pronounced repolarization of monocytic myeloid-derived suppressor cells into activated, inflammatory effector cells that further supported antitumor activity. This tethering approach thus holds strong promise for harnessing and directing potent immunomodulatory cytokines for cell therapies while limiting systemic toxicities.
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Interleucina-12 , Neoplasias , Terapia Baseada em Transplante de Células e Tecidos , Citocinas , Humanos , Imunoterapia Adotiva , Neoplasias/terapia , Microambiente TumoralRESUMO
In this article, a new method is developed to design a three-band miniaturized bandpass filter (BPF) that uses two asymmetrically coupled resonators with one step discontinuity and open-circuited uniform impedance resonator (UIR) to achieve Global Interoperability with Microwave Access (WiMAX) and Radio Frequency Identification (RFID) applications. First, a pair of asymmetrical step impedance resonators (ASIR) is used to implement a dual band filter, then a half wavelength uniform impedance resonator is added below to the transmission line to achieve a triple band response. The proposed filter resonates at frequencies of 3.7 GHz, 6.6 GHz, and 9 GHz with the fractional bandwidth of 7.52%, 5.1%, and 4.44%, respectively. By adjusting the physical length ratio (α) and the impedance ratio (R) of the asymmetric SIR, the proposed fundamental frequencies of the triple BPF are obtained. Moreover, the coupling coefficient (Ke) and external quality factor (Qe) are investigated between the resonators and the input/output ports of the transmission line and are calculated using full-wave EM simulator HFSS. In addition, five transmission zeros are introduced near the passbands to increase the filter selectivity. Finally, the proposed filter is designed and fabricated with a size of 13.69 × 25 mm (0.02 λg × 0.03 λg), where λg represents the guiding wavelength in the first passband. The simulated and measured results have a good correspondence, thus confirming the design concept.
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Eletrônica , Impedância ElétricaRESUMO
BACKGROUND: The current coronavirus disease-19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global outbreak of a disease from a new coronavirus. Several databases have been published on this pandemic, but the research community still needs an easy way to get comprehensive information on COVID-19. OBJECTIVES: COVID-19 pandemic database (CO-19 PDB) aims to provide wonderful insights for COVID-19 researchers with the well-gathered of all the COVID-19 data to one platform, which is a global challenge for the research community these days. METHODS: We gathered 59 updated databases since December-2019 until May 2021 and divided them into six categories: digital image database, genomic database, literature database, visualization tools database, chemical structure database, and social science database. These categories focus on taking number of functions from the images, information from gene sequences, updates from relevant papers, essays, reports, articles, and books, the data or information in the form of maps, graphs, and charts, information of bonds between atoms, and updates about events of the physical and social environment, respectively. RESULTS: Users can search the information of interest in two ways including typing the name of the database in the search bar or by clicking the right category directly. Computer languages such as CSS, PHP, HTML, Java, etc. are utilized to construct CO-19 PDB. CONCLUSION: This article attempts to compile up-to-date appropriate COVID-19 datasets and resources that have not been compiled and given in such an accessible and user-friendly manner. As a result, the CO-19 PDB offers extensive open data sharing for both worldwide research communities and local people. Further, we have planned future development of new features, that will be awesome for future study.
RESUMO
The goal of this study was to evaluate combination of a novel taxoid, DHA-SBT-1214 chemotherapy, in modulating immune checkpoint marker expression and ultimately in improving antibody-based checkpoint blockade therapy in pancreatic adenocarcinoma (PDAC). DHA-SBT-1214 was encapsulated in an oil-in-water nanoemulsion and administered systemically in Panc02 syngeneic PDAC-bearing C57BL/6 mice. Following treatment with DHA-SBT-1214, expression levels of PD-L1 were measured and anti-PD-L1 antibody was administered in combination. The effects of combination therapy on efficacy and the molecular basis of synergistic effects were evaluated. PD-L1 expression was lower on Panc02 pancreatic tumor cells in vitro, which significantly increased after exposure to different chemotherapy drugs. Administration of DHA-SBT-1214, gemcitabine, and PD-L1 antibody alone failed to increase CD8+ T-cell infiltration inside tumors. However, combination of anti-PD-L1 therapy with a novel chemotherapy drug DHA-SBT-1214 in nanoemulsion (NE-DHA-SBT-1214) significantly enhanced CD8+ T-cell infiltration and the therapeutic effects of the anti-PD-L1 antibody. Furthermore, in the Panc02 syngeneic model, the NE-DHA-SBT-1214 combination therapy group reduced tumor growth to a higher extend than paclitaxel, nab-paclitaxel (Abraxane), gemcitabine, or single anti-PD-L1 antibody therapy groups. Our results indicate that NE-DHA-SBT-1214 stimulated immunogenic potential of PDAC and provided an enhanced therapeutic effect with immune checkpoint blockade therapy, which warrants further evaluation.
Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Antígeno B7-H1/metabolismo , Carcinoma Ductal Pancreático/tratamento farmacológico , Ácidos Docosa-Hexaenoicos/química , Neoplasias Pancreáticas/tratamento farmacológico , Taxoides/administração & dosagem , Animais , Antineoplásicos Imunológicos/farmacologia , Antígeno B7-H1/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Composição de Medicamentos , Sinergismo Farmacológico , Emulsões , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Taxoides/química , Taxoides/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
In this research, a new multilayered mamdani fuzzy inference system (Ml-MFIS) is proposed to diagnose hepatitis B. The proposed automated diagnosis of hepatitis B using multilayer mamdani fuzzy inference system (ADHB-ML-MFIS) expert system can classify the different stages of hepatitis B such as no hepatitis, acute HBV, or chronic HBV. The expert system has two input variables at layer I and seven input variables at layer II. At layer I, input variables are ALT and AST that detect the output condition of the liver to be normal or to have hepatitis or infection and/or other problems. The further input variables at layer II are HBsAg, anti-HBsAg, anti-HBcAg, anti-HBcAg-IgM, HBeAg, anti-HBeAg, and HBV-DNA that determine the output condition of hepatitis such as no hepatitis, acute hepatitis, or chronic hepatitis and other reasons that arise due to enzyme vaccination or due to previous hepatitis infection. This paper presents an analysis of the results accurately using the proposed ADHB-ML-MFIS expert system to model the complex hepatitis B processes with the medical expert opinion that is collected from the Pathology Department of Shalamar Hospital, Lahore, Pakistan. The overall accuracy of the proposed ADHB-ML-MFIS expert system is 92.2%.