Background: The goal of research was to investigate the possible relations between serum concentrations of IL-6 and TGF-β1, individual and clinical characteristics, and adverse effects of radiotherapy in patients with prostate cancer: acute and late genitourinary and gastrointestinal toxicity, and fatigue. Methods: Thirty-nine patients with localized or locally advanced prostate cancer who were treated with radiotherapy were enrolled in this study. The acute radiotoxicity grades and fatigue levels were assessed during the radiotherapy and 1 month after the radiotherapy. Estimation of the late radiotoxicity was performed every three months in the first year, every four months in the second year, and then every six months. Serum levels of IL-6 and TGF-β1 were determined before radiotherapy and after the 25^th radiotherapy fraction by ELISA. Results: The significant positive association between diabetes mellitus and changes in acute genitourinary toxicity grades during the radiotherapy was observed in prostate cancer patients. In addition, patients who were smokers had significantly higher maximum fatigue levels in comparison with patients who were non-smokers. The circulating IL-6 levels were significantly higher after the 25^th radiotherapy fraction in comparison with levels determined before radiotherapy. The significant positive correlations between pretreatment TGF-β1 levels and maximum genitourinary toxicity grades and between TGF-β1 levels after the 25^th fraction and genitourinary toxicity grades after the 25^th fraction, were found. The pretreatment IL-6 concentrations and TGF-β1 concentrations after the 25^th fraction were positively correlated with maximum genitourinary toxicity grades. The IL-6 levels after the 25^th fraction were positively associated with genitourinary toxicity grades after this fraction. The pretreatment IL-6 concentrations were significantly positively correlated with maximum fatigue scores. The significant positive correlation between IL-6 concentrations and fatigue scores after the 25^th fraction was determined. The positive correlations between IL-6 and TGF-β1 concentrations measured after the 25^th fraction and maximum fatigue scores were observed. Conclusions: Our results suggest that serum levels of IL-6 and TGF-β1 might influence the severity of acute genitourinary radiotoxicity and fatigue in patients with prostate cancer. Combining clinical parameters and circulating cytokine levels might be useful for the prediction of adverse reactions to radiotherapy.

In this paper, the synthesis, characterization, and biological evaluation of the novel tetrahydropyrimidines—THPMs are described. THPMs are well-known for wide pharmacological activities such as antimicrobial, anticancer, antiviral, etc. This research includes obtained results of in vitro antimicrobial, anticancer, and α-glucosidase inhibitory activities of the eleven novel THPMs. An antibiotic assessment was done against five bacteria (two Gram-positive and three Gram-negative) and five fungi by determining the minimal inhibitory concentration (MIC), using the broth tube dilution method. The most active antibacterial compounds were 4a, 4b, and 4d, while the best antifungal activity was shown by 4e, 4f, and 4k. The lowest MIC value (0.20 mg/mL) was measured for 4e, 4f, and 4k against the Trichophyton mentagrophytes. Moreover, examining the α-glucosidase inhibitory activity revealed the compound 4g as the one with the best activity. The cytotoxic activity was performed on the tumor cell lines (HeLa, K562, and MDA-MB-231) and normal cells (MRC-5). The best antitumor activity was shown by compounds 4b and 4k against HeLa cell lines. The influence on cell cycle and mechanism of action of the most active compounds were examined too. Compound 4b had good antibacterial and anticancer activities, while 4k showed promising antifungal and anticancer activities.

