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  • 1
    Online Resource
    Online Resource
    Molecular and Biological Investigation of Isolated Marine Fungal Metabolites as Anticancer Agents: A Multi-Target Approach
    MDPI AG ; 2023
    In:  Metabolites Vol. 13, No. 2 ( 2023-01-21), p. 162-
    Details
    In: Metabolites, MDPI AG, Vol. 13, No. 2 ( 2023-01-21), p. 162-
    Abstract: Cancer is the leading cause of death globally, with an increasing number of cases being annually reported. Nature-derived metabolites have been widely studied for their potential programmed necrosis, cytotoxicity, and anti-proliferation leading to enrichment for the modern medicine, particularly within the last couple of decades. At a more rapid pace, the concept of multi-target agents has evolved from being an innovative approach into a regular drug development procedure for hampering the multi-fashioned pathophysiology and high-resistance nature of cancer cells. With the advent of the Red Sea Penicillium chrysogenum strain S003-isolated indole-based alkaloids, we thoroughly investigated the molecular aspects for three major metabolites: meleagrin (MEL), roquefortine C (ROC), and isoroquefortine C (ISO) against three cancer-associated biological targets Cdc-25A, PTP-1B, and c-Met kinase. The study presented, for the first time, the detailed molecular insights and near-physiological affinity for these marine indole alkaloids against the assign targets through molecular docking-coupled all-atom dynamic simulation analysis. Findings highlighted the superiority of MEL’s binding affinity/stability being quite in concordance with the in vitro anticancer activity profile conducted via sulforhodamine B bioassay on different cancerous cell lines reaching down to low micromolar or even nanomolar potencies. The advent of lengthy structural topologies via the metabolites’ extended tetracyclic cores and aromatic imidazole arm permitted multi-pocket accommodation addressing the selectivity concerns. Additionally, the presence decorating polar functionalities on the core hydrophobic tetracyclic ring contributed compound’s pharmacodynamic preferentiality. Introducing ionizable functionality with more lipophilic characters was highlighted to improve binding affinities which was also in concordance with the conducted drug-likeness/pharmacokinetic profiling for obtaining a balanced pharmacokinetic/dynamic profile. Our study adds to the knowledge regarding drug development and optimization of marine-isolated indole-based alkaloids for future iterative synthesis and pre-clinical investigations as multi-target anticancer agents.
    Type of Medium: Online Resource
    ISSN: 2218-1989
    URL: Article
    DOI: 10.3390/metabo13020162
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662251-8
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  • 2
    Online Resource
    Online Resource
    Antibacterial, Antifungal, and Anticancer Effects of Camel Milk Exosomes: An In Vitro Study
    MDPI AG ; 2023
    In:  Veterinary Sciences Vol. 10, No. 2 ( 2023-02-06), p. 124-
    Details
    In: Veterinary Sciences, MDPI AG, Vol. 10, No. 2 ( 2023-02-06), p. 124-
    Abstract: Camel milk (CM) has potent antibacterial and antifungal effects and camel milk exosomes (CM-EXO) have been shown to inhibit the proliferation of a large variety of cancer cells including HepaRG, MCF7, Hl60, and PANC1. However, little is known regarding the effects of CM-EXO on bacteria, fungi, HepG2, CaCo2, and Vero cells. Therefore, this study aimed to evaluate the antibacterial, antifungal, and anticancer effects of CM-EXO. EXOs were isolated from CM by ultracentrifugation and characterized by transmission electron microscope and flow cytometry. Unlike CM, CM-EXO (6 mg/mL) had no bactericidal effects on Gram-positive bacteria (Staphylococcus aureus, Micrococcus luteus, and Enterococcus feacalis) but they had bacteriostatic effects, especially against Gram-negative strains (Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis), and fungistatic effects on Candida albicans. HepG2, CaCo2, and Vero cells were respectively treated with CM-EXOs at low (6.17, 3.60, 75.35 μg/mL), moderate (12.34, 7.20, 150.70 μg/mL), and high (24.68, 14.40, 301.40 μg/mL) doses and the results revealed that CM-EXOs triggered apoptosis in HepG2 and CaCo2 cells, but not in normal Vero cells, as revealed by high Bax expression and caspase 3 activities and lower expression of Bcl2. Interestingly, CM-EXOs also induced the elevation of intracellular reactive oxygen species and downregulated the expression of antioxidant-related genes (NrF2 and HO-1) in cancer cells but not in normal cells. CM-EXOs have antibacterial and antifungal effects as well as a selective anticancer effect against HepG2 and CaCo2 cells with a higher safety margin on normal cells.
