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  • 1
    Online Resource
    Online Resource
    High-Throughput Drug Screening Revealed That Ciclopirox Olamine Can Engender Gastric Cancer Stem-like Cells
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 17 ( 2023-09-03), p. 4406-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 17 ( 2023-09-03), p. 4406-
    Abstract: Cancer stem cells (CSCs) are relevant therapeutic targets for cancer treatment. Still, the molecular circuits behind CSC characteristics are not fully understood. The low number of CSCs can sometimes be an obstacle to carrying out assays that explore their properties. Thus, increasing CSC numbers via small molecule-mediated cellular reprogramming appears to be a valid alternative tool. Using the SORE6-GFP reporter system embedded in gastric non-CSCs (SORE6−), we performed a high-throughput image-based drug screen with 1200 small molecules to identify compounds capable of converting SORE6− to SORE6+ (CSCs). Here, we report that the antifungal agent ciclopirox olamine (CPX), a potential candidate for drug repurposing in cancer treatment, is able to reprogram gastric non-CSCs into cancer stem-like cells via activation of SOX2 expression and increased expression of C-MYC, HIF-1α, KLF4, and HMGA1. This reprogramming depends on the CPX concentration and treatment duration. CPX can also induce cellular senescence and the metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis. We also disclose that the mechanism underlying the cellular reprogramming is similar to that of cobalt chloride (CoCl2), a hypoxia-mimetic agent.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15174406
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 2
    Online Resource
    Online Resource
    Genetic Diversity and Population Genetic Structure of a Guzerá (Bos indicus) Meta-Population
    MDPI AG ; 2021
    In:  Animals Vol. 11, No. 4 ( 2021-04-14), p. 1125-
    Details
    In: Animals, MDPI AG, Vol. 11, No. 4 ( 2021-04-14), p. 1125-
    Abstract: The Brazilian Guzerá population originated from a few founders introduced from India. These animals adapted well to the harsh environments in Brazil, were selected for beef, milk, or dual-purpose (beef and milk), and were extensively used to produce crossbred animals. Here, the impact of these historical events with regard to the population structure and genetic diversity in a Guzerá meta-population was evaluated. DNA samples of 744 animals (one dairy, nine dual-purpose, and five beef herds) were genotyped for 21 microsatellite loci. Ho, He, PIC, Fis, Fit, and Fst estimates were obtained considering either farms or lineages as subpopulations. Mean Ho (0.73) and PIC (0.75) suggest that genetic diversity was efficiently conserved. Fit, Fis and Fst values (95% CI) pointed to a low fixation index, and large genetic diversity: Fit (Farms = 0.021–0.100; lineages = 0.021–0.100), Fis (Farms = –0.007–0.076; lineages = −0.014–0.070), and Fst (Farms = 0.0237–0.032; lineages = 0.029–0.038). The dual-purpose herds/selection lines are the most uniform subpopulation, while the beef one preserved larger amounts of genetic diversity among herds. In addition, the dairy herd showed to be genetically distant from other herds. Taken together, these results suggest that this Guzerá meta-population has high genetic diversity, a low degree of population subdivision, and a low inbreeding level.
