Targeting STAT3 and NF-κB Signaling Pathways in Cancer Prevention and Treatment: The Role of Chalcones.

Chalcones are a type of natural flavonoid compound that have been found to possess promising anticancer properties. Studies have shown that chalcones can inhibit the growth and proliferation of cancer cells, induce apoptosis, and suppress tumor angiogenesis. In addition to their potential therapeutic applications, chalcones have also been studied for their chemopreventive effects, which involve reducing the risk of cancer development in healthy individuals. Overall, the anticancer properties of chalcones make them a promising area of research for developing new cancer treatments and preventative strategies. This review aims to provide a thorough overview of the central studies reported in the literature concerning cancer prevention and the treatment of chalcones. Although chalcones target many different mechanisms, the STAT and NF-κB signaling pathways are the ones this review will focus on, highlighting the existing crosstalk between these two pathways and considering the potential therapeutic opportunities for chalcone combinations.

PRI-724 and IWP-O1 Wnt Signaling Pathway Inhibitors Modulate the Expression of Glycolytic Enzymes in Tongue Cancer Cell Lines.

The dysregulation of energetic metabolism is one of the hallmarks of cancer cells. Indeed, the growth of head and neck squamous cell carcinoma (HNSCC) cells depends heavily on glycolytic activity, which can be considered a potential therapeutic target. Wnt signaling is one of the pathways that undergoes upregulation in HNSCC. Our previous studies have shown that Wnt signaling inhibitors-PRI-724 and IWP-O1-attenuate tongue SCC survival and reduce glucose uptake and lactate release. The aim of this research was to further evaluate the possible mechanisms of the previously observed effects. We assessed the effect of PRI-724 and IWP-O1 on the expression of selected glycolytic enzymes: phosphofructokinase M, pyruvate kinase M2, and lactate dehydrogenase. Relative transcript expression was assessed by real-time PCR, and protein levels by Western blot. Moreover, clinical data concerning mRNA and protein expression, gene promoter methylation, and HNSCC patients' survival time were analyzed by the UALCAN tool, and protein-protein interaction was assessed using the STRING database. Experimental and bioinformatic data confirmed the relation between Wnt signaling and glycolytic enzymes in tongue cancer cells and HNSCC clinical samples. Overall, the inhibition of glucose metabolism by Wnt signaling inhibitors is a promising mode of action against tongue cancer cells.

Resistance Inducers for the Protection of Pedunculate Oak (Quercus robur L.) Seedlings against Powdery Mildew Erysiphe alphitoides.

Oak powdery mildew caused by Erysiphe alphitoides (Griffon and Maubl.; U. Braun & S. Takam.) is a common disease in European forests. One of the most susceptible species is the pedunculate oak (Quercus robur L.). Presently, a few methods are available to control powdery mildew, e.g., the use of fungicides (e.g., based on citric acid), antagonistic fungi or bacteria, chemical treatments (e.g., sulphur, potassium bicarbonate) or genetic resistance. In our study, we aimed to check the effects of using chitosan derivatives and novel active substances inducing the plants' natural resistance: benzodiathiadiazole (both in neutral and salt form). 84 pedunculate oak seedlings were subjected to the experiment in three treatment variants (plus positive and negative controls). The plants were treated with active substances and inoculated with E. alphitoides. Although the powdery mildew symptoms appeared in all variants, they were manifested mainly by the mycelium in the form of small spots. The experiment indicated that the highest limitation of powdery mildew mycelium was achieved by applying N-methyl-N-methoxyamide-7-carboxybenzo(1,2,3)thiadiazole (BTHWA). The application of BTHWA reduced disease development by 88.9% when compared to the effects of the other variants.

Soil mycobiome in sustainable agriculture.

The soil microbiome contributes to several ecosystem processes. It plays a key role in sustainable agriculture, horticulture and forestry. In contrast to the vast number of studies focusing on soil bacteria, the amount of research concerning soil fungal communities is limited. This is despite the fact that fungi play a crucial role in the cycling of matter and energy on Earth. Fungi constitute a significant part of the pathobiome of plants. Moreover, many of them are indispensable to plant health. This group includes mycorrhizal fungi, superparasites of pathogens, and generalists; they stabilize the soil mycobiome and play a key role in biogeochemical cycles. Several fungal species also contribute to soil bioremediation through their uptake of high amounts of contaminants from the environment. Moreover, fungal mycelia stretch below the ground like blood vessels in the human body, transferring water and nutrients to and from various plants. Recent advances in high-throughput sequencing combined with bioinformatic tools have facilitated detailed studies of the soil mycobiome. This review discusses the beneficial effects of soil mycobiomes and their interactions with other microbes and hosts in both healthy and unhealthy ecosystems. It may be argued that studying the soil mycobiome in such a fashion is an essential step in promoting sustainable and regenerative agriculture.

