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The red palm weevil (RPW), Rhynchophorus ferrugineus, poses a significant threat to date palms globally, heavily relying on symbiotic microbes for various physiological and behavioral functions. This comprehensive study delves into the intricate dynamics of RPW gut microbiota, revealing a diverse microbial community consisting of seven genera and eight species from Proteobacteria, Firmicutes, and Actinobacteria. The stability of gut bacteria across different life stages was observed, with notable impacts on larval metabolism attributed to shifts in bacterial composition. Bacillus subtilis emerged as a key player, producing a spectrum of metabolic enzymes. Furthermore, the gut bacteria exhibited remarkable pesticide degradation capabilities, suggesting a potential role in the host's resistance to pesticides. The Arthrobacter sp. was identified as a promising candidate for eco-friendly pest biocontrol and biodegradation strategies. Investigating the influence of thermal stress on two groups of RPW larvae (conventional-fed and antibiotic-fed) at varying temperatures (15, 27, and 35 °C) unveiled potential survival implications. This study highlights the pivotal role of bacterial symbionts in enabling larvae adaptation and thermal stress tolerance. In essence, this research contributes crucial insights into the diversity and functions of RPW gut bacteria, emphasizing their prospective applications in pest control strategies. [ABSTRACT FROM AUTHOR]

Root knot nematode (RKN), Meloidogyne incognita, is considered a major soil-borne pathogen that can cause severe yield losses for vegetables and diverse crops. Usually, reducing of M. incognita damage is mainly relies on the application of nematicides and good agricultural practices. However, the use of synthetic nematicides is restricted due to concerns about their impact on the environment and human health. As a result, the use of alternative strategies is becoming necessary to combat RKN resistance. This study evaluates the antagonistic impact of the root mutualistic fungus Piriformospora indica on M. incognita. It also assesses its influence on the nutritional status, photo-synthesis, antioxidant enzyme activity, endogenous abscisic acid (ABA) levels, and selected ABA related-responsive genes in cucumber plants. Roots of cucumber seedlings were inoculated with P. indica and the second-stage juveniles (1000 J2 per plant). The results demonstrated that P. indica significantly reduced M. incognita invasion in roots, resulting in a 24% reduction in root galling and 42.6% decline in final population. Inoculating plants with both P. indica and RKN increased performance of root fresh and dry weight, as well as improved photochemical efficiency of PSII (Fv/Fm), photosystem II efficiency (PSII), catalase (CAT), peroxidase (POD), and superoxide dis-mutase (SOD). Furthermore, P. indica colonization, either alone or in combination with M. incognita, significantly improved number of fruits per plant, average fruit weight, the plant's marketable yield, and leaf nutrient content (N, P, K and Mg), Moreover, there was an increase in IAA content combined with a decrease in ABA content in roots of dual inoculation plants, if compared to M. incognita infested plants. The highest ABA content was recorded in the root of RKN-cucumber plants. The decline in ABA content due to P. indica treatment was consistent with the modulation of ABA pathway genes, specifically PP2C, PYL1, RK2,1, and RK2,2. The mixed of P. indica and M. incognita led to a decrease in the expression of PP2C, PLY1, RK2,1, and RK2,2 in comparison to the control group. These results indicate that P. indica application could help reduce the negative effects of RKN on important crops. [ABSTRACT FROM AUTHOR]

The Red Sea soft coral Sarcophyton acutum ethyl acetate extract has afforded one new cembranoid; sarcacutumolid A (1), along with six known metabolites have been isolated from S. acutum for the first time (2-7). Chemical structures were elucidated by employing several spectroscopic analyses. The cytotoxic potential of the isolated compounds was assessed against four human cancer cell lines; hepatocellular (HepG2), cervical (HeLa), breast (MCF-7) and colorectal cancer (Colo-205). Sarcacutumolid A (1) and gorgosterol (7) inhibited colorectal cancer cell proliferation in a concentration-dependent manner with IC50 values of 35.5 and 44.0 μM, respectively. [ABSTRACT FROM AUTHOR]

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ABCG2 is a substantial member of the ABC transporter superfamily that plays a significant role in multidrug resistance in cancer. Until recently, the 3D structure of ABCG2 has not been resolved, which resulted in the limitation of developing potential ABCG2 inhibitors using structure‐based drug discovery. Herein, eMolecules, ChEMBL, and ChEBI databases, containing >25 million compounds, were virtually screened against the ABCG2 transporter in homodimer form. Performance of AutoDock4.2.6 software to predict inhibitor‐ABCG2 binding mode and affinity were validated on the basis of available experimental data. The explored databases were filtered based on docking scores. The most potent hits with binding affinities higher than that of experimental bound ligand (MZ29) were then selected and subjected to molecular mechanics minimization, followed by binding energy calculation using molecular mechanics‐generalized Born surface area (MM‐GBSA) approach. Furthermore, molecular dynamics simulations for 50 ns, followed by MM‐GBSA binding energy calculations, were performed for the promising compounds, unveiling eight potential inhibitors with binding affinities <−55.8 kcal/mol. Structural and energetic analyses demonstrated the stability of the eight identified inhibitors over the 50 ns MD simulation. This research sheds light on the potentiality of the identified ABCG2 inhibitors as a therapeutic approach to overcome multidrug resistance cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Leukemia is one of the most lethal cancers worldwide and represents the sixth-leading cause of cancer deaths. The results of leukemia treatment have not been as positive as desired, and recurrence is common., Purpose: Thus, there is an urgent requirement for the development of new therapeutic drugs. Salvia multicaulis (Bardakosh) is a widespread species that contains multiple phytochemical components with anti-cancer activities., Methods: We isolated and characterized the major diterpene candesalvone B methyl ester from S. multicaulis and investigated its action as a cytotoxic agent towards sensitive and drug-resistant leukemia cells by the resazurin reduction assay. Additionally, the targeted genes and the affected molecular mechanisms attributed to the potent cytotoxic activities were discovered by transcriptome-wide mRNA expression profiling. The targets predicted to be regulated by candesalvone B methyl ester in each cell line were confirmed by qRT-PCR, molecular docking, microscale thermophoresis, and western blotting. Moreover, cell cycle distribution and apoptosis were analyzed by flow cytometry., Results: Candesalvone B methyl ester was cytotoxic with IC 50 values of 20.95 ± 0.15 µM against CCRF-CEM cells and 4.13 ± 0.10 µM against multidrug-resistant CEM/ADR5000 leukemia cells. The pathway enrichment analysis disclosed that candesalvone B methyl ester could regulate the heat-shock response signaling pathway via targeting heat shock factor 1 (HSF1) in CCRF-CEM cells and ELOVL fatty acid elongase 5 (ELOVL5) controls the fatty acid metabolism pathway in CEM/ADR5000 cells. Microscale thermophoresis showed the binding of candesalvone B methyl ester with HSF1 and ELOVL5, confirming the results of molecular docking analysis. Down-regulation of both HSF1 and ELOVL5 by candesalvone B methyl ester as detected by both western blotting and RT-qPCR was related to the reversal of drug resistance in the leukemia cells. Furthermore, candesalvone B methyl ester increased the arrest in the sub-G1 phase of the cell cycle in a dose-dependent manner from 1.3 % to 32.3 % with concomitant induction of apoptosis up to 29.0 % in CCRF-CEM leukemic cells upon inhibition of HSF1., Conclusion: Candesalvone B methyl ester isolated from S. multicaulis exerted cytotoxicity by affecting apoptosis, cell division, and modulation of expression levels of genes contributing to the heat stress signaling and fatty acid metabolism pathways that could relieve drug resistance of leukemia cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)