Chrysophanol inhibits of colorectal cancer cell motility and energy metabolism by targeting the KITENIN/ErbB4 oncogenic complex.

BACKGROUND: Expression of the KITENIN/ErbB4 oncogenic complex is associated with metastasis of colorectal cancer to distant organs and lymph nodes and is linked with poor prognosis and poor survival. METHODS: Here, we used in vitro and in silico methods to test the ability of chrysophanol, a molecule of natural origin, to suppress the progression of colorectal cancer by targeting the KITENIN/ErbB4 complex. RESULTS: Chrysophanol binds to ErbB4, disrupting the ErbB4/KITENIN complex and causing autophagic degradation of KITENIN. We demonstrated that chrysophanol binds to ErbB4 according to a molecular docking model. Chrysophanol reversed KITENIN-mediated effects on cell motility, aerobic glycolysis, and expression of downstream effector genes. Moreover, under conditions of KITENIN overexpression, chrysophanol suppressed the production of onco-metabolites. CONCLUSION: Chrysophanol suppresses oncogenic activities by targeting the KITENIN/ErbB4 complex.

Could insects be an alternative food source? A comprehensive review.

According to the United Nations, more than 800 million people are exposed to starvation. It is predicted that the world population will face much more serious starvation for reasons such as global warming, diseases, economic problems, rapid urbanization, and destruction of agricultural areas and water resources. Thus, there are significant hesitations about the sustainability of food resources, and the search for alternative food sources has increased. One of the leading alternative food sources is insects. Although the use of edible insects has been accepted in some areas of the world, entomophagy is not preferred in some countries due to sociocultural conditions, health concerns, neophobia, and entomophobia. Many people do not accept the direct consumption of raw insects, but insects can be transformed into more preferred forms by using different cooking techniques. Some ground edible insects are satisfactory in terms of nutritional value and have a reasonable level of acceptability when added to products such as bread, tortilla, and pasta in varying percentages. The world market value of edible insects was estimated to be US$3.2 million in 2021 and US$17.6 billion in 2032. In this review, the current and future situation of insects as an alternative food source is comprehensively discussed.

A fatty acid-rich fraction of an endolichenic fungus Phoma sp. suppresses immune checkpoint markers via AhR/ARNT and ESR1.

Lung cancer has the highest mortality rates worldwide. The disease is caused by environmental pollutants, smoking, and many other factors. Recent treatments include immunotherapeutics, which have shown some success; however, the search for new therapeutics is ongoing. Endolichenic fungi produce a whale of a lot of secondary metabolites, the therapeutic effects of which are being evaluated. Here, we used a crude extract and subfractions of the endolichenic fungus, Phoma sp. (EL006848), isolated from the Pseudevernia furfuracea. It was identified the fatty acid components, palmitic acid, stearic acid, and oleic acid, exist in subfractions E1 and E2. In addition, EL006848 and its fatty acids fractions suppressed benzo[a]pyrene (an AhR ligand)- induced expression of PD-L1 to inhibit the activity of multiple immune checkpoints. E2 subfraction, which had a higher fatty acid content than E1, downregulated expression of AhR/ARNT and several human transcription factors related to ESR1. Moreover, E2 showed a strong inhibitory effect on STAT3 expression and mild effect on NF-kB activity. These results suggest that fatty acids extracted from an endolichenic fungus can exert strong immunotherapeutic effects.

Using proteomics, q-PCR and biochemical methods complementing as a multiapproach to elicit the crucial responses of zebrafish liver exposed to neonicotinoid pesticide.

Pesticides enter the environment through runoff and leaching and this raises public concern about effects on non-target organisms. Imidacloprid (IMI) a synthetic pesticide, has an unstable half-life, metabolized in minutes to weeks in the water. To evaluate the effects of IMI on the zebrafish liver, we conducted proteomic, molecular and biochemical analysis in a multi-level approach, to highlight the complementary features regarding the results of each method. Adult zebrafish were exposed to 60 mg/L IMI for 48 h and were evaluated using nLC-MS/MS for proteins, q-PCR analysis for expression of cat, gpx, pxr, ache, along with CAT and AChE enzyme activities and GSH and MDA assays. Based on proteomics, the regulation of antioxidant and immune responses, as well as gene transcription were significant processes affected. Apoptosis and ER stress pathways were upregulated and there was a down-regulation of cat and gpx genes. There was also elevated CAT activity and GSH and decreased MDA. Additionally, elevated AChE activity and up regulation of ache expression was observed. The multi-approach results included regulators of antioxidant, xenobiotic response and neuro-protective related proteins (genes and enzymes), which overall reflected harmful effects of IMI. Consequently, this study highlights the effects of IMI on zebrafish liver and reveals new potential biomarkers. In this respect, evaluated outcomes reveal the complementary features emphasizing the importance of studying chemicals using several methods. Our study provides deeper insights for future work in ecotoxicological studies regarding IMI and contribute to existing toxicity literature.

Effects of UV-B Radiation on the Performance, Antioxidant Response and Protective Compounds of Hazelnut Pollen.