    Type of Medium: Online Resource
    ISSN: 2076-2615
    URL: Article
    DOI: 10.3390/ani11041125
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2606558-7
    SSG: 23
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  • 3
    Online Resource
    Online Resource
    High VEGFA Expression Is Associated with Improved Progression-Free Survival after Bevacizumab Treatment in Recurrent Glioblastoma
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 8 ( 2023-04-07), p. 2196-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 8 ( 2023-04-07), p. 2196-
    Abstract: Glioblastoma (GB) is one of the deadliest human cancers. Many GB patients do not respond to treatment, and inevitably die within a median of 15–18 months post-diagnosis, highlighting the need for reliable biomarkers to aid clinical management and treatment evaluation. The GB microenvironment holds tremendous potential as a source of biomarkers; several proteins such as MMP-2, MMP-9, YKL40, and VEGFA have been identified as being differentially expressed in GB patient samples. Still to date, none of these proteins have been translated into relevant clinical biomarkers. This study evaluated the expression of MMP-2, MMP-9, YKL40, and VEGFA in a series of GBs and their impact on patient outcome. High levels of VEGFA expression were significantly associated with improved progression-free survival after bevacizumab treatment, thus having potential as a tissue biomarker for predicting patients’ response to bevacizumab. Noteworthily, VEGFA expression was not associated with patient outcome after temozolomide treatment. To a lesser extent, YKL40 also provided significant information regarding the extent of bevacizumab treatment. This study highlights the importance of studying secretome-associated proteins as GB biomarkers and identifies VEGFA as a promising marker for predicting response to bevacizumab.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15082196
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 4
    Online Resource
    Online Resource
    Exploring the Diversity and Biotechnological Potential of Cultured and Uncultured Coral-Associated Bacteria
    MDPI AG ; 2021
    In:  Microorganisms Vol. 9, No. 11 ( 2021-10-27), p. 2235-
    Details
    In: Microorganisms, MDPI AG, Vol. 9, No. 11 ( 2021-10-27), p. 2235-
    Abstract: Coral-associated microbes are crucial for the biology of their hosts, contributing to nutrient cycling, adaptation, mitigation of toxic compounds, and biological control of pathogens. Natural products from coral-associated micro-organisms (CAM) may possess unique traits. Despite this, the use of CAM for biotechnological purposes has not yet been adequately explored. Here, we investigated the production of commercially important enzymes by 37 strains of bacteria isolated from the coral species Mussismilia braziliensis, Millepora alcicornis, and Porites astreoides. In-vitro enzymatic assays showed that up to 56% of the isolates produced at least one of the seven enzymes screened (lipase, caseinase, keratinase, cellulase, chitinase, amylase, and gelatinase); one strain, identified as Bacillus amyloliquefaciens produced all these enzymes. Additionally, coral species-specific cultured and uncultured microbial communities were identified. The phylum Firmicutes predominated among the isolates, including the genera Exiguobacterium, Bacillus, and Halomonas, among others. Next-generation sequencing and bacteria culturing produced similar but also complementary data, with certain genera detected only by one or the other method. Our results demonstrate the importance of exploring different coral species as sources of specific micro-organisms of biotechnological and industrial interest, at the same time reinforcing the economic and ecological importance of coral reefs as reservoirs of such diversity.
    Type of Medium: Online Resource
    ISSN: 2076-2607
    URL: Article
    DOI: 10.3390/microorganisms9112235
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2720891-6
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  • 5
    Online Resource
    Online Resource
    Red Sea Atlas of Coral-Associated Bacteria Highlights Common Microbiome Members and Their Distribution across Environmental Gradients—A Systematic Review
    MDPI AG ; 2022
    In:  Microorganisms Vol. 10, No. 12 ( 2022-11-26), p. 2340-
    Details
    In: Microorganisms, MDPI AG, Vol. 10, No. 12 ( 2022-11-26), p. 2340-
    Abstract: The Red Sea is a suitable model for studying coral reefs under climate change due to its strong environmental gradient that provides a window into future global warming scenarios. For instance, corals in the southern Red Sea thrive at temperatures predicted to occur at the end of the century in other biogeographic regions. Corals in the Red Sea thrive under contrasting thermal and environmental regimes along their latitudinal gradient. Because microbial communities associated with corals contribute to host physiology, we conducted a systematic review of the known diversity of Red Sea coral-associated bacteria, considering geographic location and host species. Our assessment comprises 54 studies of 67 coral host species employing cultivation-dependent and cultivation-independent techniques. Most studies have been conducted in the central and northern Red Sea, while the southern and western regions remain largely unexplored. Our data also show that, despite the high diversity of corals in the Red Sea, the most studied corals were Pocillopora verrucosa, Dipsastraea spp., Pleuractis granulosa, and Stylophora pistillata. Microbial diversity was dominated by bacteria from the class Gammaproteobacteria, while the most frequently occurring bacterial families included Rhodobacteraceae and Vibrionaceae. We also identified bacterial families exclusively associated with each of the studied coral orders: Scleractinia (n = 125), Alcyonacea (n = 7), and Capitata (n = 2). This review encompasses 20 years of research in the Red Sea, providing a baseline compendium for coral-associated bacterial diversity.
