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  1. Article ; Online: Mebendazole targets essential proteins in glucose metabolism leading gastric cancer cells to death.

    da Silva, Emerson Lucena / Mesquita, Felipe Pantoja / Aragão, Dyane Rocha / de Sousa Portilho, Adrhyann Jullyanne / Marinho, Aline Diogo / de Oliveira, Lais Lacerda Brasil / Lima, Luina Benevides / de Moraes, Maria Elisabete Amaral / Souza, Pedro Filho Noronha / Montenegro, Raquel Carvalho

    Toxicology and applied pharmacology

    2023  Volume 475, Page(s) 116630

    Abstract: Gastric cancer (GC) is among the most-diagnosed and deadly malignancies worldwide. Deregulation in cellular bioenergetics is a hallmark of cancer. Based on the importance of metabolic reprogramming for the development and cancer progression, inhibitors ... ...

    Abstract Gastric cancer (GC) is among the most-diagnosed and deadly malignancies worldwide. Deregulation in cellular bioenergetics is a hallmark of cancer. Based on the importance of metabolic reprogramming for the development and cancer progression, inhibitors of cell metabolism have been studied as potential candidates for chemotherapy in oncology. Mebendazole (MBZ), an antihelminthic approved by FDA, has shown antitumoral activity against cancer cell lines. However, its potential in the modulation of tumoral metabolism remains unclear. Results evidenced that the antitumoral and cytotoxic mechanism of MBZ in GC cells is related to the modulation of the mRNA expression of glycolic targets SLC2A1, HK1, GAPDH, and LDHA. Moreover, in silico analysis has shown that these genes are overexpressed in GC samples, and this increase in expression is related to decreased overall survival rates. Molecular docking revealed that MBZ modifies the protein structure of these targets, which may lead to changes in their protein function. In vitro studies also showed that MBZ induces alterations in glucose uptake, LDH's enzymatic activity, and ATP production. Furthermore, MBZ induced morphologic and intracellular alterations typical of the apoptotic cell death pathway. Thus, this data indicated that the cytotoxic mechanism of MBZ is related to an initial modulation of the tumoral metabolism in the GC cell line. Altogether, our results provide more evidence about the antitumoral mechanism of action of MBZ towards GC cells and reveal metabolic reprogramming as a potential area in the discovery of new pharmacological targets for GC chemotherapy.
    MeSH term(s) Humans ; Mebendazole/pharmacology ; Mebendazole/therapeutic use ; Stomach Neoplasms/drug therapy ; Cell Line, Tumor ; Molecular Docking Simulation ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Glucose
    Chemical Substances Mebendazole (81G6I5V05I) ; Antineoplastic Agents ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2023-07-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 204477-8
    ISSN 1096-0333 ; 0041-008X
    ISSN (online) 1096-0333
    ISSN 0041-008X
    DOI 10.1016/j.taap.2023.116630
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.B 14: Show issues Location:
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  2. Article: Kinase Inhibitor Screening Displayed

    Mesquita, Felipe Pantoja / Souza, Pedro Filho Noronha / da Silva, Emerson Lucena / Lima, Luina Benevides / de Oliveira, Lais Lacerda Brasil / Moreira-Nunes, Caroline Aquino / Zuercher, William J / Burbano, Rommel Mario Rodríguez / de Moraes, Maria Elisabete Amaral / Montenegro, Raquel Carvalho

    Pharmaceutics

    2022  Volume 14, Issue 9

    Abstract: Despite advances in cancer chemotherapy, gastric cancer (GC) continues to have high recurrence rates and poor prognosis with limited treatment options. Understanding the etiology of GC and developing more effective, less harmful therapeutic approaches ... ...

    Abstract Despite advances in cancer chemotherapy, gastric cancer (GC) continues to have high recurrence rates and poor prognosis with limited treatment options. Understanding the etiology of GC and developing more effective, less harmful therapeutic approaches are vital and urgent. Therefore, this work describes a novel kinase target in malignant gastric cells as a potential therapeutic strategy. Our results demonstrate that among 147 kinase inhibitors (KI), only three molecules were significantly cytotoxic for the AGP-01 cell line. Hence, these three molecules were further characterized in their cellular mode of action. There was significant cell cycle impairment due to the expression modulation of genes such as
    Language English
    Publishing date 2022-09-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics14091841
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  3. Article ; Online: Mebendazole targets essential proteins in glucose metabolism leading gastric cancer cells to death

    da Silva, Emerson Lucena / Mesquita, Felipe Pantoja / Aragão, Dyane Rocha / de Sousa Portilho, Adrhyann Jullyanne / Marinho, Aline Diogo / de Oliveira, Lais Lacerda Brasil / Lima, Luina Benevides / de Moraes, Maria Elisabete Amaral / Souza, Pedro Filho Noronha / Montenegro, Raquel Carvalho