    Type of Medium: Online Resource
    ISSN: 2306-7381
    URL: Article
    DOI: 10.3390/vetsci10020124
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2768971-2
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  • 3
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    Online Resource
    Anticancer Effects of New Ceramides Isolated from the Red Sea Red Algae Hypnea musciformis in a Model of Ehrlich Ascites Carcinoma: LC-HRMS Analysis Profile and Molecular Modeling
    MDPI AG ; 2022
    In:  Marine Drugs Vol. 20, No. 1 ( 2022-01-10), p. 63-
    Details
    In: Marine Drugs, MDPI AG, Vol. 20, No. 1 ( 2022-01-10), p. 63-
    Abstract: Different classes of phytochemicals were previously isolated from the Red Sea algae Hypnea musciformis as sterols, ketosteroids, fatty acids, and terpenoids. Herein, we report the isolation of three fatty acids—docosanoic acid 4, hexadecenoic acid 5, and alpha hydroxy octadecanoic acid 6—as well as three ceramides—A (1), B (2), and C (3)—with 9-methyl-sphinga-4,8-dienes and phytosphingosine bases. Additionally, different phytochemicals were determined using the liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (LC-ESI-HRMS) technique. Ceramides A (1) and B (2) exhibited promising in vitro cytotoxic activity against the human breast adenocarcinoma (MCF-7) cell line when compared with doxorubicin as a positive control. Further in vivo study and biochemical estimation in a mouse model of Ehrlich ascites carcinoma (EAC) revealed that both ceramides A (1) and B (2) at doses of 1 and 2 mg/kg, respectively, significantly decreased the tumor size in mice inoculated with EAC cells. The higher dose (2 mg/kg) of ceramide B (2) particularly expressed the most pronounced decrease in serum levels of vascular endothelial growth factor -B (VEGF-B) and tumor necrosis factor-α (TNF-α) markers, as well as the expression levels of the growth factor midkine in tumor tissue relative to the EAC control group. The highest expression of apoptotic factors, p53, Bax, and caspase 3 was observed in the same group that received 2 mg/kg of ceramide B (2). Molecular docking simulations suggested that ceramides A (1) and B (2) could bind in the deep grove between the H2 helix and the Ser240-P250 loop of p53, preventing its interaction with MDM2 and leading to its accumulation. In conclusion, this study reports the cytotoxic, apoptotic, and antiangiogenic effects of ceramides isolated from the Red Sea algae Hypnea musciformis in an experimental model of EAC.
    Type of Medium: Online Resource
    ISSN: 1660-3397
    URL: Article
    DOI: 10.3390/md20010063
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2175190-0
    SSG: 15,3
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  • 4
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    Online Resource
    Seasonal Changes in the Biochemical Composition of Dominant Macroalgal Species along the Egyptian Red Sea Shore
    MDPI AG ; 2023
    In:  Biology Vol. 12, No. 3 ( 2023-03-07), p. 411-
    Details
    In: Biology, MDPI AG, Vol. 12, No. 3 ( 2023-03-07), p. 411-
    Abstract: Macroalgae are significant biological resources in coastal marine ecosystems. Seasonality influences macroalgae biochemical characteristics, which consequentially affect their ecological and economic values. Here, macroalgae were surveyed from summer 2017 to spring 2018 at three sites at 7 km (south) from El Qusier, 52 km (north) from Marsa Alam and 70 km (south) from Safaga along the Red Sea coast, Egypt. Across all the macroalgae collected, Caulerpa prolifera (green macroalgae), Acanthophora spicifera (red macroalgae) and Cystoseira myrica, Cystoseira trinodis and Turbinaria ornata (brown macroalgae) were the most dominant macroalgal species. These macroalgae were identified at morphological and molecular (18s rRNA) levels. Then, the seasonal variations in macroalgal minerals and biochemical composition were quantified to determine the apt period for harvesting based on the nutritional requirements for commercial utilizations. The chemical composition of macroalgae proved the species and seasonal variation. For instance, minerals were more accumulated in macroalgae C. prolifera, A. spicifera and T. ornata in the winter season, but they were accumulated in both C. myrica and C. trinodis in the summer season. Total sugars, amino acids, fatty acids and phenolic contents were higher in the summer season. Accordingly, macroalgae collected during the summer can be used as food and animal feed. Overall, we suggest the harvesting of macroalgae for different nutrients and metabolites in the respective seasons.
