A number of studies have confirmed anti-tumor activity of flavonoids and their ability to enhance the effectiveness of classical anticancer drugs. The mechanism of this phenomenon is difficult to explain because of the ambivalent nature of these compounds. Many therapeutic properties of these compounds are attributed to their antioxidant activity; however, it is known that they can act as oxidants. The aim of this study was to assess the influence of apigenin and hesperidin on MCF-7 breast cancer cells with doxorubicin. The cytotoxic effect was determined using an MTT test and cell cycle analysis. To evaluate the possible interaction mechanism, reduced glutathione levels, as well as the DNA oxidative damage and the double strand breaks, were evaluated. Additionally, mRNA expression of genes related to DNA repair was assessed. It was demonstrated that flavonoids intensified the cytotoxic effect of doxorubicin despite flavonoids reduced oxidative damage caused by the drug. At the same time, the number of double strand breaks significantly increased and expression of tested genes was downregulated. In conclusion, both apigenin and hesperidin enhance the cytotoxic effects of doxorubicin on breast cancer cells, and this phenomenon occurs regardless of oxidative stress but is accompanied by disorders of DNA damage response mechanisms.

Liver diseases, a leading cause of global mortality, necessitate effective dietary strategies. Fermented cereals, traditionally recognized for benefits in glucose regulation, lipid profiles, and antioxidant activity, hold potential for managing conditions such as type 2 diabetes, hypertension, and obesity. However, their specific impact on liver health requires further investigation. Fermentation, particularly solid-state fermentation (SSF), enhances the bioavailability of beneficial compounds, including phenolics. This review summarizes recent studies on the phenolic content of fermented cereals, highlighting variations based on microbial strains and cereal types. It examines the hepatoprotective effects of these phenolics, drawing on in vivo and in vitro research. Furthermore, the review explores recent findings on the impact of fermented cereals on liver health and related diseases. This work provides a foundation for future research exploring fermented cereals as a dietary intervention for liver disease prevention and management.

Macrophages have multiple functions in both inhibiting and promoting hepatocarcinogenesis, which are dependent on their phenotypes. Thus, we were interested in clarifying the ‘training’ proinflammatory effects exerted by barley β-glucan (BBG) on monocyte-derived macrophages from patients with hepatocellular carcinoma (HCC-Mfs). After isolation and differentiation HCC-Mfs were treated with different concentrations of BBG and functional assays were then conducted after 24 h, and 3 and 5 days of incubation. The release of reactive oxygen species, arginase concentration and cell morphology were analyzed. Under the influence of BBG neoplastic cells slightly elongated and dendric-like filopodia were observed. In HCC-Mfs, the significant generation of NO and O₂⁻. was seen on days 3 and 5 of culture, concomitantly with significant depletion (p<0.05) of arginase activity. In summary, we showed that HCC-Mfs, ‘trained’ in a BBG microenvironment keep a highly dynamic plasticity, together with their proinflammatory polarization, expressed by reactive oxygen species and reactive nitrogen intermediates (RNI) augmentation.

Despite the many beneficial properties of legume plants, their use in diets for poultry is limited by the presence of antinutritional factors. The aim of the study was to determine the activity of DT-diaphorase, ethoxycoumarin O-deethylase, and catalase, and the concentration of malondialdehyde in liver tissue, as well as the activity of SOD and CAT in the serum of Hy-line Brown hens fed a diet supplemented with various doses of Lupinus angustifolius seeds. The results indicate that the use of large amounts of lupin in the diet resulted in an increase in MDA concentration in the liver and the lipid vacuolization of hepatocytes. A significant increase in DTD activity was observed in chickens receiving 15% lupin. Regardless of lupin dose, no increase in SOD activity was observed in chicken serum after 33 days of the experiment. From the 66th day of the experiment, an increase in catalase activity in the serum of laying hens was observed, while low activity of this enzyme was found in the liver. It can be concluded that the short-term use of lupin in the diet of laying hens does not affect the activity of antioxidant enzymes and, therefore, does not affect the oxidative–antioxidant balance of their body.

Beer and its components show potential for reducing hepatic steatosis in rodent models through multiple mechanisms. This study aimed to evaluate beer’s anti-steatotic effects in a high-fat diet (HFD)-induced mouse model of Metabolic dysfunction-Associated Liver Disease (MASLD) and to explore the underlying mechanisms. In the HFD group, steatosis was confirmed by altered blood parameters, weight gain, elevated liver lipid content, and histological changes. These markers were normalized in the HFD+beer group, reaching levels similar to the control (CTR) group. Protein carbonylation and lipid peroxidation levels were consistent across all groups, suggesting that the model represents an early stage of MASLD without oxidative stress. Transcriptomic and CpG methylation analyses revealed clear distinctions between the CTR and HFD groups. RNA sequencing identified 162 differentially expressed genes (DEGs) between the CTR and HFD groups, primarily related to inflammation and lipid regulation. Beer consumption modified the health of the HFD mice, affecting inflammation but not lipid homeostasis (CTR vs. HFD+beer, DEGs = 43). The CpG methylation analysis indicated that beer lowered methylation, impacting genes linked to lipid accumulation and inflammation. A cecal metabolite analysis suggested that beer improved short-chain fatty acid metabolism (SCFA). In summary, a moderate beer intake may mitigate MASLD by modulating lipid metabolism and SCFA pathways, likely through polyphenol activity.

Background: Hepatocellular carcinoma (HCC) is highly resistant to conventional therapies, highlighting the need for novel immunotherapeutic approaches. In the tumor microenvironment (TME), the role of proinflammatory M1 macrophages remains ambiguous. The proteins Mapk4/7 and cyclin E2 (CE2, Ccne2) are crucial for regulating hepatocyte proliferation and may be important factors driving the development of HCC. This study aimed to investigate the effects of M1 macrophages on CE2 and Mapk4/7 expression, as well as hepatocyte proliferation, in a rat model of partial hepatectomy (PH) with or without diethylnitrosamine (DEN)-induced HCC. (2) Methods: Twenty female Wistar rats were assigned to nonneoplastic (PH) or neoplastic (PH/DEN) groups. Gene expression (CE2, Mapk4/7) was quantified via real-time PCR. (3) Results: Overexpression of CE2 and increased proliferation were observed in PH/DEN hepatocytes, whereas exposure to proinflammatory M1 macrophages significantly reduced their proliferative activity. Mapk4/7 expression patterns were modulated by the TME and significantly differ depending on macrophage activation status in both PH and PH/DEN-derived hepatocytes. (4) Conclusions: Our findings indicate that CE2 expression is upregulated in PH/DEN cells, with a notable decrease in the presence of M1 macrophages. In contrast, compared with control macrophages, M1 macrophages did not significantly affect Mapk4/7 expression.