Cotinus coggygria has a long history of use in traditional medicine in Europe and Asia. The aim of study was to explore the cytotoxicity of extracts (EE-ethanol, MME-methylene chloride/methanol, and WE-water) and compounds (butin, butein, fisetin, sulfuretin, taxifolin, eriodictyol, fustin, cotinignan A, sulfuretin auronol, 3-O-methylepifustin, 3-O-methylfustin, and sitosterol-3-O-β-D-glucoside) isolated from C. coggygria. Mechanisms of anticancer effects of three extracts, butin, butein, and sulfuretin were examined. Compounds were isolated from the EE using silica gel column chromatography and semipreparative HPLC. Structure elucidation was performed using NMR spectroscopy. Cytotoxicity was evaluated using MTT assay. The effects on cell cycle and cell death were investigated by flow cytometry. The antimigration effects were examined by scratch assay, while expression of the MMP2, MMP9, and VEGFA were measured by quantitative real time PCR. The antioxidant effects were examined by flow cytometry. 3-O-methylepifustin, epitaxifolin, and sulfuretin auronol were found for the first time in C. coggygria. The extracts and compounds showed selective cytotoxicity against HeLa, MDA-MB-231, HL-60, K562, A375, PC-3, and DU 145 cells. HeLa cells were the most sensitive to the cytotoxicity of MME (IC50 value of 47.45 µg/mL), while leukemia K562 and HL-60 cells were the most sensitive to the MME and EE (IC50 values in the range from 31.04 to 44.57 µg/mL). Butein exerted strong cytotoxicity on HeLa, K562, and MDA-MB-231 cells (IC50 values of 8.66 µM, 13.91 µM, and 22.36 µM). EE, butin, butein, sulfuretin, and fisetin were highly selective against leukemia K562 cells when compared with normal fibroblasts MRC-5 (selectivity index: 4.01, 5.15, 6.17, 7.05, > 4.41, respectively). Butein and fisetin showed high selectivity in the cytotoxic activity against HeLa cells when compared with MRC-5 cells (selectivity index: 9.91 and > 6.61). Three extracts, butin, butein, and sulfuretin, initiated apoptosis in HeLa cells by activating caspase-8 and caspase-9. The extracts, butin, butein, and sulfuretin inhibited HeLa cell migration. EE, MME, butein, and sulfuretin exerted cytoprotective effects in normal fibroblasts. This research might suggest promising anticancer effects and underscores the need for additional research on C. coggygria extracts and compounds to assess their potential in cancer prevention and therapy.

Mahonia aquifolium and its secondary metabolites have been shown to have anticancer potential. We performed MTT, scratch, and colony formation assays; analyzed cell cycle phase distribution and doxorubicin uptake and retention with flow cytometry; and detected alterations in the expression of genes involved in the formation of cell–cell interactions and migration using quantitative real-time PCR following treatment of lung adenocarcinoma cells with doxorubicin, M. aquifolium extracts, or their combination. MTT assay results suggested strong synergistic effects of the combined treatments, and their application led to an increase in cell numbers in the subG1 phase of the cell cycle. Both extracts were shown to prolong doxorubicin retention time in cancer cells, while the application of doxorubicin/extract combination led to a decrease in MMP9 expression. Furthermore, cells treated with doxorubicin/extract combinations were shown to have lower migratory and colony formation potentials than untreated cells or cells treated with doxorubicin alone. The obtained results suggest that nontoxic M. aquifolium extracts can enhance the activity of doxorubicin, thus potentially allowing the application of lower doxorubicin doses in vivo, which may decrease its toxic effects in normal tissues.

Prostate cancer is one of the most prevalent malignancies in men, posing a significant public health challenge due to its high incidence and long-term treatment-related toxicities. Long-lived patients often experience prolonged side effects that can severely diminish their quality of life. Despite advancements in radiotherapy techniques like IMRT and VMAT, some patients still experience acute and late side effects. Current treatment protocols do not account for individual variability in normal-tissue radiosensitivity, highlighting the need for predictive tools and a personalised treatment approach. Genetic factors and molecular regulators like microRNAs (miRNAs) contribute to these variations by influencing DNA repair, inflammation, and apoptosis. This review explores potential biomarkers of radiotoxicity, focusing on immune-related factors such as IL-6 and TGF-β1, SNPs influencing radiosensitivity, miRNAs involved in radiation responses, and functional assays including the radiation-induced lymphocyte apoptosis (RILA) test. These approaches offer promising tools for identifying radiosensitive patients and enabling risk-adapted radiotherapy.