    Type of Medium: Online Resource
    ISSN: 2076-2607
    URL: Article
    DOI: 10.3390/microorganisms10122340
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720891-6
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  • 6
    Online Resource
    Online Resource
    Chrysin Modulates Genes Related to Inflammation, Tissue Remodeling, and Cell Proliferation in the Gastric Ulcer Healing
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 3 ( 2020-01-23), p. 760-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 3 ( 2020-01-23), p. 760-
    Abstract: Chrysin exhibits anti-inflammatory and antioxidant activities. Here, the gastroprotective effect of chrysin was investigated in mouse models of gastric ulcer induced by absolute ethanol, acetic acid, and ischemia-reperfusion injury. The gastric-healing effect was evaluated at 7 and 14 days after treatment; the mechanism of action was verified using the expression of metalloproteinase 2 (MMP-2) and 9 (MMP-9), caspase-3, cyclooxygenase 1 (COX-1) and 2 (COX-2), epidermal growth factor (EGF), and interleukin-10. Chrysin (10 mg/kg) inhibited macroscopic lesions and increased catalase activity in the mouse model established using absolute ethanol. It ameliorated the gastric ulcer caused by acetic acid by improving the expression of inflammatory genes such as COX-2, inhibiting negative remodeling promoted by MMP-9, increasing cell proliferation effect via EGF, and reducing cellular apoptosis by modulating caspase-3. A faster healing effect was evident in the first 7 days of treatment compared to 14 days of treatment, indicating the pharmacological potential of chrysin. Overall, these results demonstrate the potent effect of chrysin in the gastrointestinal tract and elucidate the genes involved in the healing of gastric ulcers. Moreover, an increase in the levels of gastric mucosa defensive factors is involved in the activity of chrysin in the gastric mucosa.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21030760
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Multiple Micronutrient Powder Reduces Vitamin E Deficiency in Brazilian Children: A Pragmatic, Controlled Clinical Trial
    MDPI AG ; 2019
    In:  Nutrients Vol. 11, No. 11 ( 2019-11-11), p. 2730-
    Details
    In: Nutrients, MDPI AG, Vol. 11, No. 11 ( 2019-11-11), p. 2730-
    Abstract: Multiple micronutrient powder supplementation is a health promotion strategy, but data on its effectiveness regarding vitamin E are rare. The objective was to evaluate the impact of home fortification with powdered micronutrients on α-tocopherol concentrations, growth, and inflammation in Brazilian children aged 6–15 months. This is a pragmatic, controlled clinical trial, in which the intervention group received micronutrient powder sachets for up to 3 months. Vitamin E deficiency was considered when α-tocopherol was less than 11.6 µmol/L. The Poisson regression model was used to estimate adjusted values for prevalence ratios (PR) for the outcome variable. A total of 224 children participated in the study. The intervention group had a higher median α-tocopherol level (17.2 versus 3.6 µmol/L; p 〈 0.001) and an 82.0% reduction in the prevalence of vitamin deficiency (PR = 0.18; 95% CI 0.11–0.30) when compared with the control group. Consumption of multiple micronutrients in powder increases serum α-tocopherol concentrations, promotes better linear growth, and reduces morbidity in children.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu11112730
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2518386-2
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  • 8
    Online Resource
    Online Resource
    Frequency of CDH1, CTNNA1 and CTNND1 Germline Variants in Families with Diffuse and Mixed Gastric Cancer
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 17 ( 2023-08-29), p. 4313-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 17 ( 2023-08-29), p. 4313-
