Molecular Biology Reports最新文献

Background: This study aimed to investigate the anticancer effects of lobaric acid (LA), a lichen acid, in MCF-7 cells. Our previous study demonstrated that LA exhibits anticancer effects by triggering apoptosis in MCF-7 cells. However, the relationship between this anticancer effect and the oxidative pathway and apoptosis mechanism has not been explained. In this study, the cytotoxic and anticancer effects of LA on MCF-7 cells were investigated through oxidative stress and thioredoxin system pathways.

Methods and results: For this purpose, reactive oxygen species (ROS), reduced glutathione (GSH), and malondialdehyde (MDA) levels were measured in MCF-7 cells exposed to LA at a concentration of 44.21 µg/mL (IC50). Additionally, the activities, gene, and protein levels of SOD, CAT, GPx, GST, GR, and TrxR enzymes were evaluated. In addition, the expression levels of TXN and TXNIP genes were also analyzed. The results showed that LA increased ROS and MDA levels and decreased GSH levels. Antioxidant enzyme activities (SOD, CAT, GR, TrxR) and protein levels decreased compared to the control, while heterogeneous changes were observed in gene expression levels. Despite increased GPX gene expression, a decrease in enzyme activity and protein levels was observed. While no change in TXN gene expression was observed, protein levels were decreased. TXNIP protein levels were also decreased.

Conclusions: The findings provide important data for evaluating lichen-derived compounds as potential anticancer agents targeting redox balance.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with limited efficacy of current therapies and frequent drug resistance. Cocoa pod husk (CPH), an abundant agro-industrial by-product, is rich in bioactive compounds but remains underutilized. This study investigated the anti-HCC potential of CPH using integrated green extraction, in silico prediction, and in vitro validation.

Methods: CPH extracts were prepared via ultrasound-assisted extraction (CPH-UE) and enzymatic extraction (CPH-EE). Phytochemical profiling was conducted using UHPLC-ESI-HRMS/MS. In silico analyses included structure-activity relationship prediction, ADMET profiling, network pharmacology, and molecular docking against key HCC targets (EGFR, PIK3CA, and SRC). Anticancer activity was evaluated in HepG2 and Huh7 cell lines using MTT assays, with THLE-2 normal liver cells as control.

Results: CPH-UE was enriched in polyphenols (catechin, epicatechin, quercetin), whereas CPH-EE contained bioactive peptides and procyanidin B2. In silico analyses highlighted EGFR, PIK3CA, and SRC as central targets, with favorable binding affinities for major polyphenols. In vitro assays demonstrated dose-dependent antiproliferative effects, with CPH-UE showing lower IC₅₀ values and better selectivity toward HCC cells than CPH-EE.

Conclusion: Cocoa pod husk exhibits promising anti-HCC activity through multi-component, multi-target mechanisms. Ultrasound-assisted extraction yields polyphenol-rich extracts with superior anticancer potency, supporting CPH valorization as a sustainable source of functional anticancer agents.

Background: Acrylamide (ACR) is an environmental and dietary contaminant widely known to induce imbalance in several biological systems, including oxidative stress, inflammation, and metabolic dysregulation. This study investigated the protective effects of gypenosides (GYP) against ACR-induced toxicity in human retinal pigment epithelial (RPE) cells and zebrafish embryos.

Methods and results: RPE cells and zebrafish embryos were treated with ACR, or ACR + GYP; the levels of reactive oxygen species (ROS), antioxidative enzymes, proinflammatory cytokines, and lipids were measured using biochemical approaches. Our findings demonstrate that ACR exposure significantly elevated ROS production, increased lipid peroxidation, suppressed antioxidant defences, and upregulated pro-inflammatory cytokines in RPE cells. Additionally, ACR disrupted lipid metabolism, significantly increasing cellular cholesterol, triglyceride, and phospholipid levels while altering cholesterol metabolism gene expression. Co-treatment with GYP effectively mitigated ACR-induced oxidative stress by normalising ROS levels, restoring antioxidant enzyme activities, and upregulating antioxidant gene expression. GYP also attenuated the ACR-triggered inflammatory response, significantly downregulating the expression of proinflammatory cytokine genes. Furthermore, GYP normalised lipid profiles and modulated lipid-related gene expression disrupted by ACR exposure. Parallel zebrafish experiments corroborated these protective effects. ACR exposure led to delayed hatching, impaired cardiac function, increased ROS production, and neutral lipid accumulation. These adverse effects were markedly ameliorated by GYP co-treatment, which reduced oxidative stress, downregulated proinflammatory markers, and restored lipid homeostasis.

Conclusion: The results highlighted that GYP, as a natural protective agent against ACR-induced cellular and metabolic toxicity in both in vitro and in vivo models, exhibited antioxidative, anti-inflammatory, and lipid-regulatory properties.

Background: N6-methyladenosine (m6A) modification of mRNAs through METTL3 maintains homeostasis in many cell types. The mechanism by which METTL3 complexes together with reader proteins, especially the YTH domain-containing protein, governs endothelial homeostasis is not yet fully understood.

Methods and results: Primary endothelial cells (HUVECs), EA.hy926 cells, and rat aortas were used to modulate METTL3 activity and assess gene expression changes by molecular and biochemical assays. m6A RNA immunoprecipitation and RNA-protein interaction analyses were performed to determine transcript-specific m6A modification and YTHDF-mediated regulation. Interplaying with METTL3 caused abrupt yet selective loss of eNOS gene expression while increasing inflammatory adhesion molecule gene expression in cultured endothelial cells (EC) and rat aorta. Interestingly, many other genes associated with endothelial function/inflammation/senescence including CD31, CD144, KLF2, p65, and p53 remained unaltered upon METTL3 inhbition. MeRIP analysis revealed significant m6A modifications of several gene transcript including eNOS, and inflammatory adhesion molecules. m6A modification of gene transcripts selectively stabilized eNOS while causing degradation of inflammatory adhesion molecules without affecting the stability of other genes such as p65. Interestingly, RIP analysis showed that YTHDF1 was preferentially bound to m6A-modified eNOS while YTHDF2 was selectively associated with inflammatory adhesion molecules, causing differential regulation. Moreover, we failed to detect association of YTHDF1 or YTHDF2 to m6A modified p65 and KLF2 transcript.

Conclusion: Taken together, the current study describes the essential role of the METTL3 complex in maintaining endothelial homeostasis through differential association of m6A modified gene transcripts with the reader proteins.