Increasing ultraviolet (UV) radiation is expected to become a problem in hazelnut cultivation. The aim of this study is to examine the effects of UV-B on hazelnut pollen. To this end, the pollens were exposed to UV-B for 1, 2, and 3 h at distances of 10, 20, 30, and 40 cm. Groups treated for 2 h at 20 cm and 3 h at 10 and 20 cm were identified as the most affected based on the results of viability, germination, and tube elongation. Further studies on these groups showed that UV-B does not change the DPPH radical scavenging activity for all groups. However, total phenolic compounds decreased after 3 h of treatment at 10 and 20 cm, while total flavonoid compounds decreased after all treatment groups. The UV-B absorbance of cytoplasmic and cell-wall-bound fractions decreased for all groups. The UV-B absorbance of the sporopollenin-derived fraction increased after 2 h of treatment at 20 cm but decreases after treatment for 3 h at 10 and 20 cm. In summary, exposure to UV-B for different times and distances adversely affected pollen grains in terms of pollen viability, germination rate, tube length, and the level of antioxidant molecules and UV-absorbing compounds.

An acetonic extract and secondary metabolites from the endolichenic fungus Nemania sp. EL006872 exhibit immune checkpoint inhibitory activity in lung cancer cell.

Background: Endolichenic fungi (ELF), which live the inside the lichen thallus, contain many secondary metabolites that show various biological activities. Recent studies show that lichen and ELF secondary metabolites have antioxidant, antibacterial, antifungal, cytotoxic, and anticancer activities. Purpose: Here, the effects of an ELF extract and its bioactive compounds were investigated on the H1975 cell line focusing on immune checkpoint marker inhibition. Methods: An ELF was isolated from the host lichen Bryoria fuscescens (Gyelnik) Brodo and D. Hawksw and identified the species as Nemania sp. EL006872. The fungus was cultured on agar medium and acetonic extracts were obtained. Secondary metabolites radianspenes C and D, and dahliane D, were isolated from the crude extract. The biological effects of both the crude extract and the isolated secondary metabolites were evaluated in cell viability, qRT-PCR assays, flow cytometry analysis and western blotting. Results: The cell viability assay revealed that extracts from Nemania sp. EL006872 and the isolated secondary compounds had low cytotoxicity. The crude extract, radianspenes C and D, and dahliane D, suppressed expression of mRNA encoding PD-L1 and aromatic hydrocarbon receptor (AhR), and surface expression of PD-L1 protein by cells exposed to benzo[a] pyrene. Radianspenes C and D, and dahliane D, reduced expression of AhR, PD-L1, ICOSL, and GITRL proteins by H1975 lung cancer cells, as well as exerting anti-proliferative effects. Conclusion: Radianspenes C and D, and dahliane D, bioactive compounds isolated from Nemania sp. EL006872 ELF, have the potential for use as immunotherapy and immunoncology treatments.

Extremophilic Natrinema versiforme Against Pseudomonas aeruginosa Quorum Sensing and Biofilm.

Pseudomonas aeruginosa is an opportunistic pathogen that causes high morbidity and mortality rates due to its biofilm form. Biofilm formation is regulated via quorum sensing (QS) mechanism and provides up to 1000 times more resistance against conventional antibiotics. QS related genes are expressed according to bacterial population density via signal molecules. QS inhibitors (QSIs) from natural sources are widely studied evaluating various extracts from extreme environments. It is suggested that extremely halophilic Archaea may also produce QSI compounds. For this purpose, we tested QS inhibitory potentials of ethyl acetate extracts from cell free supernatants and cells of Natrinema versiforme against QS and biofilm formation of P. aeruginosa. To observe QS inhibition, all extracts were tested on P. aeruginosa lasB-gfp, rhlA-gfp, and pqsA-gfp biosensor strains and biofilm inhibition was studied using P. aeruginosa PAO1. According to our results, QS inhibition ratios of cell free supernatant extract (CFSE) were higher than cell extract (CE) on las system, whereas CE was more effective on rhl system. In addition, anti-biofilm effect of CFSE was higher than CE. Structural analysis revealed that the most abundant compound in the extracts was trans 4-(2-carboxy-vinyl) benzoic acid.

Reducing Virulence and Biofilm of Pseudomonas aeruginosa by Potential Quorum Sensing Inhibitor Carotenoid: Zeaxanthin.

Pseudomonas aeruginosa can regulate its virulence gene expressions by using a signal system called quorum sensing. It is known that inhibition of quorum sensing can block biofilm formation and leave the bacteria defenseless. Therefore, it is necessary to determine natural sources to obtain potential quorum sensing inhibitors. This study aims to investigate an alternative treatment approach by utilizing the carotenoid zeaxanthin to reduce the expressions of P. aeruginosa virulence factors through quorum sensing inhibition. The inhibition potential of zeaxanthin was determined by in silico screening from a library of 638 lichen metabolites. Fluorescent monitor strains were utilized for quorum sensing inhibitor screens, and quantitative reverse-transcriptase PCR assay was performed for evaluating gene expression. Results indicate that zeaxanthin is a better inhibitor than the lichen secondary metabolite evernic acid, which was previously shown to be capable of inhibiting P. aeruginosa quorum sensing systems.