    Abstract: The most well-characterized hereditary form of gastric cancer is hereditary diffuse gastric cancer (HDGC), an autosomal dominant syndrome characterized by an increased risk of diffuse gastric and lobular breast cancer. HDGC is predominantly caused by germline pathogenic variants in the CDH1 gene, and more rarely in the CTNNA1 gene. Furthermore, the International Gastric Cancer Linkage Consortium (IGCLC) guidelines do not clarify whether or not mixed gastric cancer (with a diffuse component) should be considered in the HDGC genetic testing criteria. We aimed to evaluate the contribution of CTNNA1 and CTNND1 germline variants to HDGC. Additionally, we also intended to compare the frequencies of CDH1 and CTNNA1 (and eventually CTNND1) germline variants between patients with diffuse and mixed gastric carcinomas to evaluate if genetic testing for these genes should or should not be considered in patients with the latter. We analyzed the CDH1 gene in 67 cases affected with early-onset/familial mixed gastric carcinomas and the CTNNA1 and CTNND1 genes in 208 cases with diffuse or mixed gastric cancer who had tested negative for CDH1 pathogenic germline variants. A deleterious CTNNA1 germline variant was found in 0.7% (1/141) of diffuse gastric cancer patients meeting the 2020 IGCLC criteria, as compared to the rate of 2.8% of CDH1 deleterious variants found by us in this setting. No deleterious variants were found in CTNND1, but six variants of uncertain significance were identified in this gene. We did not find any pathogenic CDH1, CTNNA1 or CTNND1 variant in index patients with early-onset/familial mixed gastric cancer, so there is no evidence that supports including this tumor type in the testing criteria for germline variants in these genes. The role of the CTNND1 gene in inherited gastric cancer predisposition is still unclear.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15174313
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 9
    Online Resource
    Online Resource
    Aminodi(hetero)arylamines in the Thieno[3,2-b]pyridine Series: Synthesis, Effects in Human Tumor Cells Growth, Cell Cycle Analysis, Apoptosis and Evaluation of Toxicity Using Non-Tumor Cells
    MDPI AG ; 2012
    In:  Molecules Vol. 17, No. 4 ( 2012-03-28), p. 3834-3843
    Details
    In: Molecules, MDPI AG, Vol. 17, No. 4 ( 2012-03-28), p. 3834-3843
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules17043834
    Language: English
    Publisher: MDPI AG
    Publication Date: 2012
    detail.hit.zdb_id: 2008644-1
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  • 10
    Online Resource
    Online Resource
    Using a Dual CRISPR/Cas9 Approach to Gain Insight into the Role of LRP1B in Glioblastoma
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 14 ( 2023-07-10), p. 11285-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 14 ( 2023-07-10), p. 11285-
    Abstract: LRP1B remains one of the most altered genes in cancer, although its relevance in cancer biology is still unclear. Recent advances in gene editing techniques, particularly CRISPR/Cas9 systems, offer new opportunities to evaluate the function of large genes, such as LRP1B. Using a dual sgRNA CRISPR/Cas9 gene editing approach, this study aimed to assess the impact of disrupting LRP1B in glioblastoma cell biology. Four sgRNAs were designed for the dual targeting of two LRP1B exons (1 and 85). The U87 glioblastoma (GB) cell line was transfected with CRISPR/Cas9 PX459 vectors. To assess LRP1B-gene-induced alterations and expression, PCR, Sanger DNA sequencing, and qRT-PCR were carried out. Three clones (clones B9, E6, and H7) were further evaluated. All clones presented altered cellular morphology, increased cellular and nuclear size, and changes in ploidy. Two clones (E6 and H7) showed a significant decrease in cell growth, both in vitro and in the in vivo CAM assay. Proteomic analysis of the clones’ secretome identified differentially expressed proteins that had not been previously associated with LRP1B alterations. This study demonstrates that the dual sgRNA CRISPR/Cas9 strategy can effectively edit LRP1B in GB cells, providing new insights into the impact of LRP1B deletions in GBM biology.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms241411285
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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