    Type of Medium: Online Resource
    ISSN: 2079-7737
    URL: Article
    DOI: 10.3390/biology12030411
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2661517-4
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  • 5
    Online Resource
    Online Resource
    Integration of Chemoinformatics and Multi-Omics Analysis Defines ECT2 as a Potential Target for Cancer Drug Therapy
    MDPI AG ; 2023
    In:  Biology Vol. 12, No. 4 ( 2023-04-18), p. 613-
    Details
    In: Biology, MDPI AG, Vol. 12, No. 4 ( 2023-04-18), p. 613-
    Abstract: Epithelial cell transforming 2 (ECT2) is a potential oncogene and a number of recent studies have correlated it with the progression of several human cancers. Despite this elevated attention for ECT2 in oncology-related reports, there is no collective study to combine and integrate the expression and oncogenic behavior of ECT2 in a panel of human cancers. The current study started with a differential expression analysis of ECT2 in cancerous versus normal tissue. Following that, the study asked for the correlation between ECT2 upregulation and tumor stage, grade, and metastasis, along with its effect on patient survival. Moreover, the methylation and phosphorylation status of ECT2 in tumor versus normal tissue was assessed, in addition to the investigation of the ECT2 effect on the immune cell infiltration in the tumor microenvironment. The current study revealed that ECT2 was upregulated as mRNA and protein levels in a list of human tumors, a feature that allowed for the increased filtration of myeloid-derived suppressor cells (MDSC) and decreased the level of natural killer T (NKT) cells, which ultimately led to a poor prognosis survival. Lastly, we screened for several drugs that could inhibit ECT2 and act as antitumor agents. Collectively, this study nominated ECT2 as a prognostic and immunological biomarker, with reported inhibitors that represent potential antitumor drugs.
    Type of Medium: Online Resource
    ISSN: 2079-7737
    URL: Article
    DOI: 10.3390/biology12040613
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2661517-4
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  • 6
    Online Resource
    Online Resource
    Exploring Exogenous Indole-3-acetic Acid’s Effect on the Growth and Biochemical Profiles of Synechocystis sp. PAK13 and Chlorella variabilis
    MDPI AG ; 2023
    In:  Molecules Vol. 28, No. 14 ( 2023-07-19), p. 5501-
    Details
    In: Molecules, MDPI AG, Vol. 28, No. 14 ( 2023-07-19), p. 5501-
    Abstract: Microalgae have garnered scientific interest for their potential to produce bioactive compounds. However, the large-scale industrial utilization of microalgae faces challenges related to production costs and achieving optimal growth conditions. Thus, this study aimed to investigate the potential role of exogenous indole-3-acetic acid (IAA) application in improving the growth and production of bioactive metabolites in microalgae. To this end, the study employed different concentrations of exogenously administered IAA ranging from 0.36 µM to 5.69 µM to assess its influence on the growth and biochemical composition of Synechocystis and Chlorella. IAA exposure significantly increased IAA levels in both strains. Consequentially, improved biomass accumulation in parallel with increased total pigment content by approximately eleven-fold in both strains was observed. Furthermore, the application of IAA stimulated the accumulation of primary metabolites. Sugar levels were augmented, providing a carbon source that facilitated amino acid and fatty acid biosynthesis. As a result, amino acid levels were enhanced as well, leading to a 1.55-fold increase in total amino acid content in Synechocystis and a 1.42-fold increase in Chlorella. Total fatty acids content increased by 1.92-fold in Synechocystis and by 2.16-fold in Chlorella. Overall, the study demonstrated the effectiveness of exogenously adding IAA as a strategy for enhancing the accumulation of microalgae biomass and biomolecules. These findings contribute to the advancement of microalgae-based technologies, opening new avenues to produce economically important compounds derived from microalgae.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules28145501
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2008644-1
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  • 7
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    Online Resource
    Ameliorative Effects of Camel Milk and Its Exosomes on Diabetic Nephropathy in Rats
    MDPI AG ; 2022
    In:  Membranes Vol. 12, No. 11 ( 2022-10-28), p. 1060-
    Details
    In: Membranes, MDPI AG, Vol. 12, No. 11 ( 2022-10-28), p. 1060-
    Abstract: Contradictory results were obtained regarding the effects of extracellular vesicles such as exosomes (EXOs) on diabetes and diabetic nephropathy (DN). Some studies showed that EXOs, including milk EXOs, were involved in the pathogenesis of DN, whereas other studies revealed ameliorative effects. Compared to other animals, camel milk had unique components that lower blood glucose levels. However, little is known regarding the effect of camel milk and its EXOs on DN. Thus, the present study was conducted to evaluate this effect on a rat model of DN induced by streptozotocin. Treatment with camel milk and/or its EXOs ameliorated DN as evidenced by (1) reduced levels of kidney function parameters (urea, creatinine, retinol-binding protein (RBP), and urinary proteins), (2) restored redox balance (decreased lipid peroxide malondialdehyde (MDA) and increased the activity of antioxidants enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)), (3) downregulated expression of DN-related genes (transforming growth factor-beta 1 (TGFβ1), intercellular adhesion molecules 1 (ICAM1), and transformation specific 1 (ETS1), integrin subunit beta 2 (ITGβ2), tissue inhibitors of matrix metalloproteinase 2 (TIMP2), and kidney injury molecule-1 (KIM1)), and (4) decreased renal damage histological score. These results concluded that the treatment with camel milk and/or its EXOs could ameliorate DN with a better effect for the combined therapy.
    Type of Medium: Online Resource
    ISSN: 2077-0375
    URL: Article
    DOI: 10.3390/membranes12111060
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2614641-1
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