Lichen secondary metabolite evernic acid as potential quorum sensing inhibitor against Pseudomonas aeruginosa.

Cystic Fibrosis is a genetic disease and it affects the respiratory and digestive systems. Pseudomonas aeruginosa infections in Cystic Fibrosis are presented as the main cause for high mortality and morbidity rates. Pseudomonas aeruginosa populations can regulate their virulence gene expressions via the bacterial communication system: quorum sensing. Inhibition of quorum sensing by employing quorum sensing inhibitors can leave the bacteria vulnerable. Therefore, determining natural sources to obtain potential quorum sensing inhibitors is essential. Lichens have ethnobotanical value for their medicinal properties and it is possible that their secondary metabolites have quorum sensing inhibitor properties. This study aims to investigate an alternative treatment approach by utilizing lichen secondary metabolite evernic acid to reduce the expressions of Pseudomonas aeruginosa virulence factors by inhibiting quorum sensing. For this purpose, fluorescent monitor strains were utilized for quorum sensing inhibitor screens and quantitative reverse-transcriptase PCR analyses were conducted for comparison. Results indicate that evernic acid is capable of inhibiting Pseudomonas aeruginosa quorum sensing systems.

Effects of Chlorine Stress on Pseudomonas aeruginosa Biofilm and Analysis of Related Gene Expressions.

Chlorine is deployed worldwide to clean waters and prevent water-originated illnesses. However, chlorine has a limited disinfection capacity against biofilms. Microorganisms form biofilms to protect themselves from biological threats such as disinfectant chemicals. Pseudomonas aeruginosa is an opportunistic pathogen and its biofilm form attaches to surfaces, living buried into exopolysaccharides, can be present in all watery environments including tap water and drinking water. This research aimed to study the biofilm trigger mechanism of the opportunistic pathogen P. aeruginosa PAO1 strain, which is known to form biofilm in water supply systems and human body, under chlorine stress levels. In addition to biofilm staining, certain genes that are relevant to the stress condition were selected for gene expression analysis. The bacteria cultures were grown under chlorine stress with concentrations of 0.5, 0.7 and 1 mg/l. Six gene regions were determined related to biofilm and stress response: rpoS, bifA, migA, katB, soxR, and algC. Biofilm formation was analyzed by basic fuchsin staining, and gene expressions were quantified by quantitative real-time PCR. According to the results, highest biofilm production was observed in P. aeruginosa PAO1 wild strain under no stress conditions. Higher biofilm amounts were observed for bacteria under 0.5 and 0.7 mg/l chlorine stress compared to 1 mg/l chlorine stress.

Inactivation of Escherichia coli and Staphylococcus aureus by ultrasound.

OBJECTIVES: The aim of this study was to obtain valuable information about the effect of ultrasonic irradiation with a frequency of 30 kHz frequency and power of 100 W on the inactivation capability of two bacterial groups, namely, Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923, in physiologic water samples. METHODS: Ultrasonic irradiation of bacterial samples with different populations of 5 × 10(3), 1.5 × 10(4), and 3 × 10(4) colony-forming units/mL was performed at a constant frequency with various treatment times. The specific energy (γ) values were calculated for these different concentrations of E coli and S aureus. The rate constant for ultrasonic inactivation was estimated in the linear region of a plot representing a survival ratio logarithm versus sonication time. RESULTS: Although a significant death rate for E coli was observed with ultrasound treatment, in contrary to expectations, an increase in S aureus populations was observed. CONCLUSIONS: Considering the widespread use of ultrasound for sterilization of tools and equipment used in hospitals, the results obtained in this study indicate that ultrasonic irradiation is not a suitable method for the elimination of the major hospital pathogen S aureus.

Effects of pulsed ultrasound on Escherichia coli and Staphylococcus aureus.

BACKGROUND: Common disinfection methods like biocides, ultraviolet light and heat treatment are not efficient enough to succeed in bacterial inactivation for some microorganisms have become resistant to them. The aim of this study was to obtain information about the effect of pulsed ultrasound sonication with 30 kHz frequency and 100 W power on the inactivation capability of two bacteria groups, namely Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923, in physiological water samples. METHODS: The ultrasonic irradiation of bacterial samples with different populations of 5×10(3), 1.5×10(4) and 3×10(4) cfu/ml was performed at constant frequency with various treatment times. The specific energies (γ) were calculated for these different concentrations of E. coli and S. aureus. The rate constant of ultrasonic inactivation was estimated in the linear region of the plot representing survival ratio logarithm vs sonication time. RESULTS: While a significant death rate for E. coli was observed by ultrasonic treatment, contrary to expectation, an increase in S. aureus populations was observed. CONCLUSIONS: Considering the widespread use of ultrasound for the sterilization of tools and equipment used in hospitals, the obtained results indicate that ultrasound sonication is not a suitable method for the elimination of S. aureus, a major hospital pathogen.