    Toxicology and Applied Pharmacology. 2023 Sept., v. 475 p.116630-

    2023  

    Abstract: Gastric cancer (GC) is among the most-diagnosed and deadly malignancies worldwide. Deregulation in cellular bioenergetics is a hallmark of cancer. Based on the importance of metabolic reprogramming for the development and cancer progression, inhibitors ... ...

    Abstract Gastric cancer (GC) is among the most-diagnosed and deadly malignancies worldwide. Deregulation in cellular bioenergetics is a hallmark of cancer. Based on the importance of metabolic reprogramming for the development and cancer progression, inhibitors of cell metabolism have been studied as potential candidates for chemotherapy in oncology. Mebendazole (MBZ), an antihelminthic approved by FDA, has shown antitumoral activity against cancer cell lines. However, its potential in the modulation of tumoral metabolism remains unclear. Results evidenced that the antitumoral and cytotoxic mechanism of MBZ in GC cells is related to the modulation of the mRNA expression of glycolic targets SLC2A1, HK1, GAPDH, and LDHA. Moreover, in silico analysis has shown that these genes are overexpressed in GC samples, and this increase in expression is related to decreased overall survival rates. Molecular docking revealed that MBZ modifies the protein structure of these targets, which may lead to changes in their protein function. In vitro studies also showed that MBZ induces alterations in glucose uptake, LDH's enzymatic activity, and ATP production. Furthermore, MBZ induced morphologic and intracellular alterations typical of the apoptotic cell death pathway. Thus, this data indicated that the cytotoxic mechanism of MBZ is related to an initial modulation of the tumoral metabolism in the GC cell line. Altogether, our results provide more evidence about the antitumoral mechanism of action of MBZ towards GC cells and reveal metabolic reprogramming as a potential area in the discovery of new pharmacological targets for GC chemotherapy.
    Keywords apoptosis ; cell lines ; computer simulation ; cytotoxicity ; death ; drug therapy ; energy metabolism ; enzyme activity ; gene expression ; glucose ; mebendazole ; mechanism of action ; neoplasm cells ; neoplasm progression ; pharmacology ; protein structure ; stomach neoplasms ; toxicology ; Antitumoral ; Drug repurposing ; Glycolytic pathway ; Metabolic reprogramming ; Molecular docking ; Pharmacologic targets
    Language English
    Dates of publication 2023-09
    Publishing place Elsevier Inc.
    Document type Article ; Online
    Note Pre-press version
    ZDB-ID 204477-8
    ISSN 1096-0333 ; 0041-008X
    ISSN (online) 1096-0333
    ISSN 0041-008X
    DOI 10.1016/j.taap.2023.116630
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 76/516: Show issues

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  4. Article: Anticancer potential of mebendazole against chronic myeloid leukemia:

    Daniel, Julio Paulino / Mesquita, Felipe Pantoja / Da Silva, Emerson Lucena / de Souza, Pedro Filho Noronha / Lima, Luina Benevides / de Oliveira, Lais Lacerda Brasil / de Moraes, Maria Elisabete Amaral / Moreira-Nunes, Caroline de Fátima Aquino / Burbano, Rommel Mario Rodríguez / Zanatta, Geancarlo / Montenegro, Raquel Carvalho

    Frontiers in pharmacology

    2022  Volume 13, Page(s) 952250

    Abstract: Chronic myeloid leukemia (CML) is caused by constitutively active fusion protein BCR-ABL1, and targeting ABL1 is a promising therapy option. Imatinib, dasatinib, and nilotinib have all been shown to work effectively in clinical trials. ABL1 mutations, ... ...

    Abstract Chronic myeloid leukemia (CML) is caused by constitutively active fusion protein BCR-ABL1, and targeting ABL1 is a promising therapy option. Imatinib, dasatinib, and nilotinib have all been shown to work effectively in clinical trials. ABL1 mutations, particularly the T315I gate-keeper mutation, cause resistance in patients. As a result, broad-spectrum ABL1 medicines are desperately needed. In order to screen potential drugs targeting CML, mebendazole (MBZ) was subjected to the
    Language English
    Publishing date 2022-08-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2022.952250
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Post-COVID-19 Cognitive Decline and Apoe Polymorphism: Towards a Possible Link?

