New Pim-1 Kinase Inhibitor From the Co-culture of Two Sponge-Associated Actinomycetes

Saccharomonospora sp. UR22 and Dietzia sp. UR66, two actinomycetes derived from the Red Sea sponge Callyspongia siphonella, were co-cultured and the induced metabolites were monitored by HPLC-DAD and TLC. Saccharomonosporine A (1), a novel brominated oxo-indole alkaloid, convolutamydine F (2) along with other three known induced metabolites (3-5) were isolated from the EtOAc extract of Saccharomonospora sp. UR22 and Dietzia sp. UR66 co-culture. Additionally, axenic culture of Saccharomonospora sp. UR22 led to isolation of six known microbial metabolites (6-11). A kinase inhibition assay results showed that compounds 1 and 3 were potent Pim-1 kinase inhibitors with an IC50 value of 0.3 ± 0.02 and 0.95 ± 0.01 μM, respectively. Docking studies revealed the binding mode of compounds 1 and 3 in the ATP pocket of Pim-1 kinase. Testing of compounds 1 and 3 displayed significant antiproliferative activity against the human colon adenocarcinoma HT-29, (IC50 3.6 and 3.7 μM, respectively) and the human promyelocytic leukemia HL-60, (IC50 2.8 and 4.2 μM, respectively). These results suggested that compounds 1 and 3 act as potential Pim-1 kinase inhibitors that mediate the tumor cell growth inhibitory effect. This study highlighted the co-cultivation approach as an effective strategy to increase the chemical diversity of the secondary metabolites hidden in the genomes of the marine actinomycetes

Untargeted Metabolomic Profiling and Antioxidant Capacities of Different Solvent Crude Extracts of Ephedra foeminea

Ephedra foeminea is a traditional medicinal plant used in the Eastern Mediterranean region. This study aims to investigate the chemical profiles of different solvent extracts of E. foeminea via an untargeted metabolomics approach, alongside determining their antioxidant capacities. E. foeminea samples collected from Jordan were macerated in solvents of varying polarities; dichloromethane/methanol, methanol, ethanol, ethyl acetate, and acetone. The crude extracts were subjected to comprehensive chemical profiling and metabolomics study using Gas chromatography–Mass spectrometry (GC–MS), Liquid chromatography–Mass spectrometry (LC–MS), and Nuclear Magnetic Resonance (NMR). The obtained data were analyzed using Venn diagrams, Principle Component Analysis (PCA), and Metabolite Enrichment Set Analysis (MESA). ABTS assay was performed to measure the crude extracts’ antioxidant activity. MESA revealed the dominant chemical groups as amino acids, fatty acids, carboxylic acids, and carbohydrates. Results indicated that dichloromethane/methanol and methanolic extracts had the most distinct composition as well as the most unique compounds. The methanolic extract had the most potency (IC50 249.6 µg/mL) in the ABTS assay. However, no significant differences were found. In conclusion, solvents influenced the recovery of metabolites in E. foeminea and the antioxidant activity of the E. foeminea methanolic extract could be correlated to the abundant presence of diverse bioactive compounds

Fabrication of Hollow Nanocones Membrane with an Extraordinary Surface Area as CO₂ Sucker

Recently, more and more attention has been paid to the development of eco-friendly solid sorbents that are cost-effective, noncorrosive, have a high gas capacity, and have low renewable energy for CO2 capture. Here, we claimed the fabrication of a three-dimensional (3D) film of hollow nanocones with a large surface area (949.5 m2/g), a large contact angle of 136.3°, and high surface energy. The synthetic technique is based on an electrochemical polymerization process followed by a novel and simple strategy for pulling off the formed layers as a membrane. Although the polymer-coated substrates were reported previously, the membrane formation has not been reported elsewhere. The detachable capability of the manufactured layer as a membrane braked the previous boundaries and allows the membrane’s uses in a wide range of applications. This 3D hollow nanocones membrane offer advantages over conventional ones in that they combine a π-electron-rich (aromatic ring), hydrophobicity, a large surface area, multiple amino groups, and a large pore volume. These substantial features are vital for CO2 capturing and storage. Furthermore, the hydrophobicity characteristic and application of the formed polymer as a CO2 sucker were investigated. These results demonstrated the potential of the synthesized 3D hollow polymer to be used for CO2 capturing with a gas capacity of about 68 mg/g and regeneration ability without the need for heat up

Borderline ovarian tumors: a retrospective cohort study on single institution experience, practice patterns and outcomes

Borderline ovarian tumours (BOTs) commonly affect young nulliparous women, thus making fertility-preserving approaches more desirable. Women who opt for conservative management should be counselled about disease recurrence. In this retrospective study, the medical records of 57 women with BOT treated at the American University of Beirut Medical Centre between January 1986 and May 2018 were reviewed. Clinical, pathologic, and demographic data were collected and analysed to identify variables associated with poor clinical outcomes including advanced disease and risk of recurrence. Younger and nulliparous women were more likely to undergo fertility-sparing surgery. The open approach was adopted for women with larger adnexal masses and was associated with more blood loss with a mean difference of 172 mL (95% CI [110–235], p-value < .001) but no significant difference in operative time and length of hospital stay compared to the laparoscopic approach. CA-125 correlated with an advanced International Federation of Gynaecology and Obstetrics (FIGO) stage (p = .004). The recurrence rate was found to be 7% with a median recurrence time of 41.5 months.IMPACT STATEMENT What is already known on this subject? BOTs are common in young nulliparous women who often desire fertility-sparing procedures. Prognostic factors associated with disease severity and recurrence remain controversial. What do the results of this study add? This study presents an opportunity to understand the disease behaviour and compare local practices and outcomes to what was reported in the literature. CA-125 appears to be a useful marker in predicting the stage of BOT. What are the implications of these findings for clinical practice and/or further research? Future research should focus on exploring whether BOTs with micropapillary features represent an aggressive histologic subtype more prone to recurrence

Anti-cancer agents in Saudi Arabian herbals revealed by automated high-content imaging

<div><p>Natural products have been used for medical applications since ancient times. Commonly, natural products are structurally complex chemical compounds that efficiently interact with their biological targets, making them useful drug candidates in cancer therapy. Here, we used cell-based phenotypic profiling and image-based high-content screening to study the mode of action and potential cellular targets of plants historically used in Saudi Arabia’s traditional medicine. We compared the cytological profiles of fractions taken from <i>Juniperus phoenicea</i> (Arar), <i>Anastatica hierochuntica</i> (Kaff Maryam), and <i>Citrullus colocynthis</i> (Hanzal) with a set of reference compounds with established modes of action. Cluster analyses of the cytological profiles of the tested compounds suggested that these plants contain possible topoisomerase inhibitors that could be effective in cancer treatment. Using histone H2AX phosphorylation as a marker for DNA damage, we discovered that some of the compounds induced double-strand DNA breaks. Furthermore, chemical analysis of the active fraction isolated from <i>Juniperus phoenicea</i> revealed possible anti-cancer compounds. Our results demonstrate the usefulness of cell-based phenotypic screening of natural products to reveal their biological activities.</p></div