Balkan Medical Journal最新文献

Background: In uremic patients, the accumulation of gut-derived protein-bound uremic toxins (PBUTs) induces changes in the microenvironment of the patients, leading to changes in the elimination pattern of drugs.

Aims: To assess ways in which PBUTs alter the CYP450 enzymes in hepatocytes as well as the possible effects of specific PBUTs on the metabolism and excretion of atorvastatin (ATV).

Study design: An experimental study.

Methods: The experimental group was treated with long-term MHD for > 3 months, estimated-glomerular filtration rate (e-GFR) < 15 ml/min, normal Alb level (35.0-55.0 g/l), and no urine; the control group was not treated with hemodialysis, e-GFR < 60 ml/min, normal Alb level, and normal urinary excretion function. A suitable UPLC-MS/MS method was developed for detecting the concentration of 4-hydroxy ATV. Fresh primary hepatocytes were isolated from rats, and the uptake of ATV was tested in the uremic serum (US) group, IS group, and HA group and compared with that in the normal serum group. The metabolic status of ATV in the US group, IS group, and HA group was compared with that in the ATV group. RLM were extracted, and the metabolic experiment of ATV was performed in a human CYP3A4 model. The influence of UTs on pregnane X receptor (PXR)/nuclear factor kappa B (NF-κB) mRNA and the protein expression was also detected.

Results: IS and HA inhibited the ATV metabolism to varying degrees, wherein IS was the most potent inhibitor, producing > 50% inhibition. Meanwhile, the protein expression of CYP3A4 was downregulated after incubation with US, IS, and HA (p < 0.01). The excretion of ATV was also inhibited by 59.24% and 71.95% after incubation with IS and HA, respectively. The effects of uremic toxins on PXR/NF-κB mRNA and protein expression elucidated that PBUTs can inhibit ATV uptake and metabolism by exerting inhibitory effects on CYP3A4 through the PXR/NF-κB signaling pathway.

Conclusion: ATV metabolism could be significantly altered in the presence of uremic toxins, suggesting a downregulated effect on the ATV uptake, possibly through Oatp1b1, and also on the activity of CYP3A4 through the PXR/NF-κB signaling pathway.

Background: Postoperative nutritional support in gastrointestinal cancer, including enteral nutrition (EN), parenteral nutrition (PN), and combined nutrition strategies, is vital for enhancing recovery and patient outcomes.

Aims: We aimed to comprehensively evaluate the impact of postoperative EN, PN, and EN + PN in patients with gastrointestinal cancer.

Methods: PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wan Fang, and VIP were searched from conception until January 2, 2024. Randomized controlled trials (RCTs) that compared different postoperative nutritional support (EN, PN, or EN + PN) in patients with gastrointestinal cancer were included. The Cochrane Risk of Bias Assessment tool was used to assess the quality of the RCTs. Fixed- and random-effects models were chosen according to the heterogeneity of variables for the synthesis of results. Continuous and categorical variables were analyzed using the weighted mean difference or relative risk (RR) and 95% confidence interval (CI).

Results: In this meta-analysis, 11 RCTs were included. The PN + EN group exhibited significantly improved postoperative recovery, nutritional function, and immune indicators than the PN and EN groups (p < 0.05). Additionally, a higher incidence of postoperative complications such as abdominal distension (RR: 2.53; 95% CI: 1.17-5.49), nausea/vomiting (RR: 2.01; 95% CI: 1.09-3.71), and diarrhea (RR: 3.17; 95% CI: 1.41-7.10) was observed in the EN group than in the PN + EN group.

Conclusion: Combining supplemental PN with enteral support improves energy intake and prognosis in gastrointestinal cancer, though limited studies restrict publication bias evaluation.

Background: Breast cancer (BC) is the most prevalent solid cancer affecting women's health globally. Matrine (MAT), a traditional Chinese herb, has exhibited antitumor effects against BC. However, its mechanism of action, particularly whether it involves the control of cell proliferation and epithelial-mesenchymal transition (EMT), remains unknown.

Aims: To explore MAT's role in BC and its regulatory mechanisms, as well as to identify targets for the development of novel medicines and improvement of BC treatment modalities.

Study design: Experimental study.

Methods: The UALCAN and Lnc2Cancer 3.0 databases were used to predict the expression of LINC01116 in BC. The BC cells (MDA-MB-231 and MCF-7) were treated with various concentrations of MAT, and the optimal dose and timing of MAT action were determined using CCK-8 and quantitative real-time polymerase chain reaction assays. Functional assays such as CCK-8, EdU, Transwell, Western blot, and flow cytometry assays were performed on the BC cells, and the impacts of LINC01116, miR-9-5p, and ITGB1 expression levels on MAT's mechanism of action were assessed. The association between LINC01116, miR-9-5p, and ITGB1 was evaluated using dual luciferase and RNA immunoprecipitation assays. Furthermore, the size and weight of the subcutaneous tumors in mice model were assessed. The effect of LINC01116 overexpression on the in vivo action of MAT and histopathological staining (TUNEL immunofluorescence, hematoxylin & eosin staining, immunohistochemistry staining for Ki67 and Bax) were also assessed.

Results: The optimal dose and duration of MAT administration were 8 μm and 24 h, respectively. MAT effectively inhibited BC cell proliferation, EMT progression, and biological functions, while promoting BC cell apoptosis. The animal model experiments also demonstrated that MAT inhibited BC tumor growth in vivo. Furthermore, MAT inhibited LINC01116, which acted as a sponge for miR-9-5p, increasing the ITGB1 level.

Conclusion: MAT suppresses BC cell and EMT proliferation via the LINC01116/miR-9-5p/ITGB1 pathway. Thus, MAT may be a promising target for adjuvant anti-BC therapy.