    Tavares-Júnior, José Wagner Leonel / Oliveira, Danilo Nunes / da Silva, Jean Breno Silveira / Queiroz Feitosa, Werbety Lucas / Sousa, Artur Victor Menezes / Marinho, Samuel Cavalcante / Cunha, Letícia Chaves Vieira / Gaspar, Safira de Brito / Gomes, Carmem Meyve Pereira / de Oliveira, Laís Lacerda Brasil / Moreira-Nunes, Caroline Aquino / Sobreira, Emmanuelle Silva Tavares / Moraes, Maria Elisabete Amaral de / Sobreira-Neto, Manoel Alves / Montenegro, Raquel Carvalho / Braga-Neto, Pedro

    Brain sciences

    2023  Volume 13, Issue 12

    Abstract: ... ...

    Abstract APOE
    Language English
    Publishing date 2023-11-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2651993-8
    ISSN 2076-3425
    ISSN 2076-3425
    DOI 10.3390/brainsci13121611
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Genomic surveillance: Circulating lineages and genomic variation of SARS-CoV-2 in early pandemic in Ceará state, Northeast Brazil

    Oliveira, Francisca Andréa da Silva / de Holanda, Maísa Viana / Lima, Luína Benevides / Dantas, Mariana Brito / Duarte, Igor Oliveira / de Castro, Luzia Gabrielle Zeferino / de Oliveira, Laís Lacerda Brasil / Paier, Carlos Roberto Koscky / Moreira-Nunes, Caroline de Fátima Aquino / Lima, Nicholas Costa Barroso / de Moraes, Maria Elisabete Amaral / de Moraes Filho, Manoel Odorico / Melo, Vânia Maria Maciel / Montenegro, Raquel Carvalho

    Virus research. 2022 Nov., v. 321

    2022  

    Abstract: In the Northeast of Brazil, Ceará was the second state most impacted by COVID-19 in number of cases and death rate. Despite that, the early dynamics of the pandemic in Ceará was not yet well understood due the low genomic surveillance of SARS-CoV-2 in ... ...

    Abstract In the Northeast of Brazil, Ceará was the second state most impacted by COVID-19 in number of cases and death rate. Despite that, the early dynamics of the pandemic in Ceará was not yet well understood due the low genomic surveillance of SARS-CoV-2 in 2020. In this study, we analyze the circulating lineages and the genomic variation of the virus in Ceará state. Thirty-four genomes were sequenced and combined with sequences available in GISAID database from March 2020 to June 2021 to compose the study dataset. The most prevalent lineages detected were B.1.1.33, in 2020, and P.1, in 2021. Other lineages were found, such as P.2, sublineages of P.1, B.1, B.1.1, B.1.1.28 and B.1.212. Analyzing the mutations, a total of 202 single-nucleotide polymorphisms (SNPs) were identified among the 34 genomes sequenced, of which 127 were missense, 74 synonymous, and one was a nonsense mutation. Among the missense mutations, C14408T, A23403G, T27299C, G28881A G28883C, and T29148C were the most prevalent within the dataset. Although SARS-CoV-2 sequencing data was limited in 2020, our results could provide insights to better understand the genetic diversity of the circulating lineages in Ceará.
    Keywords COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; data collection ; databases ; genetic variation ; genome ; genomics ; monitoring ; mortality ; nonsense mutation ; pandemic ; research ; viruses ; Brazil
    Language English
    Dates of publication 2022-11
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 605780-9
    ISSN 1872-7492 ; 0168-1702
    ISSN (online) 1872-7492
    ISSN 0168-1702
    DOI 10.1016/j.virusres.2022.198908
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1965: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  7. Article: Long-covid cognitive impairment: Cognitive assessment and apolipoprotein E (APOE) genotyping correlation in a Brazilian cohort.

    Tavares-Júnior, José Wagner Leonel / Oliveira, Danilo Nunes / da Silva, Jean Breno Silveira / Feitosa, Werbety Lucas Queiroz / Sousa, Artur Victor Menezes / Cunha, Letícia Chaves Vieira / Gaspar, Safira de Brito / Gomes, Carmem Meyve Pereira / de Oliveira, Laís Lacerda Brasil / Moreira-Nunes, Caroline Aquino / Montenegro, Raquel Carvalho / Sobreira-Neto, Manoel Alves / Braga-Neto, Pedro

    Frontiers in psychiatry

    2022  Volume 13, Page(s) 947583

    Abstract: Introduction: Few studies have objectively evaluated cognitive deficits after the acute phase of COVID-19 disease. Moreover, the role of apolipoprotein E (APOE) genotypes in cognitive decline in patients with COVID-19 has not been evaluated yet.: ... ...

