Dysregulated ribosome quality control in human diseases.

Precise regulation of mRNA translation is of fundamental importance for maintaining homeostasis. Conversely, dysregulated general or transcript-specific translation, as well as abnormal translation events, have been linked to a multitude of diseases. However, driven by the misconception that the transient nature of mRNAs renders their abnormalities inconsequential, the importance of mechanisms that monitor the quality and fidelity of the translation process has been largely overlooked. In recent years, there has been a dramatic shift in this paradigm, evidenced by several seminal discoveries on the role of a key mechanism in monitoring the quality of mRNA translation - namely, Ribosome Quality Control (RQC) - in the maintenance of homeostasis and the prevention of diseases. Here, we will review recent advances in the field and emphasize the biological significance of the RQC mechanism, particularly its implications in human diseases.

Clitocybe nebularis extract and 5­fluorouracil synergistically inhibit the growth of HT-29 colorectal cancer cells by inducing the S phase arrest.

Although 5-fluorouracil (5-FU) is an important anticancer agent for the treatment of colorectal cancer, drug resistance, and dose-related side effects limit the effectiveness of the treatment. Therefore, developing new pharmaceuticals with effective and low toxicity is critically necessary for cancer therapy. This study aimed to investigate the cytotoxic activity of the Clitocybe nebularis mushroom extract (CN) on HT-29 human colon cancer cells. A series of in vitro experiments were performed on the HT-29, Caco-2, and HEK-293 cells, which includes cytotoxicity, drug interaction, colony formation, cell cycle, and migration assays. In addition, qRT-PCR experiment was also performed to investigate the potential molecular mechanisms of action of CN on the proliferation of colon cancer cell line. Our results show that CN exhibited selective cytotoxic activity on HT-29 and Caco-2 colon cancer cells, whereas no cytotoxic effect was observed on normal HEK-293 cells. With the combination of CN and 5­FU, their cytotoxic activity on HT-29 cells was significantly increased compared to their use alone. In addition, the combination of CN and 5-FU also showed synergistic anticancer activity through cell cycle arrest in the S phase. The results also show that p21, p27, and p53 expression levels increased as a result of CN treatment. Our in vitro findings show that CN has a synergistic effect with 5-FU by inhibiting cell proliferation of colon cancer cells and inducing cell cycle arrest in the S phase.

The Remarkable Antibiofilm Activity of the Sweet Tooth Mushroom, Hydnum repandum (Agaricomycetes), Displaying Synergetic Interactions with Antibiotics.

This study examines the antioxidant, anticancer, antimicrobial, and antibiofilm activities of Hydnum repandum, an edible and medicinal mushroom known as sweet tooth or wood hedgehog. H. repandum ethanolic extract had a high amount of myricetin and apigenin and displayed antiproliferative effects against the MCF-7 and HT-29 cell lines. Moreover, the extract displayed antimicrobial and antibiofilm activities against methicillin-resistant Staphylococcus aureus ATCC 43300, S. epidermidis ATCC 35984, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853. Synergetic interactions have been observed when antibiotics such as kanamycin and ampicillin are used together with mushroom extract. The minimum biofilm eradication concentration values were lower for H. repandum extract than for antibiotics. This study demonstrates that H. repandum has antibiofilm potential against biofilms and confronts antibiotic resistance.

Comparison of the chemical composition and biological effects of Clitocybe nebularis and Infundibulicybe geotropa.

Clitocybe mushrooms have long been recognized for their various therapeutic potential and medicinal properties. A few members of the genus are considered edible and many others are poisonous. This study investigated the ethanolic extracts obtained from C. nebularis (CN) and I. geotropa (IG) mushrooms for phenolic content and antioxidant, antiproliferative, antimicrobial, and antibiofilm activities. The data from ultra-performance liquid chromatography and Fourier transform infrared spectroscopy analysis of the mushrooms were presented for the first time. According to the results, both ethanolic extracts contain high levels of phenolic (catechin, myricetin, quercetin, rutin, gallic acid, vanillic acid) compounds. Fourier transform infrared spectroscopy results may suggest the presence of clitopycin in CN extract. The ethanol extract of CN scavenged about 79% and the IG 78% of the free 2,2-diphenyl-1-picrylhydrazyl radicals. Additionally, the CN and IG extracts inhibited glutathione-S-transferase by 10%-18% at all concentrations. The CN extract effectively inhibited aldose reductase by 30%-80% at all concentrations. Besides, the CN extract showed promising antiproliferative activity on HT-29 and MCF-7 cell lines. On the other hand, CN and IG extracts displayed inhibitory effects on some multidrug-resistant Gram-positive bacteria and effectively inhibited biofilm production. The obtained results showed that C. nebularis and I. geotropa extracts presented inhibition of biofilm production. Therefore, C. nebularis was demonstrated to be a potential source of natural medicine.