Olea europaea L. Root Endophyte Bacillus velezensis OEE1 Counteracts Oomycete and Fungal Harmful Pathogens and Harbours a Large Repertoire of Secreted and Volatile Metabolites and Beneficial Functional Genes.

Oomycete and fungal pathogens, mainly Phytophthora and Fusarium species, are notorious causal agents of huge economic losses and environmental damages. For instance, Phytophthora ramorum, Phytophthora cryptogea, Phytophthora plurivora and Fusarium solani cause significant losses in nurseries and in forest ecosystems. Chemical treatments, while harmful to the environment and human health, have been proved to have little or no impact on these species. Recently, biocontrol bacterial species were used to cope with these pathogens and have shown promising prospects towards sustainable and eco-friendly agricultural practices. Olive trees prone to Phytophthora and Fusarium disease outbreaks are suitable for habitat-adapted symbiotic strategies, to recover oomycetes and fungal pathogen biocontrol agents. Using this strategy, we showed that olive trees-associated microbiome represents a valuable source for microorganisms, promoting plant growth and healthy benefits in addition to being biocontrol agents against oomycete and fungal diseases. Isolation, characterization and screening of root microbiome of olive trees against numerous Phytophthora and other fungal pathogens have led to the identification of the Bacillus velezensis OEE1, with plant growth promotion (PGP) abilities and strong activity against major oomycete and fungal pathogens. Phylogenomic analysis of the strain OEE1 showed that B. velezensis suffers taxonomic imprecision that blurs species delimitation, impacting their biofertilizers' practical use. Genome mining of several B. velezensis strains available in the GenBank have highlighted a wide array of plant growth promoting rhizobacteria (PGPR) features, metals and antibiotics resistance and the degradation ability of phytotoxic aromatic compounds. Strain OEE1 harbours a large repertoire of secreted and volatile secondary metabolites. Rarefaction analysis of secondary metabolites richness in the B. velezenis genomes, unambiguously documented new secondary metabolites from ongoing genome sequencing efforts that warrants more efforts in order to assess the huge diversity in the species. Comparative genomics indicated that B. velezensis harbours a core genome endowed with PGP features and accessory genome encoding diverse secondary metabolites. Gas Chromatography-Mass Spectrometry (GC-MS) analysis of OEE1 Volatile Organic Compounds (VOCs) and Liquid Chromatography High Resolution Mas Spectrometry (LC-HRMS) analysis of secondary metabolites identified numerous molecules with PGP abilities that are known to interfere with pathogen development. Moreover, B. velezensis OEE1 proved effective in protecting olive trees against F. solani in greenhouse experiments and are able to inhabit olive tree roots. Our strategy provides an effective means for isolation of biocontrol agents against recalcitrant pathogens. Their genomic analysis provides necessary clues towards their efficient implementation as biofertilizers.

Fungal Biodiversity and Their Role in Soil Health.

Soil health, and the closely related terms of soil quality and fertility, is considered as one of the most important characteristics of soil ecosystems. The integrated approach to soil health assumes that soil is a living system and soil health results from the interaction between different processes and properties, with a strong effect on the activity of soil microbiota. All soils can be described using physical, chemical, and biological properties, but adaptation to environmental changes, driven by the processes of natural selection, are unique to the latter one. This mini review focuses on fungal biodiversity and its role in the health of managed soils as well as on the current methods used in soil mycobiome identification and utilization next generation sequencing (NGS) approaches. The authors separately focus on agriculture and horticulture as well as grassland and forest ecosystems. Moreover, this mini review describes the effect of land-use on the biodiversity and succession of fungi. In conclusion, the authors recommend a shift from cataloging fungal species in different soil ecosystems toward a more global analysis based on functions and interactions between organisms.

Strain-level diversity of secondary metabolism in the biocontrol species Aneurinibacillus migulanus.

Aneurinibacillus migulanus strains Nagano and NCTC 7096 show potential in biocontrol against fungal and fungus-like plant pathogens, including a wide range of Ascomycota, Basidiomycota, and Oomycetes. Differences in terms of the range of pathogens that each strain inhibits, however, suggested that production of a single antibiotic cyclic peptide, gramicidin S (GS), by the two strains, is not the sole mechanism of inhibition. The availability of four sequenced genomes of Aneurinibacillus prompted us to apply genome mining techniques to identify the bioactive potential of A. migulanus and to provide insights into the secondary metabolite arsenal of the genus Aneurinibacillus. Up to eleven secondary metabolite biosynthetic gene clusters were present in the three Aneurinibacillus species. Biosynthetic gene clusters specifying bacteriocins, microcins, non-ribosomal peptides, polyketides, terpenes, phosphonates, lasso peptides and linaridins were identified. Chitinolytic potential and iron metabolism regulation were also investigated. With increasing numbers of biocontrol bacterial genomes being sequenced and mined, the use of approaches similar to those described in this paper will lead to an increase in the numbers of environmentally friendly natural products available to use against plant diseases.