    Abstract Introduction: Few studies have objectively evaluated cognitive deficits after the acute phase of COVID-19 disease. Moreover, the role of apolipoprotein E (APOE) genotypes in cognitive decline in patients with COVID-19 has not been evaluated yet.
    Methods: This cross-sectional study was conducted in confirmed cases of COVID-19 patients with neurological symptoms that persisted for more than 3 months from the onset. We determined APOE genotypes.
    Results: The final sample consisted of 141 patients. The most frequent APOE genotype was E3/E3 (
    Discussion: Hospitalized patients had more severe infection with a greater possibility of systemic complications, greater inflammatory response, and prolonged hospitalization, which could impact cognitive performance. Cognitive impairment in patients with COVID-19 does not necessarily involve specific APOE polymorphisms. However, psychiatric disorders may also be responsible for cognitive complaints. Cognitive complaints are frequent in patients with COVID-19, even after the acute phase of the disease and in mild cases. Hospitalized participants and depressed patients may have a higher risk of cognitive impairment. APOE genotypes or haplotypes may not significantly play a role in COVID-19 cognitive impairment.
    Language English
    Publishing date 2022-08-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564218-2
    ISSN 1664-0640
    ISSN 1664-0640
    DOI 10.3389/fpsyt.2022.947583
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Genomic surveillance: Circulating lineages and genomic variation of SARS-CoV-2 in early pandemic in Ceará state, Northeast Brazil.

    Oliveira, Francisca Andréa da Silva / de Holanda, Maísa Viana / Lima, Luína Benevides / Dantas, Mariana Brito / Duarte, Igor Oliveira / de Castro, Luzia Gabrielle Zeferino / de Oliveira, Laís Lacerda Brasil / Paier, Carlos Roberto Koscky / Moreira-Nunes, Caroline de Fátima Aquino / Lima, Nicholas Costa Barroso / de Moraes, Maria Elisabete Amaral / de Moraes Filho, Manoel Odorico / Melo, Vânia Maria Maciel / Montenegro, Raquel Carvalho

    Virus research

    2022  Volume 321, Page(s) 198908

    Abstract: In the Northeast of Brazil, Ceará was the second state most impacted by COVID-19 in number of cases and death rate. Despite that, the early dynamics of the pandemic in Ceará was not yet well understood due the low genomic surveillance of SARS-CoV-2 in ... ...

    Abstract In the Northeast of Brazil, Ceará was the second state most impacted by COVID-19 in number of cases and death rate. Despite that, the early dynamics of the pandemic in Ceará was not yet well understood due the low genomic surveillance of SARS-CoV-2 in 2020. In this study, we analyze the circulating lineages and the genomic variation of the virus in Ceará state. Thirty-four genomes were sequenced and combined with sequences available in GISAID database from March 2020 to June 2021 to compose the study dataset. The most prevalent lineages detected were B.1.1.33, in 2020, and P.1, in 2021. Other lineages were found, such as P.2, sublineages of P.1, B.1, B.1.1, B.1.1.28 and B.1.212. Analyzing the mutations, a total of 202 single-nucleotide polymorphisms (SNPs) were identified among the 34 genomes sequenced, of which 127 were missense, 74 synonymous, and one was a nonsense mutation. Among the missense mutations, C14408T, A23403G, T27299C, G28881A G28883C, and T29148C were the most prevalent within the dataset. Although SARS-CoV-2 sequencing data was limited in 2020, our results could provide insights to better understand the genetic diversity of the circulating lineages in Ceará.
    MeSH term(s) Humans ; Brazil/epidemiology ; Codon, Nonsense ; COVID-19/epidemiology ; Genome, Viral ; Genomics ; Mutation ; Pandemics ; Phylogeny ; SARS-CoV-2/genetics
    Chemical Substances Codon, Nonsense
    Language English
    Publishing date 2022-08-31
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 605780-9
    ISSN 1872-7492 ; 0168-1702
    ISSN (online) 1872-7492
    ISSN 0168-1702
    DOI 10.1016/j.virusres.2022.198908
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1965: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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