Antioxidant, Anticancer, Antimicrobial, and Antibiofilm Properties of the Culinary-Medicinal Fairy Ring Mushroom, Marasmius oreades (Agaricomycetes).

This study is based on the phenolic composition and the antioxidant, anticancer, antimicrobial, and antibiofilm activities of the edible mushroom Marasmius oreades from Turkey. The phenolic composition of an M. oreades ethanol extract was measured by using the Folin-Ciocalteu method, aluminium chloride colorimetry, and ultraperformance liquid chromatography. The antioxidant activity was evaluated on the basis of DPPH radical scavenging activity. The effect of the M. oreades ethanol extract was also screened in order to determine glutathione-S-transferase, glutathione peroxidase, catalase, and superoxide dismutase enzyme activities. The antimicrobial activity of the mushroom extract was evaluated by using well diffusion and was based on the minimum inhibitory concentration. In addition, the antibiofilm potential of M. oreades was analyzed against Gram-positive and -negative bacteria. Finally, the anticancer effects of the mushroom extract were tested on colon (HT-29) and breast (MCF-7 and MDA-MB-231) cancer cell lines by using the MTT assay. The results revealed that the total amount of phenolics in the ethanol extract of M. oreades was 10.990 ± 0.0007 mg gallic acid equivalent/100 g, and the total amount of flavonoids was 1.139 ± 0.0052 mg quercetin equivalent/100 g. The ultraperformance liquid chromatography results indicated that the M. oreades ethanol extract contained various phenolic compounds: catechin, ferulic, gallic acid, and vanillic acid. The M. oreades ethanol extract scavenged about 80% of DPPH free radicals. It did not show any effect on the glutathione-S-transferase, glutathione peroxidase, and catalase enzyme activities, but its maximal concentration (10 mg/mL) increased superoxide dismutase activity (8%). The ethanol extract of M. oreades showed a moderate anticancer effect on the HT-29, MCF-7, and MDA-MB-231 cell lines. Although the ethanolic extract of the mushroom did not show sufficient antibacterial activity, it presented a strong antibiofilm effect against all studied pathogenic strains at the tested concentrations.

Investigation of the Polyphenol Composition, Biological Activities, and Detoxification Properties of Some Medicinal Mushrooms from Turkey.

OBJECTIVES: Ethanolic extracts of the mushroom species Ganoderma adspersum, Inonotus hispidus, Russula chloroides, and Sarcodon imbricatus were investigated for their polyphenolic contents and biological activities. MATERIALS AND METHODS: The radical scavenging activity of the extracts was evaluated by 2,2-diphenyl-1-(2,4,6-trinitrophenyl) (DPPH) method and their polyphenolic compounds were determined by high performance liquid chromatography (HPLC) analysis. Furthermore, the activity effects of mushroom extracts on the enzyme glutathione-S-transferase (GST) were also examined. Additionally, the antimicrobial activity of mushroom extracts was evaluated by disc diffusion method. RESULTS: Ethanolic extract of I. hispidus demonstrated the highest total phenolic content and total flavonoid contents, with 227.23±4.96 mg gallic acid equivalent/g and 42.14±0.20 quercetin equivalent/g, respectively. The highest DPPH radical scavenging activity was observed for ethanolic extracts of I. hispidus, with 10.687±1.643 µg/mL IC50. HPLC analysis demonstrated that R. chloroides was composed of ferulic acid, gallic acid, and myricetin compounds. The highest GST enzyme activity effect was detected with the ethanol extracts of I. hispidus and S. imbricatus. None of the mushroom extracts demonstrated significant inhibition of the bacterial strains used. CONCLUSION: These results indicate that I. hispidus may be proposed as a new potential source of natural medicine and its potential may be related to its polyphenolic content, which needs further investigation.